Podcasts about Ticagrelor

Kiera is joined by the tooth-healer himself, Jason Dent! Jason has an extensive background in pharmacy, and shares with Kiera where his pharmaceutical experience has bled over into dentistry. This includes the difference between anti-quag and anti-platelet and which medications are probably safe, what to do to shorten the drag time in the pharmacy, how to write prescriptions most efficiently, and more. Episode resources: Subscribe to The Dental A-Team podcast Schedule a Practice Assessment Leave us a review Transcript: The Dental A Team (00:00) Hello, Dental A Team listeners. This is Kiera and today is a really awesome and unique day. It is, think the second time I've had somebody in the podcast studio with me live for a podcast and it's the one and only Jason Dent. Jason, how are you? I'm doing well. Good morning. Thanks for having me. It is crazy. I I watch Instagram real like this all the time where people are like in the podcast and they're hanging out on two chairs and couches and now look at us. We're doing it. Cheers. Cheers.   That was a mic cheer for those of you who are only listening, but yeah, Jace, how does this feel to be on the podcast? It's weird. Like I was not nervous at all talking about it. I got really nervous as soon as you hit play. So if I stumble over my words, please forgive me ahead of time. Well, Jason, I appreciate you being on the podcast because marketing had asked me to do a topic about teledentistry and I was like, oh shoot, that's like not my forte at all. so   You and I were actually chatting in the hot tub. call it Think Tank session and you and I, we have a lot of good ideas that come from that Think Tank. A lot of business. no phones. That's why. We do leave our phones out. But I was talking to Jason and this is actually a podcast we had talked about quite a while ago. Jason has a lot of information on pharmacy. And if you don't know, Jason isn't really, we were going through all of it last night. It's kind of a mock in the tub. And I think it's going to be great because I feel like this is an area, I'm working at Midwestern and   knowing about how dentists, pharmacology was surely not your favorite one. Jason actually helps a lot of dentists with their clearances. And so we were talking about it and I like it will just be a really awesome podcast for you guys to brush up on pharmacology, different things from a pharmacist's side. So Jason, welcome. Thank you. Yeah, no, we were talking about it and here's like, what should I talk about on the podcast next? I have all these different topics and she's like, what do you know? And the only real interaction I have with dentists is doing clearances for procedures. We get them all the time, which makes sense.   Lots of people are on blood thinner, I've always told Kiera, like, hey, I could talk about that. Like, that's kind of a passion of mine. I'm not a dentist. Or my name is Jason Dent. So in Hebrew, Jason means tooth. No, no, no, sorry. Nerves are getting to me. Jason means healer and Dent means tooth. So my name means tooth healer. So, here's a little set. Hold on, on, hold Can we just talk about? I brought that up before you could talk about it more. So.   My name means tooth healer but I did not become a dentist. I know you wanted me to become a dentist. did. I don't know why. I enjoy medicine. I know what you're going to get to already. The things you're going to ask me. There's been years of this. But nevertheless, that's my name. We'll get that out of the way. But you did give me a great last name. So I mean, it's OK. You're All is fair and love here. SEO's up for that. But yeah, Jason, I'm going to get you right into the show. And I'm going to be the host. And we're going to welcome to the podcast show. Jace, how are you?   Good, good, good. Good, good, good. So by getting into clearances, right? This is what you're kinda talking about with you know, before we get to clearances, I actually wanted Jason, for the listeners who don't know you, who haven't talked to you, who don't know, let's kinda just give them like, how did you go from, Kiera wanted you to be a dentist, to now Jason, you are on the podcast talking as our expert on pharmacy. fantastic. I've always really loved medicine, a ton. As a kid getting headaches and taking Excedrin, like you just feel like a miserable pile of crap.   and then you take two pills and all of a sudden you feel better. Like that's amazing, like how does that happen? Also getting ear aches as a kid, just being in so much pain and then taking some medicine and you start feeling a lot better. I always had a lot of appreciation for that. I've always been mechanically inclined. I went to, started doing my undergrad and took biology and learned about ATP synthase, which is a spinning enzyme that's inside the mitochondria, like a turbine engine. I used to work on small engines on my dirt bike and thought that is so cool. So I really got wrapped up into chemistry.   All the mechanics of chemistry really pulled me in. I'm not getting goosebumps. checking. I usually get goosebumps when I think about chemistry. But it's so cool. You think an engine's awesome, like pistons and camshafts and pressures, the cell is the same thing. It's not as loud, so it's not as cool. But it's fascinating. that's why we're like. ⁓   chemistry and really got into coagulation. So I did my residency after pharmacy school. we went to Arizona for three years. ⁓ You did and your main focus, you were never wanting to be the guy behind the counter. No, I haven't done that. Yeah. No, I love them though. I've always really want to go clinical. ⁓ But I love my retail ⁓ pharmacists. They're amazing resources. And ⁓ I use the retail pharmacist every day still to this day, but I went more the clinical route, really love the chemistry aspect of it.   did my doctorate degree and then I did my residency in Reno. Reno's kind That's how we got here everybody. Welcome to Reno. Strategically placed because I was really interested in critical medicine and where we're located we cover a huge area. So we pull in to almost clear, we go clear to Utah, clear to California, all of Northern Nevada. We get cases from all over. So we actually are kind like the first hub of care for lot of areas. So we really get an eclectic mixture of patients that come in that need-   all kinds of different cases that are coming to them. So it's what I really wanted. So I did my residency in critical care there. And then for the next 10 years, I worked in vascular medicine with my final five years being the supervisor of the clinic. Ran all the ins and outs of that. So my providers, two doctors were on our view. So when we talk about dentistry, talk about production, those kinds of things, totally get it. My doctors were the exact same way, my vascular providers. ⁓   There's some pains there, right? You wanna be seeing patients as much as possible, being able to help as many people, keeping the billing up. And had other nurse practitioners, four practitioners, a fleet of MAs, eight pharmacists. We also had that one location we had, going off the top of my head, I think we had eight locations running as well. And we took care of all the different kinds of vascular cases that came to us. Most common was blood clots, ⁓ which is just a...   which is an easier way of saying VTE. There's so many different ways to say a blood clot. Like you might hear patients say, I've had a PE or a DVT or a venous thromboembolism or a clot in my leg, right? They're all clots, but in different locations. Same with an MI, and MI can be a clot as well. ⁓ there's a lot of, everybody's kind of saying the same thing, but sometimes the nomenclature can make it sound hard, but it really is actually pretty simple.   No. And Jason, I love that you went through, you've been in like, and even in your, ⁓ when you were getting your doctorate, you were in the ER. You also worked in retail pharmacy. remember you having a little sticker on your hand. And retail pharmacy, I have a lot of respect for those guys. They have a lot of pressure on them. and then you also, ⁓ what was that test that you had to take that? I don't know. You were like studying forever for it. ⁓ board certification for, ⁓ NABP. Yeah. So I did that board certification as well.   And now you've moved out of the hospital side onto another section in your career. Now in the insurance, right? So it's really, really interesting. So now I'm on the other side reading notes and evaluating clinical appropriateness and trying to help patients with getting coverage and making those kinds of determinations. So yeah, I've really jumped all over. Really love my clinical days. I know. don't I don't I do miss them. But yeah, kind of had a good exposure to a lot of.   pharmacy a lot a lot of dentists actually with all the places that come through which Jason I really appreciate that and honestly I know you are my spouse and so it's fun to have you on but when I go into conversations like this I don't know any of this information and so finding experts and Jason I think here's me talk more about dentistry and my business than I do hear about him on pharmacy so as we were chatting about this I really realized you are a wealth of knowledge because you've been on the clinical side so you've done a lot of patient care and you've seen how   medications interact and I know you've had a few scares in your career and ⁓ you've known some physicians that have had a few scares and ⁓ you've seen plenty of patients pass away working in the ER and gosh in Arizona drownings were such a big deal. I remember when you were in the ER on your rotations I'd be like who died today? Like tell me the stories and you've really seen and now going on to the insurance side I felt like you could just be such a good wealth of knowledge because I know dentists are sometimes so   I would say like maybe just a little more anxious when it comes to medications. I know that dental students from Midwestern were like here was like four months and we had to like pass it, learn it. And Jason, you've done four years plus clinical residency, plus you've been in it. And something I really love about Nevada Medicine is they've been so collaborative with you.   like your heart, your cardiologist, they diagnose and then they send to you to treat with medicine and... Yeah, I've been really lucky being here in Reno too. The cardiology team has been amazing to work with. We started a CHF program, sorry, congestive heart failure program for patients. So we would collaborate with cardiologists. They'd see the cardiologists and then they send them to the pharmacist to really manage all the medications. So there's pillars of therapy ⁓ called guideline directed medical therapy and the pharmacist would take care of all that. So that's gonna be your...   your beta blockers, your ACEs, your ARBs, your Entresto, which would be a little bit better, spironolactone. So just making sure that all these things are dosed appropriately, really monitoring the heart, and make sure that patients are getting better. we've had real positive outcomes when the, sorry, this is totally off topic. do, talk about that study. When we looked at when patients were coming to see our pharmacists in our clinic that we started up, the patients were half as likely to be readmitted. And this was in 2018, and our pharmacists,   We're thinking about all the medications. We're usually adjusting diabetes medications too at the same time. Just kind of naturally just taking care of all the medications because we kind of got a go ahead from the providers, a collaborative practice agreement that we could make adjustments to certain medications within certain parameters. So we weren't going rogue or maverick, but we were definitely trying to optimize our medications as much as possible. And then years later, some studies came out with, I'm sure you've seen Jardins and Farseegh. not trying to, I'm not.   I don't get any kickback from them. I have no conflicts to share. But because our pharmacists were really optimizing that medication, those medications were later shown to reduce hospitalizations and heart failure, even though they're diabetes medications. Fascinating. So it wasn't really the pharmacists. It was just the pharmacists doing as much as they can with all the tools that were in front of them. And then we found out that the patients were going back to the hospital.   half as much as regular patients. So, yeah, being here, it's been so amazing to work with providers here. the providers here want help, want to help patients, don't have an ego. I mean, I just, it's awesome. I love it. I do love how much I think Jason sees me geek out about dentistry and I watching Jay's geek about his pharmacy and how much he loves helping patients. And ⁓ really that was the whole idea of, all right.   Dentistry has pharmacy as a part of it. And I know a lot of dentists are sending in clearances and I know working in a chair side, it would be like, oh no, if they're on warfarin or on their own blood clot, you guys, honestly don't even know half of what I'm talking about because this is not my jam, which is why Jason's here. But I do know that there was always like, well, we got to talk with their provider. And so having Jason come in and just kind of explain being the pharmacist that is approving or denying or saying yes or no to take them off the blood thinners in different parts, because you have seen several dental   I don't know what they're called. What is it? Clarence's? that what comes to you? don't even know. All day my mind, it's like, here is the piece of paper that gets mailed to you to the pharmacist and then you mail it back. So whatever that is. But Chase, let's talk about it because I think you can give the dentist a lot of confidence coming from a pharmacist. What you guys see on that side. When do you actually need to approve or disapprove? Let's kind of dig into that. Yeah. Well, first of all, I think I'm not a replacement for any kind of clinical judgment whatsoever. Every patient's different. But the American Diabetes Association, you   I work with diabetes a lot. American Dental Association has some really great guidelines on blood thinners and I would always reference them. I actually looked at their website today. Make sure I'm up to speed before I get back on this again. They have resources all around making decisions for blood thinners. And I think the one real important thing in putting myself in the shoes of a dentist or any kind of staff that's around a patient that's in a chair, if they say I'm on a blood thinner, right, a flag goes up. At least in my mind, that's what goes up.   Like, okay, how do we get across this bridge? And I think the important thing to really distinct right then when they say they're on a blood thinner is that is kind of a slang word for a lot of different medications, right? Like it's the overarching word that everybody pulls up saying, I'm on a blood thinner. It's like, okay, but I don't know what say. It's like, I have a car. You're like, okay, do you have a Mazda? Do you have?   Toyota, Honda, what do you have? or even worse it'd be like saying I have a vehicle, right? So when somebody says they're on a blood thinner, it opens up a whole box of possibilities of what they're Blood thinners are also, doesn't, when they're taking these types of medications that are quote unquote a blood thinner, it doesn't actually thin the blood, like adding water to the blood, if that makes sense, or like thinning paint, or like thinning out a gravy, right? It doesn't do the same thing. Blood thinners, really what they're doing is they're working on the blood, which.   which is really cool, try not to tangent on that. ⁓ When they're working on the blood, it's not thinning it per se, but it's making it so that the proteins or platelets that are in it can't stick together and make a cloth quite as easy. So whenever somebody's on a blood thinner, I usually ask, what's the name of the blood thinner that you're on? It's not bad that they use that slang, that's okay, on the same page, but it's really broken into two different classes. There's anticoagulant and antiplatelet.   And a way to kind of remember which is which, when residents would come through our clinics, the way that I teach them is a clot is like a brick wall. You know, it's not always a brick wall. Usually the blood is a liquid going through. But once they receive some kind of chemical message, it starts making a brick wall with the mortar, which is the concrete between the and the bricks, the two parts. When it's an anti-quagent, it's working on that mortar part. When it's an anti-platelet, it's working on the bricks part, right? You need both to make a strong clot or strong brick wall.   But if you can make one of them not work, obviously like if your mortar is just water, it's not working, right? You're not gonna make a strong brick wall. So that's kind of the two deviants right there. So that's what I do in my mind real quickly to find out because antiplatelets are usually, so that's gonna be like your Plavix, Ticagrelor, Brilinta. And hold on, antiplatelets are bricks? Good job, bricks. They're the bricks. And so the reason I was thinking you could remember this because I'm, antiplatelets, it's a plate and a plate is more like a brick.   And anti coagulant, I don't know why quag feels like mortar to me, like quag, like, know, it's like slushy in the blood, like it's coagulating. It's a little bit of that, like, honestly, I'm just thinking like coagulated blood is a little bit more mortar-ish. And so platelet is your plate, like a brick, and anti-quag is like.   the gilly between the bricks. Okay, okay, I got it. Yeah, so there's an exception to every rule, but when they're on that Don't worry, this is Kiera, just like very basic. You guys are way smarter listening to this, and that's why Jason's here. No, no, you helped me pass pharmacy school. When we were doing all the top 200, you helped me memorize all know what flexorill is, all right? That's a muscle relaxant. Cyclo? I don't know that part. It's a cyclo, because you guys are cycling and flexing. I don't actually know. just know it's a muscle relaxant, so that's about as far as I got. When we're looking at antitick platelets, so that's the brick part, so that's going to be your, you know,   Hecagrelor, Breitlingta, Clopidogrel is the most common one. It's the cheapest one, so probably see that one the most. Those, I mean, there's an exception to every rule, but that's generally being used after like a stent's placed in the heart. It can be used for VTE, there's some out there, but that's pretty rare. But also for some valves that are placed in the hearts, it can be used for that as well. So antiplatelet, really thinking more like a cardiac event, right? Like I said, there's always an exception to every rule, but that's kind of where my mind goes real quickly, because we're gathering information from the patient.   They're on anticoagulant. Those are like going to be the new ones that you see commercials for all the time. So Xeralto, Alequis, those are the two big ones right now. They're replacing the older one. And also we were supposed to do a disclaimer of this is current as of today because the ADA guidelines do change. this will be current as of today. And Jason, as a pharmacist, is always looking up on that. I had no clue that you are that up to speed on dental knowledge. so just throwing it out there that if you happen to catch his podcast,   a few years back that obviously check those guidelines for sure. But the new ones are the Xarelto and Eloquist. They're replacing the older ones of warfarin. Warfarin's been around for a really long time. We've seen that one. Those are anti-coagulants. So when you're looking, when a patient says that, generally they're on that medication because they've possibly had a clot in the past or they have a heart condition called atrial fibrillation. Those are kind of the two big ones. Like I said, there's always caveats to it, but that's kind of where my mind goes real quickly. And then,   as far as getting patients cleared, the American Dental Association has really good resources on their website. You can look at those and they're always refreshing that up. They even say in their own words that there's limited data around studying patients in the dental chair and with anticoagulants or anti-platelets. It's pretty limited. There's a few studies, some from 2015, some from 2018. There's one as recent as 2021, which is nice. But really, all of those studies come together and it's really more of an expert consensus.   And with that expert consensus, they have kind of simplified things for dentistry, which is really nice. ⁓ comparing that to, we have more data for like total hip replacement, total knee replacement. We have a lot of data and we know really what we should be doing around then. But going back to dentistry, we don't have as much information, so they always say use clinical judgment, but they do give some really great expert guidance on that. So if a patient's on an anticoagulant, ⁓   they generally recommend that it doesn't need to be stopped unless there's a high bleeding risk for a patient. as a provider or as a clinician in the practice, you can be looking at high bleeding risk. Some things that make an oral procedure a little bit lower risk is one, it's in the compressible site, right? Like we can actually put pressure on that site. That's the number one way to stop bleeding is adding pressure. It's not like it's in the abdominal cavity where we can't get in and can't apply pressure. So number one, that kind of reduces the bleeding risk.   is number one. Two, we can add topical hemostatic agents. Dentists would know that better than me. There's a lot of topical ways to do that. So not only pressure, but there's those things as well. And also, but there are some procedures that are a little bit more likely to bleed. And that's where you and dentists would come in hand in What's the word in APO? Oh, the APOectomy. I got it right. Good job. like, didn't you tell me last night that the ADA guideline was like what?   three or four or more teeth? great question. So you can extract one to three teeth is what their expert consensus One to three teeth without. Without really managing or stopping anticoagulation or doing anything like that. I think that's some good guidance from them. I'm gonna add a Jasonism on that though. So with warfarin, I do see why dentists would be a little bit more conservative or worried about stopping the warfarin because warfarin isn't as stable as these newer agents. Warfarin, the levels.   quote unquote levels can go really high, they can go really low. And if the warfarin levels are high, they're more likely to bleed. So I do think it makes sense to have a really recent INR. That's how we measure what the warfarin's doing. I think that makes a lot of sense, but the ADA guidelines really go into the simplification version of all these blood thinners. Generally, it's recommended to not stop them because the risk of stopping them outweighs the benefit of stopping them in almost every case. Almost every case.   ⁓ So when you're with that patient, right, they say I'm on a blood thinner, finding out which kind of blood thinner that they're on, you find out that they're on Xeralto, right? How long have you been on Xeralto for? I've been on it for years. You don't know exactly why, but if they haven't had any recent bleeding, you're only gonna remove one tooth. ⁓ You can do what's called a HasBlood score. That kind of looks at the bleeding risk that they'd have. That'd be kind of going a notch above, but in my mind, removing one tooth isn't a real serious bleeding risk. I'd love to hear from my dentist friends if they...   disagree, right, but ADA says one to three tooth removals, extractions, that's the fancy word. Extractions, yeah, for extracting teeth out. Is not really that invasive. Sure. It's not that high risk, so it's usually perfectly fine. So if a patient was on Xarelto, ⁓ no other, this is in a vacuum, right? I'm not looking at any other factors, which you should be looking at other factors. I would be perfectly fine to just remove one to two.   And when those clearances come in, because dentists do send them, talk about what happens. You guys were working in the hospital and you guys would get these clearances all the time. do. We get them so often. I mean, we get like four or five a day. We'd love to give it to our students, student pharmacists, and ask them what to do. And they would usually look up the American Dental Association guidelines and come up with something. We're like, yep, that's what we say too. In fact, we say it so many times a day that we have a smart phrase.   which just blows in the information real quickly and faxes it right back to the So it's like a copy paste real quick. So what I wanted to point out when Jason told me this is dentists like hearing this and learning this, this can actually save you guys a ton of time to be able to be more confident, to not need to send those clearances on. And we were actually talking last night about how I think this might be a CYA for dentists. like, as we were talking, I think Jason, you seeing so many other aspects of medicine, like you've literally seen patients die, you've seen other areas.   And so coming from that clinical vantage point, we were realizing that dentists, we are so blessed to live in an injury. I enjoy dentistry because possibly there's someone dying, not super high, luckily in dentistry. The only time that I have actually had a doctor have a patient pass away, and it was only when they were completely sedated and doing ⁓ some other things, but that was under the care of an anesthesiologist. And so that's really our high, high risk. And so hearing this, Jason,   That was one of the reasons I wanted him to come on is to give you doctors more confidence of do we have to always send to a pharmacist? I mean, hearing that on the pharmacy side, they're just sending these back and not to say to not see why a to not cover this because you might be questioning like, well, do I really need to? But you also were talking about some other ways of so number one, you guys are just going to copy back the 88 guidelines. So so 88 guidelines. Yeah. And I think that that gives a lot of confidence to a provider or a dentist is that you can go to the 88 guidelines and read them, right? Like you're listening to some   nasally monotone pharmacist on a podcast. Rumor has it, people love him at the hospital. were like, you're the voice, he's been told he has a good radio So for the clinic, I was the voice. Like, yeah, you've reached the vascular clinic, right? And they're like, oh my gosh, you're the voice. But sorry, you me distracted. That'll be your next career, Jace. You're going to be a radio host. OK. I would love that. I love music. But you're hearing from a nasally guy, but you can actually read the ADA guidelines. You just go right to the ADA, click on Resources, and under Resources, it has the   around anticoagulants, I think that's the best way to get a lot of confidence about it because they have dentists who are the experts making calls on these. I'm just reiterating what they say, but I think it makes a lot of sense to help providers. And the reason why my heart goes out to you as well is having the providers that used to work underneath me, they're always looking for our views, which is a fancy way of making sure that they're drilling and filling. Can I say that? Yeah, can say drilling and filling. They're being productive, right? They're being productive, right?   They're always looking to make sure if a patient's canceling, like get somebody in here. Like I need to be helping people all day long. That's how I, we keep the lights on. That's how I help as many people. And so if you have a patient coming in the chair and it has an issue, they say I'm on Xeralto. Well, you can ask real quickly, why are you on Xeralto? I had a clot 10 years ago. my gosh. Well, yeah, we're pretty good to go. Then I'm not worried. We're only removing one tooth or we're just doing a cavity or a cleaning. Something like that. Shouldn't be an issue whatsoever because there's experts in the dental. ⁓   in the dental society, the ADA guidelines that recommend three teeth or less, minimally invasive. They really recommend if it's gonna be really high bleeding risk. And clinically, that's where you would come in, ⁓ or yourself. know, apioectomy is one that's like on the fence line. I don't know where implants set. though, and like we were talking, implants aren't usually like a date of procedure. Most people aren't popping in, having tooth pain, and we're like, let's do an implant. Now sometimes that can be the case, but typically that one's gonna have   a few other pieces involved. And so that is where you can get a clearance if you want to. ⁓ But we were really looking at this of like so many dentists that I know that you've seen will just send in these clearances because they are. And I think maybe a way to help dentists have more confidence is because you know, I love routines. I love to not have to remember things. So why don't we throw it in, have the team member set it up where every quarter we just double check the ADA guidelines. Are there any updates? Are there any other things that we need to do on that? That way you can just see like   getting into the language of this, of what do I need to do? Because honestly, you guys, know pharmacy was not a big portion for it, so, recommending different parts, but I think this is such a space where you can have confidence, and there's a few other things I wanna get to, and I you- I some pearls too. Okay, go. I'm so when she get me into talking about drugs, I'm not gonna stop. So, some other things around that too is these newer blood thinners like Xarelto Eloquist, they now have reversal agents, so a lot of providers in the past were really worried about bleeding because we can't turn it off. We can turn those off. Warfarin has reversal as well, right?   So I'm looking at these patients. It's really low risk. It's in the mouth, generally speaking. Very rarely are they a high bleeding risk. Now if you're doing maxillofacial surgery, this does not apply, right? This does not apply whatsoever. you're like general dentist, you're pediatric dentist. Yeah, yeah, and it's kind of on the fly. So just trying to really help you to be able to take care of those patients on the moment, have that confidence, look at the ADA guidelines, have that in front of you. I don't think it's a bad thing to ever...   check with their provider if you need to. If you're thinking, I feel like I should just check with the provider, I would never take that away from you. But I just want to kind of steer towards those guidelines that I have to help. But what did you want to share? No, yeah, I love that. And I think there were just a few other nuggets that we were chatting about last night that can help dentists just kind of get things passed a little bit easier. So you were mentioning that if they were named to their cardiologist, what was it? was like, who is the last? Great question. Yeah, when a patient's on a blood thinner,   It could be prescribed by the cardiologist. It could be prescribed by the family provider or could have been punted to like a vascular clinic like where I was working. It can go to any of those. And when you send that fax, right, if it goes to the cardiologist and it's supposed to go to the family care provider, like it just kind of goes, goes nowhere, right, from there. So I think it's a really good idea to find out who prescribed it last. If the patient doesn't know who prescribed their blood thinner last, you can call their pharmacy. I call pharmacies all day long.   I have noticed in the last year, they are way easier to get a hold of, which has made my job a lot easier, working on the insurance portion. So reaching out to the pharmacy, finding out who that provider is and sending it to them, because they should be able to help with that. I thought that was a good shift in verbiage that you had of asking instead of like the cardiologist, because that's who you would assume was the one. But you said like so many times you guys would take care of them, and then they go back to family practitioner, and you guys would get the clearances, but you couldn't clear because you weren't overseeing. So just asking the patient.   who prescribed their medication for them last time. That way you can send the clearance to the correct provider. then- And they might not know. You know patients, right? They're like, I don't know, my mom's or else, I don't know who gave it to me. Somebody told me I need to be on this. But at least that could be another quick thing. And then also we were talking last night about-   ⁓ What are some other things that dentists can do when like writing scripts to help them get what I think like overarching theme of everything we discussed is one how to help dentists have less I think drag through pharmacy. ⁓ Because pharmacy can take a little while and so perfect we now know the difference between anti-quag and anti-platelet. We know which medications are probably safe. We know we can check the ADA guidelines so that we were not having to do as many clearances. We also know if they're on a medication to find out and we do need a clearance.   who we can go to for the fastest, easiest result. And now, in talking about prescriptions, you had some really interesting tips that you could share with them. Yeah, so with writing prescriptions, right, pharmacies are pharmacies. So I'm not gonna say good thing or bad thing. There are challenges working with pharmacies. I'm not gonna play that down at all. ⁓ If you're writing prescriptions and having issues and kickbacks from pharmacies, there's some interesting laws around ⁓ writing prescriptions. Say that you're trying to ⁓ prescribe   augmentin, you know, 875 BID, and you tell the patient, hey, I want you to take this twice a day for seven days, and then you put quantity of seven, because you're moving fast, right? You want it for seven days, quantity of seven. Quantity would actually be 14, right? It's not that big of a deal. Anybody with common sense would say if you're taking a pill for twice a day for seven days, you need 14 tablets. But LAHA doesn't allow pharmacists to make that kind of a change, unfortunately. They have to follow what you're saying there. So you're going to get a...   An annoying callback that says, you wrote for seven tablets. I know you need 14. Is that OK? Just delays things, right? So ⁓ I really like the two letters QS. That's Q isn't queen. S isn't Sam. Yeah. It stands for quantity sufficient. So you don't have to calculate the amount of any medication that you're doing. So for me, as a pharmacist, when I was taking care of patients, I hated calculating the amount of insulin they would need for an entire month. So I would say.   Mrs. Jones needs 15, I'd say 15 units ⁓ QD daily. ⁓ And then I say QS, quantity sufficient, ⁓ 90 day supply through refills. So the pharmacy can then go calculate how much insulin that they need. I don't have to even do that. So anytime you're prescribing anything, I like that QS personally. So that lets the pharmacy use ⁓ common sense, as I like to call it, instead of giving you a call. I think that's super helpful. I also thought of one thing too.   going back to blood thinners is when it's kind of like a real quick, like they're not gonna have you stop the blood thinner at all. like you're seeing if you can stop the blood thinner for a patient, there's some instances it's just not gonna happen. And that's whenever they've been, they've had a clot or a stroke or a heart attack within the last three months. Three months. Yeah, that's kind of like the.   Because so many people are like, they had a heart thing like six years ago. And so I think a lot of my dentists that I worked with were like, we got to stop the blood thinners. But it sounds like it's within three months. Yeah, well, I'm just the time. Like this is general broad strokes. What I'm just trying to say is when you want to expect a no real quick. Got it. Right. So because benefits of stopping a blood thinner within those first three months of an event is very, very risky versus the, you know, the benefit of reducing a little bit of blood coming out of the mouth. Right. Like that's not that bad.   when somebody's had a stroke or a heart attack or pulmonary embolism, a clot in the lung, like we can't replace the lung, heart or brain very easily. We can replace blood a lot better. We've got buckets of it at most hospitals have buckets of it, right? So I'm always kind of leaning towards I'd rather replace blood than tissue at all times. So that's kind of a quick no. If they've had one those events in the last three months, we are really, really gonna watch their brain instead of getting.   root canal, right? Like really worried about them. So you'll just say no. And they could the dentist still proceed with the procedure or would you recommend like a three month wait? Or is it provider specific way the pros and cons because sometimes you need to get that tooth out. Great question. think then it's going to come into clinical. That's that's when you send in the clearance, right? Like, and it's great to reach out to the provider who's managing it for you. But I think it's kind of good to know exactly when you get a quick no quick no is going to be less than three months.   ⁓ Or when it's going to be like a kind of a typical, yeah, no problem. If it's been no greater than six months, they're on the typical anticoagulants or alto eloquence. Nothing crazy is going on for them. You're only removing two teeth. This is very, very low risk. But again, I'd urge everybody to read the ADA guidelines. That way you feel more comfortable with it. I'm not as eloquent as they do. They do a real good job. So I don't want to take any of their credit. I think they do a real good job of simplifying that and making you feel confident with providing.   more timely care for patients. Which is amazing. And Jayce, one last thing. I don't remember what it was. You were talking about the DEA and like six month rule. yeah. Let's just quickly talk about that and then we'll wrap this because this is such a fascinating thing for me last night. Yeah. So when comes to prescribing controlled substances, most providers have to have a DEA license. OK. First of all, though, what's your take on dentist prescribing controlled substances? ⁓ I don't think, you know, I worked on the insurance side of things. Right. And I look at the requirements for the   as the authorizations, what a patient, the criteria a patient needs to hit in order to qualify for certain medications. A lot of times for those controlled substances, they have pretty significant issues going on, like fibromyalgia or cancer-related pain or end-of-life care versus we don't, in all my scanning thread, I don't have a ⁓ perfect picture memory. Sure. But I don't usually see oral.   pain in there. There is some post-operative pain that can be covered for those kind of medications but I really recommend to keep those lower and in fact in a lot of our criteria it recommends you know have they tried Tylenol first, they tried, have they filled NSAIDs or are they contraindicated with the patient. So really they should be last line for patients in my two cents but there's always going to be a caveat to the rule right? Of course. comes through that has oral cancer and you're taking   like that would make sense to me. Got it, so then back to the DEA. Yeah, okay. Okay, ready. So as a provider, you should be checking the, if you're doing controlled substances, you should be checking the prescription drug monitoring program, or sometimes called the PDMP, looking to see if patients are getting ⁓ controlled substances from another provider. So it's really just a check and balance to make sure that they're not going from provider to provider to getting too many narcotics and causing self harm or harm to others.   And so with checking that PDMP before prescribing, I think a lot of providers do that. A lot of softwares that I'm aware of, EMRs, electronic medical records, sometimes have links so that you can do that more quickly. However, I don't think it's as intuitive that they need to be checking that every six months in some states. And like here in Nevada, you're supposed to be checking it every six months, not for a patient, but for your actual DEA registration to see if anybody else is prescribing underneath you. Because if you don't check that every six months, you could get in some serious trouble with...   not only DEA, but even more the Board of Pharmacy and your state. Now, I don't know all 50 states, so I check with your state to see if you need to be checking that every six months, but set an alarm just to check that real quickly, keep your nose clean. ⁓ I've had providers, I've had to remind to do that. And if somebody was using your account, prescribing narcotics, you'd never know unless you went and checked that PDMP.   Yeah, I remember last night you were like, and if that was you, I would not want to be you. The Board of Pharmacy is going to be real excited to find you. So that was something where I was like, got it. So, and we all know I'm big on let's make it easy. And Jason, I love that you love this so much and you just brought so much value today. And like also for me, it's just fun to podcast. fun. Yeah. But I got a nerd out on my world a little bit. Bring it into yours. I work with dentists or at least you know, when I was working in Vascular Clinic all day long. Great questions that would come through. Yeah.   So I think for all of us, as a recap on this is number one, I think setting yourself ⁓ some cadences. So maybe every quarter we check our ADA guidelines and we check our, what is it, PDMP. PDMP. so each state, so they call it Prescription Drug Monitoring Program. We need that. Yeah, but there are different acronyms in different states, though. That's just what it's called in Nevada. I forget what it is in California, but you can check your state's prescription monitoring program, make sure that opioids aren't being prescribed under your name. Got it. So we just set that as a cadence.   We know one to three teeth most likely if they're on a blood thinner is According to the 88 as of today is good to go You know things that are going to get a quick know are going to be within the last three months of the stroke the heart attack or the Clot I'm thinking like the pulmonary embolus. Yeah, that's what we're trying to prevent   Those are gonna be quick knows and then if we're prescribing, let's do QS. We've got quantity is sufficient so that we're not getting phone calls back on those medications that we are. And then on narcotics, just being a bit more cautious. Of course, this is provider specific and in no way, or form did Jason come on here to tell you you are the clinical expert.   Jason's the clinical expert on medications. And if you guys ever have questions, I know Jason, you geek out and you want to talk to people so that anyone wants to chat shop. Be sure to reach out and we'll be able to connect you in. we've even talked about possibly, so let me know listeners. You can email in Hello@TheDentalATeam.com of ask a pharmacist anything. I talked to Jason. I was like,   We'll just have them like send in questions and maybe get you back on the podcast or we do a webinar. But any last thoughts, Jace, you've got of pharmacy and dentistry as we as we wrap up today? No, I think that's pretty much it. So check the ADA guidelines. I think it's really good to have cross communication between professions. Right. If you're working with the pharmacy, CVS, Walgreens or something like that or Walmart, I know that it can be challenging. Right. They're under different pressures. You're under different pressure. So I think ⁓ just coming in with an understanding, not being angry at each other.   you know what mean, is super beneficial and working together. When it comes to it, every dentist that I've talked to is actually worried about their patient. Every pharmacist that I've worked with is really worried about the patient as well. So we're trying to accomplish the same thing, but we have different rules and our hands are bound in different ways that annoy each other, right? Like I know Dr. Jones, want 14 tablets, but you said seven. And I know Common Sense says I should give them 14, but I've got to make that change.   knowing that their hands are tied by the law. They can't use as much common sense, which is aggravating. I mean, that's why I love what I gotta do here. I gotta just kind of help a lot more and use common sense and improve patient care. But those kinds of things I think are really beneficial as you work together and then not being so afraid of blood thinners, right? So I think those guidelines do a great job of giving you confidence and not worrying about the side effects. And there's a lot of things that you can do locally for bleeding.   You have a lot of control over that. I think that's pretty cool, the tools they have. Yeah. And at the end of the day, yes, you are the clinician. You are the one who is responsible for this. so obviously, chat, but I think collaborating, talking to other pharmacists, talking to them in your state, finding out what are the state laws, things like that I think can be really beneficial just to give you peace of mind and confidence. And again, dentistry, are maybe a bit more risk adverse because luckily we don't have patients dying That's great thing. Yeah, that's fantastic. I want my dentists to be risk adverse. I think so too. But Jason, I appreciate you being on the podcast today.   And for all of you listening, ⁓ more confidence, more clarity, more streamline to be able to serve and help our patients better. if we can help you in any way or you've got more questions, reach out Hello@TheDentalATeam.com. And as always, thanks for listening. I'll catch you next time on the Dental A Team podcast.  

Commentary by Dr.  Jian'an Wang.

Commentary by Dr. Joon Ho Ahn.

Ticagrelor, a blockbuster anticlotting drug, was approved despite FDA scientists warning it looked less safe and effective than older, cheaper alternatives like clopidogrel The landmark PLATO trial used to secure approval showed U.S. patients had worse outcomes on ticagrelor, yet those results were overridden by FDA leadership Investigations revealed serious problems with the trial, including altered death records, missing data, and inconsistent monitoring that favored ticagrelor Follow-up platelet studies were also misreported, with non-significant results published as significant and some listed authors denying participation Knowing these flaws allows you to ask about proven alternatives, reduce your personal heart risk through lifestyle, and avoid dependence on drugs pushed forward with weak, flawed evidence

This week on The Beat, CTSNet Editor-in-Chief Joel Dunning speaks with Dr. Anders Jeppsson, a cardiothoracic surgeon at Sahlgrenska University Hospital in Gothenburg, Sweden, about his paper on “Ticagrelor and Aspirin or Aspirin Alone After Coronary Surgery for Acute Coronary Syndrome,” published in The New England Journal of Medicine. Chapters 00:00 Intro  01:54 Ghana Mission Trip  06:23 JANS 1, Pig-to-Human Transplant  08:08 JANS 2, CABG Acute Type A AD  10:06 JANS 3, Chylothorax Lymph Node Management  11:22 JANS 4, ICU Resternotomy Adoption  13:38 JANS 5, Octogenarians Repair vs MV Surgery  15:10 Career Center  15:31 Video 1, MVR Patent Bilateral IMammary Grafts  16:36 Video 2, Repeat RA Thoracotomy  17:39 Video 3, Vascular Injuries in Robotics  19:12 Dr. Jeppsson Interview  33:30 EACTS 2025 & Upcoming Events  They began by providing an overview of the study, including the reason for conducting it, the expansion of the study to other Nordic countries, and its results. They also discuss the funding for the research and the recruitment process. Additionally, they cover dual antiplatelet therapy and compare this study with similar research. Finally, they explore registry-based studies and future research on ticagrelor and aspirin, or aspirin alone, following coronary surgery for acute coronary syndrome.  Joel also highlights recent JANS articles exploring whether protective coronary artery bypass grafting improves surgical outcomes in acute type A aortic dissection with coronary ostial involvement, the association of chylothorax with aggressiveness of lymph node management during pulmonary resection, if intensive care unit resternotomy should be practiced in all facilities that perform cardiac surgery, transcatheter edge-to-edge repair vs mitral valve surgery in octogenarians, and research using pig-to-human lung xenotransplantation into a brain-dead recipient.  In addition, Joel explores robotic mitral valve replacement in a patient with patent bilateral internal mammary grafts, repeat right axillary thoracotomy as a safe and feasible approach for repair of recurrent LAVVR after previous AVSD repair, and handling vascular injuries in robotic thoracic surgery. Before closing, Joel highlights upcoming events in CT surgery.    JANS Items Mentioned  1.) Protective Coronary Artery Bypass Grafting Improves Surgical Outcomes in Acute Type A Aortic Dissection With Coronary Ostial Involvement  2.) The Association of Chylothorax With Aggressiveness of Lymph Node Management During Pulmonary Resection  3.) Expert Opinion: Intensive Care Unit Resternotomy Should Be Practiced in All Facilities That Perform Cardiac Surgery  4.) Transcatheter Edge-to-Edge Repair Versus Mitral Valve Surgery in Octogenarians: Comparative Analysis of Safety, Durability, and Survival  5.) Pig-to-Human Lung Xenotransplantation Into a Brain-Dead Recipient  CTSNet Content Mentioned  1.) Robotic Mitral Valve Replacement in a Patient With Patent Bilateral Internal Mammary Grafts: A Case Video  2.) Repeat Right Axillary Thoracotomy Is a Safe and Feasible Approach for Repair of Recurrent LAVVR After Previous AVSD Repair   3.) Handling Vascular Injuries in Robotic Thoracic Surgery: Real-Life Cases Using a Fibrin-Based Hemostatic Technique  Other Items Mentioned  1.) Ticagrelor and Aspirin or Aspirin Alone After Coronary Surgery for Acute Coronary Syndrome   2.) Perfecting TAVR Removal | Skills Sharpening With Vince Gaudiani  3.) Career Center   4.) CTSNet Events Calendar  Disclaimer The information and views presented on CTSNet.org represent the views of the authors and contributors of the material and not of CTSNet. Please review our full disclaimer page here.

This week on The Beat, CTSNet Editor-in-Chief Joel Dunning speaks with Adanna Akujuo, a cardiothoracic surgeon and the surgical director of the Structural Heart Program at UVA Health University Medical Center, about the Voom Foundation and its trips to Africa. Chapters 00:00 Intro 01:39 Dr. Akujuo, Medical Missions 21:57 JANS 1, Ticagrelor and Aspirin Coronary 25:20 JANS 2, Long-Term MVR Durability Model 27:37 JANS 3, Duration of Donor Ventilation 29:18 JANS 4, Min Inv Concomitant Tri VR 31:40 JANS 5, Soft Robotic Artificial Hybrid Heart 33:32 Career Center 34:20 Video 1, RVOT Injury During Dissection 37:05 Video 2, Min Inv ASD Closure 38:31 Video 3, Redo AVR via Partial U Resternotomy 40:08 Upcoming Events 40:54 Closing They explore the foundation's goals, including training and educating local medical staff and providing essential care. Additionally, Dr. Akujo offers insights into the upcoming trip, discussing what a typical day entails, transportation logistics, accommodation, and the expenses that surgeons participating in the trip will need to cover, as well as what costs are taken care of by the foundation. The conversation also covers security measures in place, the average number of staff members on these trips, the daily surgical volume, and the most common cases.   Joel also highlights recent JANS articles on which is best, ticagrelor and aspirin or aspirin alone after coronary surgery for acute coronary syndrome; an artificial intelligence and machine learning model for personalized prediction of long-term mitral valve repair durability; effect of duration of donor ventilation on lung transplant outcomes; surgical decision-making for concomitant tricuspid valve repair in minimally invasive mitral valve surgery; and a soft robotic total artificial hybrid heart.  In addition, Joel explores right ventricular outflow tract injury during deep dissection in valve-sparing aortic root replacement, a minimally invasive approach for atrial septal defect closure, and redo aortic valve replacement via partial upper resternotomy. Before closing, Joel highlights upcoming events in CT surgery.    JANS Items Mentioned  1.) Ticagrelor and Aspirin or Aspirin Alone After Coronary Surgery for Acute Coronary Syndrome  2.) An Artificial Intelligence and Machine Learning Model for Personalized Prediction of Long-Term Mitral Valve Repair Durability  3.) Effect of Duration of Donor Ventilation on Lung Transplant Outcomes  4.) Surgical Decision-Making for Concomitant Tricuspid Valve Repair in Minimally Invasive Mitral Valve Surgery  5.) A Soft Robotic Total Artificial Hybrid Heart  CTSNET Content Mentioned  1.) Right Ventricular Outflow Tract Injury During Deep Dissection in Valve-Sparing Aortic Root Replacement   2.) Minimally Invasive Approach for Atrial Septal Defect Closure  3.) Redo Aortic Valve Replacement Via Partial Upper Resternotomy  Other Items Mentioned  1.) Voom Foundation   2.) Career Center   3.) CTSNet Events Calendar  Disclaimer The information and views presented on CTSNet.org represent the views of the authors and contributors of the material and not of CTSNet. Please review our full disclaimer page here.

Approval of first-generation devices, the ticagrelor controversy, ICD longevity, the PRAGUE-25 trial (one of the most important trials of the year), and some thoughts on the end of EP as a profession are the topics John Mandrola, MD, discusses in this week's podcast. This podcast is intended for healthcare professionals only. To read a partial transcript or to comment, visit: https://www.medscape.com/twic I More Ticagrelor Controversy BMJ Investigation Finds More Concerns in Ticagrelor Trials https://www.medscape.com/viewarticle/investigation-bmj-raises-more-concerns-about-ticagrelor-2025a1000gh3 Ticagrelor PLATO study https://www.bmj.com/content/389/bmj.r1201 Ticagrelor vs Clopidogrel https://www.nejm.org/doi/full/10.1056/NEJMoa0904327 Review of the Ticagrelor Trials Evidence Base https://www.ahajournals.org/doi/10.1161/JAHA.123.031606 The Plato Trial: Do you believe in magic? https://doi.org/10.1093/eurheartj/ehp545 ONSET/OFFSET Antiplatelet Effects https://www.ahajournals.org/doi/10.1161/circulationaha.109.912550 RESPOND Study https://www.ahajournals.org/doi/10.1161/circulationaha.109.919456 II ICD Battery Longevity Variability in ICD Battery Longevity https://doi.org/10.1016/j.hrthm.2025.05.031 PRAGUE-25 Trial of AF Ablation vs LFM PRAGUE-25 Trial https://www.jacc.org/doi/10.1016/j.jacc.2025.04.042 You may also like: The Bob Harrington Show with the Stephen and Suzanne Weiss Dean of Weill Cornell Medicine, Robert A. Harrington, MD. https://www.medscape.com/author/bob-harrington Questions or feedback, please contact news@medscape.net

FACT (fentanyl And Crushed Ticagrelor) PCI: A Randomized Control Trial of Patients Undergoing Percutaneous Coronary Intervention Who Receive Ticagrelor and Fentanyl

Witam Państwa, nazywam się Jarosław Drożdż, pracuję w Centralnym Szpitalu Klinicznym Uniwersytetu Medycznego w Łodzi, skąd nagrywam podcast Kardio Know-How. W tym odcinku omawiam różne metody leczenia p/płytkowego po OZW. 5 Strategii Leczenia Rok po Zawale Serca1. Klasyczna – Rytm zatokowyStandardowa terapia przeciwzakrzepowa i antyagregacyjna przy utrzymanym rytmie serca.2. Klasyczna – Migotanie przedsionkówLeczenie oparte na doustnych antykoagulantach (głównie DOAC), dostosowane do współistniejącego AF.3. Nowoczesna – Udar / Choroba tętnic obwodowych (PAD)Zwiększona intensywność terapii przeciwzakrzepowej (np. dualna strategia DOAC + P2Y12) w grupie wysokiego ryzyka powikłań niedokrwiennych.4. Nowoczesna – Duże ryzyko niedokrwienneRozszerzona terapia przeciwpłytkowa, ukierunkowana na precyzyjne obniżenie ryzyka nawrotu zawału.5. Bardzo nowoczesna – Alternatywa dla klasycznej terapiiNowe podejścia: np. monoterapia inhibitorem P2Y12 (Ticagrelor) zamiast klasycznego ASA, szczególnie tam, gdzie kluczowe jest ograniczenie krwawień.

Last December, The BMJ published an investigation into the 2009 PLATO trial - exposing serious problems with that study's data analysis and reporting.  Our follow up investigation has shown that those data problems extend to other key supporting evidence in AstraZeneca's initial application to regulators. Peter Doshi, senior editor in the BMJ's Investigations unit, and Rita Redberg, cardiologist and Professor of Medicine at UCSF and former editor of JAMA Internal Medicine, join us to explain what this means for scientific integrity, and trust in the FDA's approval processes.   Also in this episode. A group of international authors are arguing that weightloss advice given in primary care might actually be doing more harm than good - it's ineffective and potentially reinforces damaging stigma.  To explain why they came to that conclusion we're joined by Juan Franco editor in chief of BMJ EBM, and a practicing GP in Germany, and Emma Grundtvig Gram, from the Centre for General Practice at the University of Copenhagen Reading list Doubts over landmark heart drug trial: ticagrelor PLATO study Ticagrelor doubts: inaccuracies uncovered in key studies for AstraZeneca's billion dollar drug Beyond body mass index: rethinking doctors' advice for weight loss

In this episode of the Scope of Things, host Deborah Borfitz delivers the news on an investigation into data reporting problems in major Ticagrelor clinical trial PLATO, the need for more sex-aware cancer research, Alzheimer's studies looking at brain shrinkage associated with immunotherapies (and repurposing drugs as potential new treatments), and a large, decentralized trial that successfully uncovered disease-causing genetic variants in hundreds of participants. Benjamin Vandendriessche, chief delivery officer of Digital Medicine Society, also joins in to talk about a newly completed project with the FDA that is providing guidance and resources on how to validate novel digital clinical measures.  News Roundup PLATO trial investigation Findings published in The BMJ “OncoSexome” project Paper in Nucleic Acids Research Brain shrinkage with Alzheimer's treatment Research in The Lancet Neurology  Repurposing drugs for Alzheimer's Study in Alzheimer's & Dementia  Mayo Clinic Tapestry study Article in Mayo Clinic Proceedings Guest  Benjamin Vandendriessche, chief delivery officer, Digital Medicine Society The Scope of Things podcast explores clinical research and its possibilities, promise, and pitfalls. Clinical Research News senior writer, Deborah Borfitz, welcomes guests who are visionaries closest to the topics, but who can still see past their piece of the puzzle. Focusing on game-changing trends and out-of-the-box operational approaches in the clinical research field, the Scope of Things podcast is your no-nonsense, insider's look at clinical research today.

Our initial review of the PLATO trial, published in April 2024, was based on the data available to us at that time. We have since became aware of new information that reduces our confidence in the PLATO results. This new information has major implications for clinical practice. Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.Despite representing only 6.9% of the total P2Y12 inhibitor prescriptions among Medicare beneficiaries in 2020, Ticagrelor accounted for nearly two-thirds of total Medicare spending on these drugs in the same year. We summarize important points below but you can refer to this investigation at BMJ for more details.1. Unexplained Regional Variation: In our original review, we highlighted the treatment effect interaction based on region of enrollment, where ticagrelor was less effective compared to clopidogrel for patients enrolled in North America. It appeared to be a strong signal and was associated with a p-value for the interaction of 0.05. However, we were cautious in our interpretation since overall, patients enrolled in North America represented a relatively small fraction of total patients and we could not think of a reasonable explanation.Information in the BMJ investigation now sheds new light on these findings. In our review, we only presented data contained in the supplement accompanying the PLATO trial manuscript, which categorized patients based on region of enrollment but did not provide country specific information. The BMJ report notes that in a separate subgroup analysis, based on country of randomization, the primary outcome was numerically higher with ticagrelor in the United States (12.6% vs 10.1%, HR: 1.27, 95% CI: 0.92 – 1.75). This subgroup represented 7.6% of the total trial participants. Overall, 9.7% of trial participants were enrolled from North America. This means the US data drove the findings from the North American subgroup.The explanation provided by AstraZeneca (the manufacturer of ticagrelor) to explain the observed treatment effect heterogeneity was that aspirin dosing in the United States was higher than in other countries. It even led the FDA to issue a black box warning to avoid an aspirin maintenance dose of >100 mg in patients taking ticagrelor. An extensive statistical analysis of the regional variation in PLATO yielded four interesting points. First what was the prior likelihood of observing a ticagrelor vs clopidogrel HR of > 1.25 in the US, when the overall HR was actually equal to 0.84? That probability is ≤ 0.01. This alone suggests more than chance. Second point: a strong US/nonUS interaction was noted for each of the 3 components of the primary endpoint—CV death, MI, stroke. Third: they found a very strong interaction between treatment and median aspirin dose, and, importantly, the aspirin interaction effect was similar in US and nonUS settings. Fourth, an analysis of contract research organization (CRO) vs sponsor monitoring of the site accounted for 61% of the treatment-by- region interaction. The authors downplayed this finding because of the four countries monitored by a CRO (Israel, US, Georgia and Russia), the US made up the majority and thus is confounded by the aspirin interaction. Noteworthy was a lack of direct analysis of CRO vs sponsor test for interaction. One problem though: the BMJ investigation found that the lead author, Kevin Carroll was the head statistician at AstraZeneca and had worked at the company for 20 years. Carroll presented the PLATO results at the FDA advisory meeting. The paper lists Carroll as having no conflicts. Carroll told the BMJ that he had disposed of all conflicts of interest before submitting that analysis. But, in our opinion, the aspirin explanation does not pass muster because of biologic implausibility. See next section: How would a higher dose of aspirin reduce the efficacy of ticagrelor?The primary composite endpoint was vascular death, MI or stroke. If the higher aspirin dose impacted this, we would hypothesize that it caused more major bleeding in the ticagrelor group with some events resulting in vascular death, type 2 MI and hemorrhagic stroke, driving the treatment effect in favor of clopidogrel. But there is no evidence of this.The figure below is from the original subgroup plots provided in the PLATO supplement. The difference in the treatment effect for the primary endpoint for North American patients is striking but there is no difference for major bleeding.In our opinion and the opinion of others, the role of supervision of the centers could be important. Most centers were monitored by the sponsor. Four countries (Israel, US, Georgia and Russia) were monitored by a contract research organization. All four of these countries had numerically higher rates of the primary outcome in the ticagrelor group. This has major implications and we do not take them lightly. Essentially, it suggests malfeasance on the part of the sponsor. So is there anything else to support such a claim? Well, yes. 2. Concerns about event adjudication. Based on a report from Victor Serebruany, an adjunct faculty member at Johns Hopkins University, and the BMJ investigation, FDA records indicated that site reports documented 504 myocardial infarctions in patients who received ticagrelor compared to 548 in patients who received clopidogrel. However, after adjudication, the count increased only for the clopidogrel group, reaching 593. There was also some imbalance among groups in adjudicating death. These imbalances raise concerns about potential unblinding and result tampering. We read many of the authors' replies and we did not find a clear explanation of why all readjudicated extra MIs were in the clopidogrel group (45 clopidogrel; ticagrelor 0). 3. There were also concerns about the accuracy of death records as sites death records did not always match the FDA records.We cite from the BMJ: The BMJ's analysis also found omissions in PLATO's landmark publication. The paper, published in NEJM and reported as an intent-to-treat analysis, reports 905 total deaths from any cause among all randomized patients. An internal company report states, however, that 983 patients had died at this point. While 33 deaths occurred after the follow-up period, the NEJM tally still leaves out 45 deaths “discovered after withdrawal of consent.” The BMJ obtained some records for patients whose deaths were not reported in NEJM (see table 1) and asked the journal for a response.NEJM editor in chief Eric Rubin told The BMJ that “for older manuscripts, correction is not necessarily appropriate unless there would be an effect on clinical practice,” concluding that “it does not appear that correcting this 15-year-old article is going to have any impact.”It is noteworthy that the United States Department of Justice launched a formal investigation into the PLATO trial in 2013; however, the probe was closed in 2014. The BMJ column cited a spokesperson for the US attorney's office who said…”we determined that the allegations lacked sufficient merit such that it was not in the best interests of the US to intervene in the suit.” 4. Mortality reduction in PLATO defies explanation: Shortly after PLATO was published, Drs. Victor Serebruany and Dan Atar wrote an editorial in the European Heart Journal titled: The PLATO trial: do you believe in magic? They noted that the overall HR for all-cause death ticagrelor vs clopidogrel was 0.78 (95% CI: 0.69 - 0.89; p< 0.001). There were 107 more lives saved with ticagrelor vs clopidogrel. To explain the surprise of this massive effect size, they compared it to the COMMIT trial of clopidogrel vs placebo in patients with acute MI. In COMMIT, 119 lives were saved with clopidogrel (vs placebo), but COMMIT had three-fold more patients than PLATO—and the gain was vs placebo. They tempt the reader to ask: how could ticagrelor fare that well against a drug that crushed placebo? We note two other reasons to be concerned about the outsized mortality reduction in PLATO. One is plausibility. The all-cause mortality benefit exceeded the reduction in MI, CV death or stroke. Given the numerically higher rate of bleeding, how else does ticagrelor reduce death vs clopidogrel? The second reason is the lack of such a signal in Phase 2 studies, such as this one. 5. PLATO results are on outlier: Multiple observational studies have failed to replicate the benefits of ticagrelor observed in the PLATO trial. While observational studies are inherently limited by confounding factors and are inferior to randomized trials, their findings warrant a re-evaluation of ticagrelor's benefits. Furthermore, two randomized trials—one conducted predominantly in Japanese patients and another in South Korea—did not demonstrate the superiority of ticagrelor, instead showing higher bleeding rates and a numerical increase in ischemic events.Ticagrelor also significantly underperformed against another new antiplatelet drug, prasugrel. In the non-industry-funded ISAR-REACT 5 trial, which enrolled patients with acute coronary syndrome, the primary event of death, MI, or stroke was 36% higher in the ticagrelor arm (9.3% vs 6.9%, HR 1.36, 95% CI: 1.09 - 1.70). Major bleeding was also numerically higher in the ticagrelor arm. 6. PLATO authors have responded to these arguments.We provide links to four of the authors responses. * Thrombosis and Hemostasis https://www.wellesu.com/10.1160/TH11-03-0162* Stroke https://www.ahajournals.org/doi/10.1161/strokeaha.111.000514* Inter J of Cardiol https://doi.org/10.1016/j.ijcard.2014.06.029* Circulation https://doi.org/10.1161/CIRCULATIONAHA.111.047498Conclusion These are vitally important revelations regarding PLATO and ticagrelor. The FDA advisory committee recommended that FDA require a confirmatory trial. This was not done. As such, ticagrelor gained serious market share in the non-clopidogrel antiplatelet market for more than a decade. Yet no other compelling evidence for its benefit over clopidogrel has come to light. It clearly underperformed vs prasugrel. These old and new revelations have changed our positive view of ticagrelor. We no longer have confidence in this drug. We strongly agree with the recommendation for another properly controlled trial. We also believe this highlights the benefits of having either two regulatory trials or a single regulatory trial combined with a mandated post-approval trial. These revelations also emphasize the benefits of robust critical appraisal and skeptical but not cynical approaches to surprising evidence. Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

TWiM explains how ticagrelor alters the membrane of S. aureus and enhances the activity of vancomycin and daptomycin without eliciting cross-resistance, and the development of a novel continuous disinfectant technology that decreases healthcare-associated infections in ICUs by 70%. Hosts: Vincent Racaniello, Michael Schmidt, and Michele Swanson. Become a patron of TWiM. Links for this episode Ticagrelor and S. aureus (mBio) Novel disinfectant technology (Am J Inf Control) UVC-LED to inactivate foodborne pathogens (Appl Envir Micro) UV disinfection systems (ACS Photonics) High-touch surfaces in specialized patient care area (CDC) Take the TWiM Listener survey! Send your microbiology questions and comments (email or recorded audio) to twim@microbe.tv  

34th ESC 2024: Ticagrelor monotherapy vs. dual antiplatelet therapy

In this episode of Medmastery's Cardiology Digest, we dive into three groundbreaking studies that are set to reshape our understanding and approach to cardiology. STUDY #1: First, we discuss a landmark piece of research that sheds new light on the benefits of percutaneous coronary intervention for patients with significant coronary artery disease who need a transcatheter aortic valve replacement. This study addresses important questions about patient selection for this intervention.   Lønborg, J, Jabbari, R, Sabbah, M, et al. 2024. PCI in patients undergoing transcatheter aortic-valve implantation. N Engl J Med. Published online. (https://doi.org/10.1056/NEJMoa2401513) STUDY #2: Next, we examine an insightful meta-analysis that evaluates patient-level data to inform the future of dual antiplatelet therapy after percutaneous coronary intervention. Discover the factors influencing the transition to ticagrelor monotherapy post-PCI and why this could change current guideline recommendations.  Valgimigli, M, Hong, S, Gragnano, F, et al. 2024. De-escalation to ticagrelor monotherapy versus 12 months of dual antiplatelet therapy in patients with and without acute coronary syndromes: A systematic review and individual patient-level meta-analysis of randomized trials. Lancet. 10456: 937–948. (https://doi.org/10.1016/S0140-6736(24)01616-7) STUDY #3: Lastly, we take a closer look at the EPIC-CAD study, which aligns with previous findings from the AFIRE trial. Learn why anticoagulant monotherapy is now being considered for the majority of patients with atrial fibrillation who require anticoagulation and have stable coronary artery disease, and what this means for your clinical practice. Cho, MS, Kang, D-Y, Ahn, J-M, et al. 2024. Edoxaban antithrombotic therapy for atrial fibrillation and stable coronary artery disease. N Engl J Med. Published online. (https://doi.org/10.1056/NEJMoa2407362) Tune in to this episode for an engaging in-depth discussion of these studies and stay ahead in the ever-evolving field of cardiology!  Learn more with Medmastery's courses: Percutaneous Coronary Intervention Essentials (6 CME) Percutaneous Coronary Intervention Essentials Workshop (6 CME) Get a Basic or Pro account, or, get a Trial account. Show notes: Visit us at  https://www.medmastery.com/podcasts/cardiology-podcast.

Welcome back Rounds Table Listeners!We are back today with our Classic Rapid Fire Podcast!This week, Drs. Mike and John Fralick discuss two recent papers exploring the role of ticagrelor with aspirin versus ticagrelor alone after percutaneous coronary intervention in acute MI and the efficacy of empagliflozin after acute MI. Two papers, here we go!Ticagrelor alone versus ticagrelor plus aspirin from month 1 to month 12 after percutaneous coronary intervention in patients with acute coronary syndromes (ULTIMATE-DAPT) (0:00 – 9:22). Empagliflozin after Acute Myocardial Infarction (9:22 – 16:00).And for the Good Stuff:Impact of presentation at conference with timed release of academic publication (16:00 – 17:32).Top spot in the PWHL and attendance record at stake in latest Montreal-Toronto showdown (17:32 – 19:59).Questions? Comments? Feedback? We'd love to hear from you! @roundstable

Commentary by Dr. Valentin Fuster

Ticagrelor Monotherapy in Patients with Acute Coronary Syndrome: An Individual Patient Data Meta-Analysis of Randomized TICO and T-PASS Trials

N Engl J Med 2009;361:1045-57.Background Similar to Prasugrel, Ticagrelor is a direct-acting oral antagonist of the adenosine diphosphate receptor P2Y12. Unlike clopidogrel that requires transformation of the prodrug to the active metabolite, Ticagrelor provides faster and more consistent P2Y12 inhibition.In the TRITON-TIMI 38 trial, Prasugrel compared to clopidogrel reduced myocardial infarction in patients with ACS but was associated with more major bleeding and subgroup interactions were evident for patients who were older, had a history of stroke or risk factors for bleeding and who were generally at higher risk for recurrent events.The Study of Platelet Inhibition and Patient Outcomes (PLATO) sought to test the hypothesis that Ticagrelor is superior to clopidogrel for the prevention of vascular events and death in patients presenting with ACS.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.Patients Eligible patients were hospitalized for ACS, with or without ST-segment elevation (STE), whose onset of symptoms occurred within the previous 24 hours. For patients without STE, at least 2 of the following criteria were required: 1) ST-segment changes on ECG indicating ischemia, 2) a positive biomarker indicating myocardial necrosis, or 3) one or more risk factors including age ≥60 years, previous MI or CABG, CAD with stenosis of ≥50% in at least 2 vessels, history of ischemic stroke, TIA, carotid stenosis, cerebral revascularization, diabetes, peripheral arterial disease or CKD based on creatinine clearance

Commentary by Dr. Valentin Fuster

EpicMedia-EP.32 Ticagrelor o prasugrel frente a clopidogrel en la ICP del síndrome coronario crónico. Dr Pablo Baglioni

⁠DozeNews PRIME⁠: as melhores e mais didáticas revisões de cardiologia direto na sua caixa de entrada! Assine agora e tenha acesso à todo material já produzido! - ⁠https://dozeporoito.substack.com/

Commentary by Dr Jack Tan

Dual antiplatelet Tx. with Ticagrelor and graft failure after CABG

Quanto tempo parar o ticagrelor antes de cirurgias? by Cardiopapers

In this week's episode we'll learn more about the negative findings from the phase three trial of ticagrelor for preventing vaso-occlusive crises in children with sickle cell disease, discuss how residual cytoplasmic UBA1 contributes to the pathogenesis of VEXAS syndrome, and learn more about the impact of host T-cell immunity in the response to chemotherapy in pediatric ALL.

On this episode, I discuss ticagrelor pharmacology, adverse effects, and important drug interactions. Ticagrelor has a warning with regards to the use of aspirin. Higher doses of aspirin can impair the effectiveness of ticagrelor and I discuss this further on this episode. Bleeding is the major adverse effect from ticagrelor and naturally, hematocrit and hemoglobin are important monitoring parameters. I discuss CYP3A4 drug interactions on this episode and how it may affect ticagrelor.

Pyrlcasts, brought to you by Pyrls.com! We take a closer look at interesting and relevant clinical topics related to pharmacotherapy. Want to learn more clinical pearls? Boost your clinical confidence? Visit and sign-up for an account at pyrls.com to get over 10 high-quality charts absolutely FREE! Episode References: Levine GN, Bates ER, Bittl JA, et al. 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention, 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery, 2012 ACC/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease, 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction, 2014 AHA/ACC Guideline for the Management of Patients With Non-ST-Elevation Acute Coronary Syndromes, and 2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery [published correction appears in Circulation. 2016 Sep 6;134(10):e192-4]. Circulation. Cattaneo M, Faioni EM. Why does ticagrelor induce dyspnea?. Thromb Haemost. 2012;108(6):1031-1036. doi:10.1160/TH12-08-05472016;134(10):e123-e155. doi:10.1161/CIR.0000000000000404 Krakowiak A, Kuleta J, Plech I, et al. Ticagrelor-Related Severe Dyspnoea: Mechanisms, Characteristic Features, Differential Diagnosis and Treatment. Clin Med Insights Case Rep. 2020;13:1179547620956634. Published 2020 Oct 8. doi:10.1177/1179547620956634 Undem BJ, Kollarik M. The role of vagal afferent nerves in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2005;2(4):355-372. doi:10.1513/pats.200504-033SR PLAVIX- clopidogrel tablet, film coated. Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership. Accessed via DailyMed. Updated March 5, 2021. BRILINTA- ticagrelor tablet. AstraZeneca Pharmaceuticals LP. Accessed via DailyMed. Updated May 9, 2022. PRASUGREL tablet, film coated. Accord Healthcare Inc. Accessed via DailyMed. Updated May 21, 2021.

Dear friends, in this episode we summarized recent data on potent antiplatelet therapy. You can also download the slides via this link:http://ecardiocast.com/wp-content/uploads/2022/06/antiplatelet-therapy.pdf

Dear friends, in this episode we summarized recent data on potent antiplatelet therapy and Kimiara company provided us the data on Brelor. You can also download the slides via this link:http://ecardiocast.com/wp-content/uploads/2022/06/antiplatelet-therapy.pdf

TicaHub 2

Ticagrelor and secondary prevention in CCS

CME credits: 1.50 Valid until: 25-04-2023 Claim your CME credit at https://reachmd.com/programs/cme/bentracimab-immediately-and-significantly-reverses-the-antiplatelet-effects-of-ticagrelor-in-older-people/14057/ tbd

Managing dyspnea induced by Ticagrelor

Ticagrelor in preventing post-ACS thrombotic events

The findings of TWILIGHT Trial

The dosage and indications of Ticagrelor

FDA 批准颈动脉窦压力反射刺激疗法治疗心衰Lancet 血ACE2水平与心血管疾病及死亡的关系Science子刊 一种具有几何适应性的人工心脏瓣膜BAROSTIM NEO系统BAROSTIM NEO系统包括一个植入式脉冲发生器（IPG）、一个颈动脉窦含铅套件和一个程序。医生将BAROSTIM NEO脉冲发生器植入晚期心力衰竭患者的左或右锁骨下方，并在患者的左或右颈动脉窦处放置颈动脉窦导线，然后将脉冲发生器连接到颈动脉窦导线上。医生根据病人的个人需求制定脉冲发生器程序，然后向颈动脉的压力感受器传递电脉冲。压力反射激活（BAT）疗法的目的是激活颈动脉壁的压力感受器，刺激自主神经系统的传入和传出神经，大脑接收到神经信号作出相应反应：松弛血管、降低心率、并通过改善肾功能来减少液体储留。2019年8月，FDA批准BAROSTIM NEO系统用于药物治疗无效的、不符合心脏再同步化治疗适应症的、难治性心力衰竭患者。《BeAT-HF研究：这项研究证明了压力反射刺激疗法（BAT）对射血分数降低的心力衰竭患者的安全性和有效性》Journal of American College of Cardiology，2020年7月 (1) BeAT-HF研究是一项多中心、前瞻性、随机对照研究，纳入408名射血分数降低的心力衰竭（HFrEF）患者中，入组要求：纽约心功能分级II-III级、射血分数≤35%、药物治疗方案稳定≥4周、不符合心脏再同步化治疗的I类指征。这篇报告重点汇报了D队列中、NT-proBNP

Date: October 2nd, 2020 Guest Skeptic: Dr.Barbra Backus is an emergency physician at the Emergency Department of the Erasmus University Medical Center in Rotterdam, the Netherlands. She is the creator of the HEART Score and an enthusiastic researcher. Reference: Claiborne Johnston S et al. Ticagrelor and Aspirin or Aspirin Alone in Acute Ischemic Stroke or TIA. NEJM […]

Dr. Carolyn Lam:               Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. I'm Dr. Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore.                                                 Today's feature paper is going to cause us to rethink the way we prognosticate patients with pulmonary arterial hypertension following their initial management. Think you know the hemodynamic variables? Well, stay tuned for this discussion coming right up after these summaries:                                                 Our first original paper this week shows for the first time the predictive value of coronary artery calcification progression for coronary and cardiovascular events in a population base study. Authors Dr. Erbel and Lehmann from University Hospital Essen in Germany and their colleagues evaluated several progression algorithms between CTs performed at baseline and after a mean of five years for the risk prediction of coronary and cardiovascular events in a population base cohort of more than 3,200 participants initially free from cardiovascular disease.                                                 The authors found that coronary artery calcification progression added some predictive value to the baseline CT and risk assessment, and even when the five-year risk factors were taken into account. However, the progression yielded no additional benefit when the five-year coronary artery calcification results were taken into account instead of the baseline coronary artery calcification results.                                                 Double zero coronary artery calcification scans in a five-year interval meant an excellent prognosis, which was better than the prognosis for incident coronary artery calcification after five years. Thus, the authors concluded that sophisticated coronary artery calcification progression algorithms may be unnecessary and clinicians can instead rely on the most recent risk and coronary artery calcification assessment.                                                 The next paper demonstrates for the first time cell-specific effects of Smad3 signaling in the infarcted myocardium. Now, in the infarcted heart, Smad3 signaling is known to be activated in both cardiomyocytes and the interstitial cells. In the current paper, co-first authors, Doctors Kong and Shinde, corresponding author Dr. Frangogiannis from Albert Einstein College of Medicine in New York, and their colleagues hypothesized that cell-specific actions of Smad3 may regulate, repair, and remodeling in the infarcted myocardium.                                                 In order to dissect the cell-specific Smad3 actions in myocardial infarction, these authors generated mice with Smad3 loss specifically in activated fibroblasts or in cardiomyocytes. They found that fibroblast-specific Smad3 activation played a critical role in repair following myocardial infarction by restraining fibroblast proliferation and contributing to scar organization by stimulating integrin synthesis.                                                 On the other hand, cardiomyocyte-specific Smad3 signaling did not affect acute ischemic injury, but triggered nitrosative stress and induced matrix metalloproteinase expression in the remodeling myocardium, thereby promoting cardiomyocyte death and contributing to systolic dysfunction.                                                 In summary therefore, these authors demonstrated the cellular specificity of Smad3-dependent actions that stimulate distinct cellular responses in fibroblasts versus cardiomyocytes in the healing myocardial infarction. The implications are that nonspecific therapeutic targeting of Smad3 signaling in pathologic conditions may interfere with both detrimental and beneficial actions. On the other hand, design of interventions with specific cellular targets may be needed for the development of safe and effective therapies.                                                 Good news from the next paper! Genetically predetermined high blood pressure and its complications may be offset by healthy lifestyle. Well, at least, to some extent. First author, Dr. Pazoki, co-corresponding authors Dr. Elliott from Imperial College London and Dr. Tzoulaki from University of Ioannina in Greece aimed to investigate the extent to which lifestyle factors could offset the effect of an adverse blood pressure genetic profile as well as its effects on cardiovascular disease risk.                                                 To do this, they constructed a genetic risk score for high blood pressure using 314 published blood pressure loci in more than 277,000 individuals without previous cardiovascular disease from the UK Biobank study. They scored participants according to their lifestyle factors including body mass index, healthy diet, sedentary lifestyle, alcohol consumption, smoking, and urinary sodium excretion levels measured at recruitment. They examined the association between tertiles of genetic risk and tertiles of lifestyle score with blood pressure levels and incident cardiovascular disease.                                                 They found that adherence to a healthy lifestyle was associated with lower blood pressure regardless of the underlying blood pressure genetic risk. Furthermore, adherence to a healthy lifestyle was also associated with lower risk of myocardial infarction, stroke, and the composite cardiovascular disease at all levels of underlying blood pressure genetic risk. Healthy compared to unhealthy lifestyle showed a 30%, 31%, and 33% lower risk of cardiovascular disease respectively among participants at low, middle, and high genetic risk groups. Thus, these results strongly support population-wide efforts to lower blood pressure and subsequent cardiovascular disease risk through lifestyle modification.                                                 The final paper is an aggregate report from two large randomized trials, which demonstrate for the first time that more potent antiplatelet therapy further lowers venous thromboembolism risk relative to aspirin alone. First author Dr. Cavallari, corresponding author Dr. Bonaca, and colleagues from the TIMI Study Group in the Brigham and Women's Hospital ascertained and characterized symptomatic venous thromboembolism events in more than 47,600 patients randomized in the TRA 2°P-TIMI 50 and PEGASUS-TIMI 54 trials. They evaluated risk of symptomatic venous thromboembolism over time, independent risk factors for venous thromboembolism, and the efficacy of more intensive antiplatelet strategies at reducing venous thromboembolism risk.                                                 They found that the rate of venous thromboembolism in patients with atherosclerosis was 0.3% per year while on treatment with at least one antiplatelet agent. This risk increased independently with the number of symptomatic vascular territories. Furthermore, more intensive antiplatelet therapy with Vorapaxar and Ticagrelor in this case reduced the risk of venous thromboembolism.                                                 These data suggested a relationship between atherosclerosis burden and venous thromboembolism risk. The data also support the inclusion of venous thromboembolism as a prospective endpoint in long-term secondary prevention trials evaluating the risks versus benefits of antiplatelet therapies in patients with atherosclerosis.                                                 Well, that wraps it up for our summaries. Now for our feature discussion.                                                 For our feature discussion today, we are talking about pulmonary arterial hypertension. We've learned so much from registries about prognostication of pulmonary arterial hypertension at the time of diagnosis. But these registries have only provided limited insight into the impact of therapies on long-term outcomes and how we're supposed to use variables after initiation of therapy to determine prognosis.                                                 Well, that gap is being filled by today's paper in circulation. I'm so pleased to have the first and corresponding author with us, Dr. Jason Weatherald from University of Calgary, as well as Dr. Kelly Chin, associate editor from UT Southwestern, to discuss this very important paper.                                                 Jason, congratulations on this paper. Could you tell us a bit more about what you did and why you did it, and what's exciting about what you found? Dr. Jason Weatherald:   This is a study that started during my research fellowship last year when I was spending time in Paris with the group of Professor Olivier Sitbon and Marc Humbert. We started this study based on some other recent papers showing the importance of pulmonary arterial compliance, and some smaller studies that emphasized the importance of hemodynamic variables after treatment initiation and the prognostic importance of that. We wanted to look at the relative importance of pulmonary arterial compliance as well as the stroke volume in the cardiac index in newly diagnosed patients.                                                 We looked at a 10-year cohort from the French registry of patients who had right heart catheterizations at baseline and then after treatment initiation. We looked at prognostic variables, both at baseline and at the first follow-up after initial treatment. The interesting result is that we found that actually pulmonary arterial compliance is not the most important prognostic variable, but it seemed that the stroke volume index, which was calculated from the cardiac index and the heart rate, was the most significant independent predictor of long-term survival from the hemodynamic perspective. Dr. Carolyn Lam:               Kelly, could you help point out why this is so important in clinical practice? You see a lot of these patients. In what way did this paper make you think differently about them? Dr. Kelly Chin:                    I think there's a couple different areas that really struck me. The first one was, as you mentioned in the introduction, the importance of post treatment values versus baseline values. This is not to say that the baseline values aren't important because it does still associate with survival and it's very important when choosing therapy, but as PAH therapies have become more effective, we would hope to see that the baseline severity matters less and that, indeed, seems to be what we're seeing here. That also reinforces the importance of serial reassessment to see how your patient is doing and make further decisions for therapy.                                                 The second key finding, I think, is what Jason was just talking about with which hemodynamic measures do we really want to be keeping a close eye on? Here's where, in the stepwise analysis, they found that the right atrial pressure and then, the surprising one, the stroke volume index were the key measures that were associated.                                                 Interestingly, cardiac index fell out of that model. That isn't to say that cardiac index wasn't associated with outcome. It was a predictor in the univariate analysis. But I think when you step back and you think about the comparison between those two, if you have a patient who's maintaining their cardiac index only by becoming tachycardic, they're probably not doing nearly as well as a patient who has a normal heart rate and a normal stroke volume index.                                                 I think this really struck me as something, "Hey, when I'm in the cath lab, I probably need to be thinking about this and reporting it out, so everybody's seeing it right there on the report", which is not something we've been doing. Dr. Carolyn Lam:               Thanks Kelly. That makes so much sense. What I really appreciated about the paper as well is that they gave us practical thresholds through their receiver operating characteristic analyses. Just for everyone to know, the threshold value for stroke volume index was 38 mils per minute per meter square, right? And the right atrial pressure threshold was 9 mils of mercury. These are sort of very important, 38 and 9, and practical to keep in mind. Really appreciate that Jason.                                                 The other thing that struck me is these are just very much saying that right ventricular function is important. Is it not, Jason? Dr. Jason Weatherald:   Yeah, I agree. I think that's one of the interesting insights from the study is that we focused mostly on the cardiac index, but it can be misleading in certain patients like Kelly said who perhaps do respond to therapy by increasing the cardiac index but predominantly through increased heart rate. That can be somewhat misleading if you don't really step back and look at it.                                 What I found interesting, too, is that when we looked at subgroups of patients who, in the clinic, you generally think are low risk patients who had good six-minute walk distance, very few symptoms NYHA functional class I or II, and had a cardiac index above the current recommended target of 2.5, that there was almost a third of patients with a low stroke volume index in that category and that seemed to be the majority of patients who died over long-term follow-up within five years.                                                   I think that's really telling about the importance of right ventricular function and just looking at the cardiac index itself can perhaps mislead you if you don't take all of those other factors into consideration. Dr. Carolyn Lam:               Yeah, that's just such a great point and important. That even those classified that we would not have picked up as high risk are the usual measures that we look at. If you look at stroke volume index, they still distinguish those who do better than those who do worse. This is something that was also highlighted, I think, in the accompanying editorial, Kelly, that you invited by Lewis Rubin from New York.                                                 Kelly, what do you think are the real take home messages from this? Dr. Kelly Chin:                    I think he does make a big point that the functional status of the right ventricle is a primary goal of therapy, and that we should definitely be paying attention to it and that there's more than one way to do this. There's the hemodynamic measurements, there's also exercise capacity and functional class, which really do associate with how well the right heart is functioning, both at rest and exercise. I think he also comes back to the serial measurements and the importance of reassessment. Dr. Carolyn Lam:               Yeah, as you had also so elegantly summarized earlier. But, a quick question to both of you. What do we do now about other measures of right heart function? I mean, magnetic resonance imaging seems to be used increasingly for this. Where does this fall in? And what does this say about the routine clinical parameters that we usually look at, like six-minute walk? Jason? Dr. Jason Weatherald:   I have a couple points on that. Number one, I fully agree and our results are really in keeping with the previous smaller studies looking at cardiac magnetic resonance and showing the importance of the stroke volume on imaging. From personal experience, although MR is wonderful, there's a good population of patients who don't really tolerate MR, especially for serial measurements, and there's other contraindications, so I think hemodynamics will continue to fill an important role and are still useful in the patient where you can't figure out exactly what's going on and why they're getting worse.                                                 At this point, I think it's complementary and certainly I think there's some centers in many countries that don't have cardiac MR widely accessible, especially for serial follow-ups, so I think they're really complementary and that our results support imaging studies.                                                 I would say the next thing about the study is that, in the multi variable models that exercise distance, the six-minute walk distance and functional capacity remained independent predictors, so I think, it just highlights the importance and the robustness of these measures, even though NYHA functional class is subjective, it remains a very powerful predictor at baseline and during follow-up. To me, it speaks to the importance of looking at multiple parameters and coming to a multidimensional assessment of risk and PAH and not focusing on one particular variable for making decisions in the clinic. Dr. Kelly Chin:                    I definitely agree with the multidimensional look at a patient function and heart and catheterization. What I was going to say was I also liked, Jason, the use of "complementary" when talking about catheterization and MRI. I see MRI filling a similar niche to echo for many patients. I think if you get an echo and it looks great, heart size is good, heart function is good, I don't see a whole lot of reason to add an MRI, too. We're always routinely doing catheterizations, at least early post treatment, to reassess.                                                 But I do see a role for MRI in some of our patients who are doing not well at all, but we're not quite sure if they're doing poorly enough that it's time for transplant, and I'm trying to decide if the RV is growing or not. It's clearly big, but is it getting bigger each six months that we're looking at it? Sometimes MRI just seems to provide so much more precision than we can get with echo and certainly you're not getting any of those types of measures off of your catheterization. Dr. Carolyn Lam:               Maybe one last question Jason. It's so interesting. What is the future? What are the gaps that you're looking to fill at the moment? Dr. Jason Weatherald:   Ideally, I think it would be a noninvasive way to look at the right ventricle that is cheap, reproducible, and gives us the same confidence that invasive hemodynamics do. Although I find echo is indispensable and MRI is very useful, I think at the end of the day, we all go back to the right heart catheterization and we need to find something that can replace that, but give us the same confidence in what we think we're measuring and that it reflects treatment changes and clinical worsening. Dr. Carolyn Lam:               And Kelly, what do you think should be next steps? Dr. Kelly Chin:                    I have to say I really liked this study. I thought it moves us forward in assessment of prognosis for this population of patients in a really big way. It was large and included a large number of measures that were done very carefully. You always want to see replication.                                                 But, what I'd also like to see is the other forms of pulmonary arterial hypertension. You know this focused mainly on the idiopathic PAH patients, so what happens in connective tissue disease, and also what happens late after treatment, because I think we sometimes see a little bit of a different phenotype in patients that we've treated for many years and sometimes hemodynamics have improved, but in different ways than what we see early on with initial therapies. Dr. Carolyn Lam:               You've been listening to Circulation on the Run. Tune in again next week.  

  Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. I'm Dr. Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Our feature discussion today is about the validation of a novel biomarker-based stroke risk score for atrial fibrillation, the ABC stroke score. But first, here's your summary of this week's journal.     The first paper provides experimental insights into endothelial nitric oxide synthase uncoupling in endothelial dysfunction. In this paper by first author Dr. Lee, corresponding author Dr. Wong and colleagues from Qilu Hospital of Shandong University in China, authors assessed endothelial function in animal models of hyperglycemia, hyperhomocysteinemia, and a dyslipidemia. They demonstrated that GTP cyclohydrolase 1 is the target of the microRNA-133a and that it's a topic expression and endothelial cells mediates endothelial dysfunction.     Furthermore, Lovastatin up-regulated GTP cyclohydrolase 1 and tetrahydrobiopterin and re-coupled endothelial nitric oxide synthase in stress endothelial cells. These actions of Lovastatin were abolished by enforced micro RNA 133A expression and mirrored by a mir-133a-antagomir. Finally, the beneficial effect of Lovastatin in mice were abrogated by in vivo mir-133A over-expression or by GTP cyclohydrolase 1 knockdown. In summary, this paper offers a mechanistic basis for targeting micro RNA 133A as a therapeutic approach to correct endothelial nitric oxide synthase dysfunction. It also provides further support to the role of statins in combating endothelial dysfunction.     The next study shows us that in hypertrophic cardiomyopathy, calcium mishandling may be the potential link between the primary genetic cause and downstream signaling cascade that leads to hypertrophy and arrythmias. In this study, Dr. Helms and colleagues from University of Michigan analyzed gene expression, protein levels and functional essays for calcium regulatory pathways in 35 human hypertrophic cardiomyopathy surgical samples with and without sarcomere mutations and compared that with 8 control hearts. They found a marked reduction in circa2 abundance, which correlated with reduced circa2 function in hypertrophic cardiomyopathy compared to controlled hearts regardless of the underlying genetic etiology.     However, calcium calmodulin depend protein kinase type 2 or cam2, which is a calcium sensing kinase, was deferentially activated only in the sarcomere gene mutation positive samples. Activation of chem kinase 2 was associated with an increase in phospholamb and phosphorylation in hypertrophic cardiomyopathy. However, neither calcineurin MRNA nor MEF2 activity was increased, suggesting that calcineurin pathway activation was not an upstream cause of increased chem kinase 2 protein abundance or activation.     In summary, this paper demonstrated that calcium mishandling occurs through both genotype specific and common pathways in human hypertrophic cardiomyopathy. Post-translational activation of chem kinase 2 pathway is specific to sarcomere mutation positive hypertrophic cardiomyopathy. While Sarco 2 abundance and sarcoplasmic reticulum calcium uptake are depressed in both sarcomere positive and negative hypertrophic cardiomyopathy. Thus, chem kinase pathway inhibition may improve aberrant calcium cycling in hypertrophic cardiomyopathy. This is discussed further in an accompanying editorial by Dr. Jill Tardiff.     The third study suggests that in patients with a dilated aortic route and trileaflet aortic valve, a ratio of aortic route area to height provides independent and improved stratification for prediction of death. First author Dr. Masry, corresponding author Dr. Desai and colleagues from the Center for Aortic Disease, Heart and Vascular Institute of Cleveland Clinic, studied consecutive patients with a dilated aortic route of greater or equal to 4 centimeters who underwent echocardiography and gated contrast enhanced thoracic aortic computer tomography or magnetic resonance and geography between 2003 and 2007.     A ratio of aortic route area over height was calculated on tomography and a cutoff of 10 squared centimeters per meter of height was chosen as abnormal. In 771 patients with trileaflet aortic valve and concomitant aortopathy, there was incremental prognostic value for indexing aortic route or ascending aortic area to patient height rather than using an unindexed aortic diameter. Incorporation of the ratio significantly and independently reclassified the risk for death and at normal ratio was independently associated with higher long-term mortality while cardiovascular surgery was associated with improved survival. Importantly, a sizable minority of patients with aortic route diameters between 4.5 and 5.5 centimeters had an abnormal aortic route when indexed to height ratio. 78 percent of deaths in this subgroup occurred in those with an abnormal aortic route area to height ratio. Findings were similar when ascending aortic measurements were considered. The take home message is that an aortic route area to height ratio above 10 squared centimeters per meter of height has significant and independent prognostic utility and may be used to re-stratify patients with trileaflet aortic valve and a dilated aorta.     The final study provides pre-clinical data to show that Ticagrelor reduces cardio damage post myocardial infarction to a greater extent than Clopidogrel by an adenosine induced organ protective response. First author Dr. Villaher, corresponding author Dr. Bademan and colleagues from the Cardiovascular Research Center in Barcelona, Spain studied a close-chest swine model of ischemia reperfusion in which myocardial infarction was induced by 1 hour balloon occlusion of the mid-left anterior descending coronary artery followed by 24 hours of re-flow. Prior to occlusion, the animals were randomly assigned to receive either placebo, a loading does of Clopidogrel, a loading does of Ticagrelor or a loading does of Ticagrelor followed by an A1 A2 receptor antagonist. Edema infarc size left ventricular size and left ventricular function were assessed by three T cardiomagnetic resonance imaging. Inhibition of platelet aggregation was the same between the groups receiving a P2Y-12 inhibitor.     Yet, Ticagrelor reduced infarc size to a significantly greater extent than Clopidogrel, reducing it by a further 23.5 percent, an effect supported by troponin eye assessment and histopathological analysis. Furthermore, compared to Clopidogrel, Ticagrelor significantly diminished myocardial edema by 24.5 percent, which correlated with infarced mass. Administration of an adenosine A1 A2 antagonist abolished the cardio protective effects of Ticagrelor over Clopidogrel. At a molecular level, aquaporin 4 expression decreased and the expression and activation of AMP kinase cyclin and COX-2 increased in the ischemic myocardium of Ticagrelor versus Clopidogrel treated animals. In summary, this study shows that Ticagrelor exerts cardio protective effects beyond its anti-platelet efficacy by adenosine dependent mechanisms, which reduce necrotic injury and edema formation. This is discussed in an accompanying editorial by Drs. Gerbel, Jung and Tantry. That wraps it up for the summaries. Now for our feature discussion.     Today, we are going to be discussing the performance of the ABC score for stroke in atrial fibrillation. And as a reminder for all our listeners there, ABC stands for A for age, B for biomarkers, that's NT-proBNP and high-sensitivity troponin, and C for clinical history of prior stroke. And again as a reminder, this risk score was originally derived in the Aristotle trial. However, we have new results about its performance and validation today from first and corresponding author Dr. Jonas Oldgren from Uppsala Clinical Research Center in Sweden. Welcome, Jonas.   Speaker 2: Thank you very much.   Carolyn Lam: We also have today the associate editor who managed this paper, Dr. Sandeep Das from UT Southwestern. Hi Sandeep.   Speaker 3: Hi Carolyn, thanks for having me.   Carolyn Lam: So Jonas, could you start off by telling us why you did this study and what you found?   Speaker 2: We did this study to validate the recently derived ABC stroke risk score. We have had risk scores for predicting stroke in patients with atrial fibrillation derived since the late 1990's and refined later on. But those risk scores have only used clinical markers for risk. We have for several years developed new risk prediction models with biomarkers and now we are combine them in a very simple biomarker based risk score, taking into account age as a clinical variable and the clinical history of prior stroke and only two common used biomarkers. And by that we can predict the risk of stroke with better precision than previous clinical risk scores.   Carolyn Lam: Yeah, I like what you said. I mean it is literally as simple as ABC. So tell us how you validated it and what you found.   Speaker 2: It was derived in a large cohort of patients participating in a clinical trial with new or relapsed coagulant compared to Warfarin and we now validated in almost a full size group participating it another clinical trial. So we have large data sets of very well described patients where we have good outcome data. Very solid data to rely on. Now we can see that the ABC risk score is now validated but the good precision and good collaboration of the discriminatory abilities is high and better than the previously used clinical risk scores.   Carolyn Lam: Could you give us some numbers behind that that are clinically meaningful? Everyone's going to be wondering compared to the chads-vasc score for example, how does this ABC score perform in that validation test set?   Speaker 2: We can adjust that by several different aspects. One is of course to calculate the C index which is a statistical method to see how good we can predict risk and the C indices for the ABC stroke score both in the duration and now in the validation cohort is higher than for the chads-vasc and atrial risk scores. But we can also look at what we have in this paper in circulation ... we can look at predicted outcome rates and observed outcome rates and can see that they clearly overlap both in the duration and validation court. So if you predict a risk that is less than 1 percent per year, it is observed also a risk that is less than 1 percent a year. Does this always ... the thing is when you derive risk or but when you validate it in another cohort, you need to show that it's a similar result.   Carolyn Lam: Yeah, that's true. Sandeep, you are managing this paper. It's very important. How do you think that clinicians should be taking the results?   Speaker 3: I think that clearly using anticoagulation and selected patients at high risk for stroke with atrial fibrillation is one of the best things we do in cardiology. You know in terms of reducing the risk of an important harm to patients. I think there's a fair bit of dissatisfaction out there with currently sort of standard, which is chads-vasc. Especially in people with a chads-vasc ... men with a chads-vasc of 1 or women with a chads-vasc of 1 to 2 where there's a bit of struggling over how to decide. So I think that one real advantage of this score in addition to the fact that it predicts better by the higher C statistic, which is fantastic and pretty uncommon, right? Lars sort of buried the lead a little bit by not emphasizing that it's relatively rare that we're able to move a c statistic by a point of 5 in the modern era.     But the other thing is that it helps give us an ability to come up with good estimates in people at low risk, which I think has been a challenge and something that people are a little concerned clinically. So I think that this is easily available, biomarkers that we routinely check all the time and it doesn't have the sort of gender challenge with chads-vasc where you're trying to figure out whether your low risk woman really needs to be on Warfarin or anticoagulation. So I think that it has a lot of clinical utility right out of the box, which is nice.   Carolyn Lam: Actually, Jonas could you let us know is there any sex differences in the performance of the score?   [00:14:46] Speaker 2:   There are no differences in the performance of the score. So we looked ... the advantage of this score is when we derived it in the original model, we looked at all important clinical and biomarker risk factors and we can see that these were the foremost interesting markers. So we only used those. So we can predict much better and as pointed out so nicely by Sandeep, for patients at the lower end of the risk spectrum, we can find patients or have higher or lower risk even within patients with chads-vasc 1 or chads-vasc 2. And I think it's also important to see what about patients at higher risk despite proper anticoagulation. We did not know how to treat them but in the future we might perhaps tailor treatment also for those patients with residual high risk of stroke despite proper anticoagulation treatment. For instance, if the left atrial appendage occluded devices are shown in the future to be a good option for those patients, we can find them also by this risk score. So both in the higher and lower end of the risk spectrum.   Carolyn Lam: That's a really good point. On that note, I'm just curious. What do you think is in the future? What more knowledge do we need to address before we put this into practice or are you already using this? Or do you think it should enter guidelines for example? Maybe Sandeep, I could ask for your opinion first.   Speaker 3: We see a lot of biomarkers associated with increased risk kind of studies come out in the literature. You know probably every week you see several of these things come out. So what's really interesting about this is that it's obviously methodologically extremely well done but its been derived and validated in two large cohorts, which is pretty much best practice right? You want to see people validate these risk scores in large and distinct cohorts of patients to build up sort of clinical validity to the reader or consumer. So I think, from my standpoint, this is ready for prime time. I'm really intrigued by the fact that biomarkers, especially troponin, are predicting stroke in this population and there have been some observational reports out there that have showed an association between troponin and increased risk of stroke or worse outcomes after stroke. So I'd be really curious as to what Jonas thinks about why troponin would be predictive of stroke in this population.   Speaker 2: We were extremely intrigued by the finding when we first did those single observations of only troponin as a risk marker because we know that troponin is a very specific protein found in the myocardium. But the clinic predicts risk for stroke also and there are several explanations but they are mainly hypotheses about aging and myocardial function really to identify patients of risk. But the clear cut explanation is still not there.   Carolyn Lam: It's likely that these biomarkers are incorporating aspects that we don't fully understand, which is why they are better predictors isn't it? I mean to your point Sandeep.   Speaker 3: Yeah, no absolutely. And I think that's great.   Carolyn Lam: Exactly. It really opens a lot of other questions that need to be answered in the meantime. Jonas, any other last words about how you may be applying this clinically in your own patients?   Speaker 2: We have no solid data supporting the use of this clinical risk score and as already pointed out, which I think is very good, all clinic risk scores should of course be in the best world validated as useful decision support truth and really in clinics trial seeing that they improve outcomes. This is to my knowledge never been down with a clinical risk scores. We have never used them prospectively to guide treatment and to improve outcomes. Actually, we are aiming to do that. We hope to start a clinical trial next year with ABC score guided treatment compared to standard of care. But it's a very huge undertake of course to that we can improve treatment by risk or guided management.   Carolyn Lam: That's excellent. So remember everyone, you heard it right here. A new trial that they're engaging. I really congratulate you first for this study, as well as this future efforts which are clearly going to be very important.     Thank you very much both of you for joining us today and thank you listeners for listening. Don't forget to tune in next week.  

We're back and better than ever with a NEW host! This season, Kieran Quinn takes the reigns and is excited to bring you the latest and greatest in the world of emerging clinical evidence. Along outgoing host Amol Verma, the two hosts discuss two studies: Just how dangerous are opioids in the treatment of chronic pain ...The post REPLAY – Drugs on the Brain: Opining on Opioid-Induced Death and Ticagrelor for TIA or Stroke appeared first on Healthy Debate.

We’re back and better than ever with a NEW host! This season, Kieran Quinn takes the reigns and is excited to bring you the latest and greatest in the world of emerging clinical evidence. Along outgoing host Amol Verma, the two hosts discuss two studies: Just how dangerous are opioids in the treatment of chronic pain ... The post REPLAY – Drugs on the Brain: Opining on Opioid-Induced Death and Ticagrelor for TIA or Stroke appeared first on Healthy Debate.

We're back and better than ever with a NEW host! This season, Kieran Quinn takes the reigns and is excited to bring you the latest and greatest in the world of emerging clinical evidence. Along outgoing host Amol Verma, the two hosts discuss two studies: Just how dangerous are opioids in the treatment of chronic pain ...The post Drugs on the Brain: Opining on Opioid-Induced Death and Ticagrelor for TIA or Stroke appeared first on Healthy Debate.

We’re back and better than ever with a NEW host! This season, Kieran Quinn takes the reigns and is excited to bring you the latest and greatest in the world of emerging clinical evidence. Along outgoing host Amol Verma, the two hosts discuss two studies: Just how dangerous are opioids in the treatment of chronic pain ... The post Drugs on the Brain: Opining on Opioid-Induced Death and Ticagrelor for TIA or Stroke appeared first on Healthy Debate.