Podcasts about Edoxaban

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.

Stay ahead with the newest cardiology research findings that could change your clinical practice! STUDY #1: First up, we explore new data on edoxaban dosage for older patients with atrial fibrillation. If we could give older patients a lower dose of edoxaban to reduce the risk of bleeding, will they still benefit from a lower risk for stroke?  Zimerman, A, Braunwald, E,  Steffel, J, et al. 2024. Dose reduction of edoxaban in patients 80 years and older with atrial fibrillation: Post hoc analysis of the ENGAGE AF-TIMI 48 randomized clinical trial. JAMA Cardiol. Published online. (https://doi.org/10.1001/jamacardio.2024.1793) STUDY #2: Next, we delve into the nuanced world of invasive versus noninvasive treatment of non-ST-segment elevation myocardial infarction (NSTEMI). You'll find out if mortality rates go up when we use a less invasive approach.  Kunadian, V, Mossop, H, Shields, C, et al. 2024. Invasive treatment strategy for older patients with myocardial infarction. N Engl J Med. Published online. (https://doi.org/10.1056/NEJMoa2407791) STUDY #3: Lastly, we break down the latest findings on chelation therapy in patients with stable coronary artery disease and diabetes. Tune it to see whether the latest data challenges your perspective on the efficacy of EDTA in reducing cardiovascular risks. Lamas, GA, Anstrom, KJ, Navas-Acien, A, et al. 2024. Edetate disodium-based chelation for patients with a previous myocardial infarction and diabetes: TACT2 randomized clinical trial. JAMA. Published online. (https://doi.org/10.1001/jama.2024.11463) Join us to uncover these critical insights, discussions, and more. Let's turn data into actionable wisdom and elevate your cardiology practice.  Learn more with Medmastery's courses: ECG Mastery Program (34 CME) Get a Basic or Pro account, or, get a Trial account. Show notes: Visit us at  https://www.medmastery.com/podcasts/cardiology-podcast.

Commentary by Dr. Candice Silversides

MedLink Neurology Podcast is delighted to feature selected episodes from BrainWaves, courtesy of James E Siegler MD, its originator and host. BrainWaves is an academic audio podcast whose mission is to educate medical providers through clinical cases and topical reviews in neurology, medicine, and the humanities, and episodes originally aired from 2016 to 2021. Originally released: July 18, 2017 Long-term antithrombotic treatment of embolic stroke sounds like a tricky field to navigate. Aspirin is the drug of choice in the acute setting for most patients, but when cardioembolic stroke is suspected, aspirin is inferior to anticoagulation for preventing recurrent stroke. In the age of novel oral anticoagulants, why choose warfarin and risk drug interactions, dietary restrictions, and bleeding risk? In this episode, we discuss the pros and cons of each of the major NOACs for secondary stroke prevention. Enjoy! BrainWaves podcasts and online content are intended for medical education only and should not be used to guide medical decision-making in routine clinical practice. Any cases discussed in this episode are fictional and do not contain any patient health-identifying information. REFERENCES Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361(12):1139-51. Erratum in: N Engl J Med 2010;363(19):1877. PMID 19717844Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2013;369(22):2093-104. PMID 24251359Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011;365(11):981-92. PMID 21870978Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365(10):883-91. PMID 21830957 We believe that the principles expressed or implied in the podcast remain valid, but certain details may be superseded by evolving knowledge since the episode's original release date.

Commentary by Dr. Candice Silversides

Jason T. Jacobson, MD, FHRS, of Westchester Med Center-New York Med College discusses Anticoagulation with Edoxaban in Patients with Atrial High-Rate Episodes with Taya Glotzer, MD, FHRS, of Hackensack University Medical Center at Hackensack Meridian Health, and Rod S. Passman, MD, FHRS, of Northwestern University.   https://www.hrsonline.org/education/TheLead   Host Disclosure(s): J. Jacobson: Honoraria/Speaking/Consulting Fee: American College of Cardiology, Zoll Medical Corporation; Research (Contracted Grants for PIs Named Investigators Only): Aboot, Phillips; Stocks (Privately Held): Atlas 5D   Contributor Disclosure(s): T. Glotzer: Honoraria/Speaking/Consulting Fee: Mayo Clinic, Medtronic, Boston Scientific, Abbot, Mediasphere Medical R. Passman: Honoraria/Speaking/Consulting Fee: Medtronic, Janssen Pharmaceuticals, iRhythm Technologies, Boston Scientific; Research (Contracted Grants for PIs Named Investigators Only): AHA Foundation Award, Abbott Medical, NIH/NHLI, Apple Inc; Royalty Income: UpToDate, Inc.

This month we're discussing four papers:   Title: Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity DOI: 10.1056/NEJMoa2306963   Title: Anticoagulation with Edoxaban in Patients with Atrial High-Rate Episodes DOI: 10.1056/NEJMoa2303062   Title: Safety of Switching from a Vitamin K Antagonist to a Non-Vitamin K Antagonist Oral Anticoagulant in Frail Older Patients with Atrial Fibrillation:  Results of the FRAIL-AF Randomized Controlled Trial DOI: 10.1161/CIRCULATIONAHA.123.066485    Title: Dapagliflozin in Patients with Heart Failure and Deterioration in Estimated Glomerular Filtration Rate to

PODCASTER SENIOR: Andrea Zini;PODCASTER JUNIOR: Gabriele Prandin;RAZIONALE: Gli anticoagulanti orali diretti (DOAC) contro il fattore Xa e IIa hanno rivoluzionato le terapie per i pazienti con disturbi trombo-embolici, in particolare il cardioembolismo da Fibrillazione atriale non valvolare. Questa classe di farmaci che comprende Apixaban, Rivaroxaban, Edoxaban e Dabigatran ha dimostrato la sua superiorità nel diminuire il rischio emorragico sistemico ed intracranico e la medesima efficacia nel prevenire eventi ischemici cerebrali se paragonati al warfarin, come confermato da una metanalisi di trial clinici randomizzati pubblicata su Circulation nel 2022 che includeva circa 71000 pazienti. La diffusione di questi farmaci ha comportato però un problema nel trattamento in caso di evento ischemico acuto: essi infatti se associati alla trombolisi, potrebbero teoricamente indurre una complicanza emorragica. Secondo le linee guida ESO 2021, viene raccomandata la valutazione dell'attività anticoagulante pre trattamento per stimare se il farmaco è a concentrazioni terapeutiche o sub terapeutiche, dando quindi la possibilità di eseguire il trattamento trombolitico nel caso in cui fosse sub terapeutico. Nel caso in cui il dosaggio fosse ancora in range, non è completamente chiarito il ruolo dei reversal specifici come l'Idarucizumab (per dabigatran) o Andexanet (per Apixaban e Rivaroxaban).

Commentary by Dr. Candice Silversides

Efficacy and Safety of Intensive Versus Nonintensive Supplemental Insulin With a Basal-Bolus Insulin Regimen in Hospitalized Patients With Type 2 Diabetes: A Randomized Clinical Study | Diabetes Care | American Diabetes Association (diabetesjournals.org)   randomized noninferiority study from Emory University, 224 hospitalized patients with longstanding type 2 diabetes  Both groups received basal/bolus insulin; both the starting dose and subsequent changes were specified by the study protocol. Additional premeal SSI was added to scheduled premeal bolus doses.randomized to either intensive SSI (at BG >140 mg/dL) or nonintensive SSI (at BG >260 mg/dL) before meals and at bedtime.  Mean baseline glycosylated hemoglobin (HbA1c) was 9%, and 60% of patients were using insulin at home. Patients with a presenting glucose level of >400 mg/dL or diabetic ketoacidosis were excluded.  Outcome---Mean daily BG level, hypoglycemia, severe hyperglycemia, percent of BGs in the target range (70–180 mg/dL), and the amount of total, basal, or prandial insulin used did not differ between groups. However, significantly fewer patients in the nonintensive group than in the intensive group received SSI (34% vs. 91%).   COMMENTAlthough this is a single-center study, its results are persuasive and suggest that a less-intense SSI regimen can achieve similar glucose outcomes in hospitalized patients with type 2 diabetes who are receiving basal/bolus insulin. It also could decrease nursing treatment burden. As we move slowly toward more continuous glucose monitoring in hospitals, reducing use of SSI is another opportunity to achieve similar results with less staff burden and more patient comfort.  Comparative Effectiveness and Safety Between Apixaban, Dabigatran, Edoxaban, and Rivaroxaban Among Patients With Atrial Fibrillation: A Multinational Population-Based Cohort Study: Annals of Internal Medicine: Vol 175, No 11 (acpjournals.org) In a retrospective study, investigators accessed five electronic health databases from Europe and the U.S. to compare >500,000 new DOAC users with newly diagnosed atrial fibrillation. Follow up varied from 1.5 to 4.5 years.   In propensity score–adjusted analyses, patients who received apixaban had significantly less gastrointestinal (GI) bleeding did those who received any of the other three drugs (hazard ratios, 0.7–0.8). This result was consistent among older patients and those with chronic kidney disease (CKD). Risk for stroke or other systemic embolism, intracranial hemorrhage, and all-cause mortality did not differ significantly among DOACs.    COMMENTThis is the largest comparison of individual DOACs, and it demonstrates similar efficacy among all agents. Although apixaban was associated with less GI bleeding, absolute percentages of GI bleeds ranged from ≈2% to ≈3.5% for all DOACs; therefore, apixaban's statistically significant safety benefit might amount to marginal clinical benefit for any individual patient. I might turn to apixaban for patients at high risk for GI bleeding (and those with CKD), but all DOACs remain reasonable options for preventing thromboembolism in most patients with atrial fibrillation. Ellenbogen MI et al. Safety and effectiveness of apixaban versus warfarin for acute venous thromboembolism in patients with end-stage kidney disease: A national cohort study. J Hosp Med 2022 Oct; 17:809. (https://doi.org/10.1002/jhm.12926. opens in new tab)  . In an industry-funded retrospective study, investigators used a national database (years, 2014–2018) and propensity score–adjusted analysis to compare outcomes among >11,500 patients with ESRD and newly diagnosed VTE who received either apixaban or warfarin.Only 2% of patients received apixaban in 2014, but 47% received apixaban in 2018.during the 6 months following initiation of therapy, apixaban — compared with warfarin  associated with significantly lower incidence of major bleeding (10% vs. 14%), including intracranial bleeding (1.8% vs. 2.5%) and gastrointestinal bleeding (8.6% vs. 10.4%). Recurrent VTE and all-cause mortality were similar in the two groups.   VTE and creatine clearence less than 30 then I think apixaban is the drug of choice—I would like to see this study don't with afib and done with exclusively

In this podcast, James Cave (Editor-in-Chief) and David Phizackerley (Deputy Editor) talk about the February 2023 issue of DTB. They discuss concerns over a national initiative in England to transfer people with atrial fibrillation to edoxaban from other DOACs (https://dtb.bmj.com/content/61/2/18). They review a study that examined whether the correct dose of DOAC was used in people with renal impairment (https://dtb.bmj.com/content/61/2/21). They talk about the use of empagliflozin in people with heart failure (https://dtb.bmj.com/content/61/2/22) and finish with an overview of an article that discusses prescribing for pregnancy for those with inflammatory rheumatic disease (https://dtb.bmj.com/content/61/2/24). 60th anniversary interview with Dr John Dowden: https://soundcloud.com/bmjpodcasts/dtb-60th-anniversary-podcast-interview-john-dowden Trends in direct oral anticoagulant (DOAC) prescribing in English primary care (2014–2019): https://heart.bmj.com/content/109/3/195 The contact address for the DTB team is dtb@bmj.com. Please subscribe to the DTB podcast to get episodes automatically downloaded to your mobile device and computer. Also, please consider leaving us a review or a comment on the DTB Podcast iTunes podcast page (https://podcasts.apple.com/gb/podcast/dtb-podcast/id307773309). Thank you for listening.

Commentary by Dr. Valentin Fuster

What is clinical problem with regard to leaflet thrombosis after TAVR, and what are the main findings of the ADAPT-TAVR trial? In this interview, Duk-Woo Park, MD and Sun Moon Kim MD, with Zaid I. Almarzooq MBBCh, discuss Late Breaker: Edoxaban Versus Dual Antiplatelet Therapy For Valve Thrombosis And Cerebral Thromboembolism After Transcatheter Aortic-valve Replacement: A Randomized ADAPT-TAVR Trial.

Cardiac arrest care, finerenone, carotids, meds post TAVI: less is more and the new may not be as grand as the tried and true. John Mandrola, MD, provides a third ESC review. To read a partial transcript or to comment, visit: https://www.medscape.com/twic I - Cardiac Arrest Care - Angiography Can Wait for Cardiac Arrest Without ST-Elevation https://www.medscape.com/viewarticle/957471 - Angiography after Out-of-Hospital Cardiac Arrest without ST-Segment Elevation https://www.nejm.org/doi/full/10.1056/NEJMoa2101909 - Coronary Angiography after Cardiac Arrest without ST-Segment Elevation https://www.nejm.org/doi/full/10.1056/NEJMoa1816897 II - Finerenone - FIDELITY: Finerenone Cuts CV Risk in T2D Across CKD Spectrum https://www.medscape.com/viewarticle/957470 - Cardiovascular Events with Finerenone in Kidney Disease and Type 2 Diabetes https://www.nejm.org/doi/full/10.1056/NEJMoa2110956 - Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes https://www.nejm.org/doi/full/10.1056/NEJMoa2025845 III - Carotid Intervention - ACST-2: Carotid Stenting, Surgery on Par in Asymptomatic Patients https://www.medscape.com/viewarticle/957474 - Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy https://doi.org/10.1016/S0140-6736(21)01910-3 IV - Post TAVI DOAC - 'Less Is More' for Edoxaban in Post-TAVI Anticoagulation: ENVISAGE-TAVI AF https://www.medscape.com/viewarticle/957466 - Edoxaban versus Vitamin K Antagonist for Atrial Fibrillation after TAVR https://www.nejm.org/doi/full/10.1056/NEJMoa2111016 - ATLANTIS Hints at How to Choose Post-TAVR Antithrombotics https://www.medscape.com/viewarticle/951234 - A Controlled Trial of Rivaroxaban after Transcatheter Aortic-Valve Replacement https://www.nejm.org/doi/full/10.1056/NEJMoa1911425 Features: - What Are the Implications of ACST-2 for Patients With Asymptomatic Carotid Stenosis? https://www.medscape.com/viewarticle/957502 - Top 5 Studies From ESC 2021 https://www.medscape.com/viewarticle/958598 You may also like: Medscape editor-in-chief Eric Topol, MD, and master storyteller and clinician Abraham Verghese, MD, on Medicine and the Machine https://www.medscape.com/features/public/machine The Bob Harrington Show with Stanford University Chair of Medicine, Robert A. Harrington, MD https://www.medscape.com/author/bob-harrington Questions or feedback, please contact news@medscape.net

In questo podcast si parla dei tempi da rispettare tra la sospensione dei principali farmaci Anticoagulanti, Antiaggreganti e Fibrinolitici e le tecniche di Anestesia Neuroassiale (Anestesia Subaracnoidea o spinale, peridurale, combinata). I tempi di sospensione sono tratti dagli Special Article del 2018: Interventional Spine and Pain Procedures in Patients onAntiplatelet and Anticoagulant Medications (Second Edition)Guidelines From the American Society of Regional Anesthesia and Pain Medicine, the European Society of Regional Anaesthesia and Pain Therapy, the American Academy of Pain Medicine, the International Neuromodulation Society, the North American Neuromodulation Society, and theWorld Institute of Pain (Reg Anesth Pain Med 2018;43: 225–262)Regional Anesthesia in the Patient ReceivingAntithrombotic or Thrombolytic TherapyAmerican Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines (Fourth Edition) (Reg Anesth Pain Med 2018;43: 263–309)I farmaci trattati sono: coumadin, acenocumarolo, eparina non frazionata, eparine a basso peso molecolare, fondaparinux, rivaroxaban, apixaban, edoxaban, dabigatran, eptifibatide e tirofiban, abciximab, clopidogrel, prasugrel, ticagrelor, , cangrelor, ticlopidina, desirudina e bivalirudina, aspirina e i fibrinolitici alteplase e tenecteplase.Questo video costituisce solo uno strumento di studio e di ripasso di un argomento molto mnemonico. Non esaurisce l'argomento. NON SOSTITUISCE IL PARERE DI UN MEDICO. È dedicato a tutti gli Specializzandi di Anestesia, Rianimazione, Terapia Intensiva e del Dolore.

Commentary by Dr. Valentin Fuster

Paul J. Wang: Welcome to the monthly podcast, On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, Editor-in-chief, with some of the key highlights from this month's issue. In our first paper, Zak Loring and associates examined 3,139 patients undergoing atrial fibrillation (AF) ablation, between 2016 and 2018 in the Get With The Guidelines-Atrial Fibrillation Registry from 24 US centers. Patients undergoing AF ablation were predominantly male (63.9%) and Caucasian (93.2%) with a median age of 65. Hypertension was the most common comorbidity (67.6%), and persistent atrial fibrillation patients had more comorbidities than paroxysmal AF patients. Drug refractory, paroxysmal AF was most common ablation indication (class I, 53.6%) followed by drug refractory, persistent AF (class I, 41.8%). Radio-frequency, RF ablation, with contact force sensing was the most common ablation modality (70.5%) and 23.7% of patients underwent cryoballoon ablation. Pulmonary vein isolation was performed in 94.6% of de novo ablations. The most common adjunctive lesion included left atrial roof or posterior/inferior lines and cavotricuspid isthmus ablation. Complications were uncommon (5.1%) and were life-threatening in 0.7% of cases. In our next paper, Brian Howard and associates hypothesize that pulse field ablation (PFA) would reduce pulmonary vein stenosis risk and collateral injury compared to irrigated radiofrequency ablation (IRF). IRF and PFA deliveries were randomized in eight dogs with two superior pulmonary veins (PVs), ablated with using one technology and two inferior PVs ablated with the other technology. IRF energy (25-30 watts) or PFA with delivered (16 pulse trains) at each PV in a proximal and in a distal site. Contrast computed tomography (CT scans) were collected at 0, 2, 4 and 8, and 12 week, including termination time points to monitor PV cross-sectional area at each PV ablation site. Maximum average change in normalized cross-sectional area at 4 weeks was 46.1%±45.1% post IRF compared to -5.5±20.5% for PFA (P≤ to 0.001). Necropsy showed expansive PFA lesions without stenosis in the proximal PV sites compared to more confined and often incomplete lesions after IRF. At the distal PV sites only IRF ablations were grossly identified based on focal fibrosis. Mild pulmonary chronic parenchymal hemorrhage was noted in three left superior pulmonary vein lobes after IRF. Damage to vagus nerves, as well as evidence of esophagus dilation, occurred at sites associated with IRF. In contrast, no lung, vagal nerve, or esophageal injury was observed at PFA sites. In our next paper, Mohamed Diab and associates aimed to assess the safety of ablation for atrial fibrillation (AF) with trans-esophageal (TEE) screening on intracardiac echocardiography (ICE) imaging of the appendage in direct oral anticoagulant (DOAC) compliant patients. They studied 900 patients with a medium CHA2DS2-VASc score of two. Interquartile range one to three. All consecutive patients presenting with AF or atrial flutter on DOAC were included. All were on DOACs (333 Rivaroxaban, 285 Dabigatran, 281 Apixaban and one Edoxaban). Thromboembolic complications occurred in four patients (0.3%), two ischemic strokes, one transient ischemic attack without residual deficit and one splenic infarct, all with no further complications. Bleeding complications incurred in 5 patients (0.4%), including 2 pericardial effusions (1 intraoperative, 1 after 30 days, both drained), and 3 groin hematomas (1 due to needing heparin for venous thrombosis, none requiring intervention). No patients required emergent surgeries. In our next paper, Alexios Hadjis and associates aim to explore the role of complete diastolic pathway activation mapping on ventricular tachycardia (VT) recurrence. They studied 85 consecutive patients who underwent VT ablation using and guided by high-density mapping. During activation mapping, the presence of electrical activity in all segments of diastole defined the evidence of having had recorded the whole diastolic interval. Patients were categorized as having recorded the full diastolic pathway, partial diastolic pathway or no diastolic pathway map performed. Recurrences of VT were defined as appropriate IC therapies or on the basis of EC documented arrhythmia. Complete recording of the diastolic pathway was achieved in 36 of 85 (42.4%). Partial recording of the diastolic pathway of clinical VT was achieved in 24 of 85 (28.2%). No recording of the diastolic pathway of clinical VT was feasible in 25 of 85 patients (29.4%). At a mean of 12.8 months, freedom from VT recurrences was 67% in the overall cohort. At a mean of 12.8 months, freedom from VT recurrence was 88% in patients who had full diastolic activity recorded, 50% of partial diastolic activity recorded and 55% in those who underwent substrate modification (P=0.02). The authors concluded that mapping of the entire diastolic pathway was associated with a higher freedom from VT occurrence compared to partial diastolic pathway recording and substrate modification. The use of multielectrode mapping catheters in recording diastolic activity may help predict those VTs employing intramural circuits and further optimize ablation strategies. In our next paper, Hui-Nam Pak and associates investigated whether electrical posterior box isolation (POBI) may improve rhythm outcome of catheter ablation in patients in whom persistent atrial fibrillation changes to paroxysmal atrial fibrillation after antiarrythmic drug medication and cardioversion. They prospectively randomized 114 patients, 75% male, 59.8 years old to circumferential pulmonary vein ablation (CPVI) alone (n=57) and an additional POBI group (n=57). Primary endpoint was AF recurrence after a single procedure, and secondary endpoints were recurrence pattern, cardioversion rate and response to antiarrhythmic drugs (AAD). After a mean follow-up of 23.8 months, the clinical recurrence rate did not significantly differ between the CPVI alone and additional POBI group (31.6% versus 28.1%; P=0.682). The recurrence rate as atrial tachycardias, 5.3% versus 12.3% (P=0.14) and cardioversion rates, 5.3% versus 10.5% (P=0.25) were not significantly different between the CPVI and POBI group. At the final follow-up, sinus rhythm was maintained without antiarryhthmic drug in 52.6% of CPVI group and 59.6% of the POBI group (P=0.45). No significant difference was found in major complications between the two groups, 5.3% versus 1.8% (P=0.618). But the total ablation time was significantly longer in the POBI group (4187 seconds versus 5337 seconds; P

Dr. Ebell and Dr. Wilkes discuss the POEM titled ' Low-dose edoxaban effective for stroke prevention for elderly patients with atrial fibrillation '

With Renato Lopes, Duke Univ. Medical Center - U.S. and Alexander Fanaroff, Univ. of Pennsylvania - U.S. Link to EHJ paper

Episode 23: Blood Clots: DVTThe sun rises over the San Joaquin Valley, California, today is August 14, 2020. Pain relief is a task that always keeps doctors very busy, especially if pain relief can be accomplished by a medication that is easily-administered, given at a convenient frequency, with no adverse effects, and with no addiction potential (specially to fight the so-called “opioid epidemic”). And if that medication contributes to healing the pain-causing condition, then that’s a perfect medication for pain relief. As a result of that endless search for a perfect pain reliever, the University of Southern California Health Sciences presented a new study on July 13, 2020, revealing that kappa opioids, a significantly less addictive opioid, may both preserve cartilage in joints and also ease pain in osteoarthritis (1). Sorry UCLA, we have to accentuate the positive regardless of the source. Go Bruins!  On August 11, 2020, we woke up to the news that Russia’s government registered the first COVID 19 vaccine in the world. President Vladimir Putin stated that his own daughter was inoculated with the vaccine and “she is feeling well and has high number of antibodies”. While some celebrated the Russian “big step for humanity”, some experts expressed concerns about safety, including the World Health Organization, warning Russia to adhere to standard protocols for testing a vaccine (2). Coronavirus has brought more than a disease to the world, it has brought extensive material for political debate and controversy. There is a joke that circulated in social media that may be relevant in this case: A patient asks her doctor, “When will this coronavirus be over?”, and the doctor answers, “I don’t know, I’m not that involved in politics”. We hope humanity steps up and joins forces to overcome this devastating disease.____________________________Welcome to Rio Bravo qWeek, the podcast of the Rio Bravo Family Medicine Residency Program, recorded weekly from Bakersfield, California, the land where growing is happening everywhere.The Rio Bravo Family Medicine Residency Program trains residents and students to prevent illnesses and bring health and hope to our community. Our mission: To Seek, Teach and Serve. Sponsored by Clinica Sierra Vista, Providing compassionate and affordable care to patients throughout Kern and Fresno counties since 1971. ____________________________“[As doctors, let’s], never forget that we have the opportunity to do more good in one day than most people have in a month."― Dr. Suneel DhandDear residents, how many opportunities did you have to do good today? It’s a great privilege to be instruments to relief pain, find a solution, and bring peace and happiness to your fellow men. It’s really a privilege. We have today an experienced doctor with whom I’ve had multiple conversations, and I’m very happy for having him in our residency program. Welcome, Dr Gonzalez.Question Number 1: Who are you? My name is Alejandro Gonzalez Perez, I am a second-year resident in the Rio Bravo Family Medicine Residency Program here in Clinica Sierra Vista, Bakersfield, California. I was born in Cuba where I finished medical school and completed a medical residency in Family medicine, and then a residency in Radiology. I am a father of three children, two boys and one girl. I enjoy spending time with my family and friends. My favorite music: Latin music. Favorite sport: I like to go to the gym but I enjoy seeing martial art combats. Favorite movies: action, fiction, and martial arts.Comment: I recently watched The Karate Kid in Netflix, it’s a good show, and they’ll have a sequel in Netflix this month with the same actors of the original movie. Question number 2: What did you learn this week?Currently I’m on the Cardiology rotation. My number one goal in this rotation is optimize treatment for patients in the inpatient and outpatient settings. For example, I am learning how to better handle medication for Heart failure, CAD, HTN, and arrhythmias. And, almost all the patients have combined diagnosis, so you need to select the appropriate medication for HF with CAD, or HF combined with CAD and HTN, or HF with Afib, etc. In addition, my knowledge about diagnostic tests has improved, ECG, Echocardiogram, Cardiac Cath, troponin management. Also, I have learned how to improve the interactions between different services in the hospital. I hadn’t had a previous rotation with Internal Medicine, but in this rotation, I’m spending time with some IM residents, and it’s been positive for me.Venous thromboembolism (VTE)VTE refers to a blood clot that starts in a vein. It is the third leading vascular diagnosis after heart attack and stroke, affecting between 300,000 to 600,000 Americans each year. The mos common presentations are: Deep vein thrombosis (DVT) of the lower extremity and pulmonary embolism (PE). PathophysiologyThe Virchow's triad proposes that VTE is a result of three conditions: Alterations in blood flow (i.e., stasis), Vascular endothelial injury, and Alterations in the constituents of the blood.The causes of venous thrombosis can be divided into two groups: hereditary and acquired.Hereditary causes: Factor V Leiden mutation, Prothrombin gene mutation, Protein S deficiency, Protein C deficiency, Antithrombin deficiency.Acquired risk factors: Prior thrombotic event, recent major surgery, presence of a central venous catheter, trauma, immobilization, malignancy, pregnancy, the use of oral contraceptives or heparin, myeloproliferative disorders, antiphospholipid syndrome (APS), and a number of other major medical illnesses. Of note, a special risk factor is the s-called “Sitting Disease” which, broadly speaking, is defined as a condition of increased sedentary behavior associated with adverse health effects.Provoked vs Unprovoked DVTThe term unprovoked deep vein thrombosis (DVT) implies that there is not an evident cause for DVT. In contrast, a provoked DVT is usually caused by a known event.Proximal vs Distal DVTProximal DVT is located in the popliteal, femoral, or iliac veins. Isolated distal DVT has no proximal component, it is located below the knee, and is confined to the calf veins (peroneal, posterior, anterior tibial, and muscular veins)Symptomatic vs Asymptomatic DVTSymptomatic DVT refers to the presence of symptoms that usually leads to the radiologic confirmation of DVT, whereas asymptomatic DVT refers to the incidental finding of DVT on imaging in a patient without symptoms (eg, computed tomography).Symptoms of DVTThrobbing or cramping pain in 1 leg (rarely both legs), usually in the calf or thigh.Swelling in 1 leg (rarely both legs)Warm skin around the painful area.Red or darkened skin around the painful area.Swollen veins that are hard or sore when you touch them. Diagnosis of DVTDuplex ultrasonography: It can detect blockages or blood clots in the deep veins.  It is the standard imaging test to diagnose DVT. Comment: Yeah! for POCUS in clinic?D-dimer: It rules out DVT if it is negative.Contrast venography: Dye is injected into a large vein in the foot or ankle deep veins in the leg and hip.  It is the most accurate test for diagnosing blood clots but it is an invasive procedure, for that reason, this test has been largely replaced by duplex ultrasonography, and it is used only in certain patients.Magnetic resonance imaging (MRI) and computed tomography (CT) scan. These tests can provide images of veins and clots, but they are not generally used to diagnose DVT.Treatment of DVTAnticoagulants: Anticoagulation (commonly referred to as “blood thinners”) is the mainstay of therapy for patients with deep vein thrombosis (DVT). Anticoagulation is indicated for all patients with proximal DVT and select cases of distal DVT. To decide on anticoagulation, we must weigh the benefits versus the risk of bleeding. The primary objective of anticoagulation is the prevention of further thrombosis and of early and late complications. Major early complications of DVT include clot extension, pulmonary embolism (PE), major bleeding (from anticoagulation), and death. Late complications include recurrent clot, post-thrombotic (post phlebitic) syndrome, and chronic thromboembolic pulmonary hypertension. The most frequently used injectable anticoagulants are: unfractionated heparin (IV), Low molecular weight heparin (LMWH) (SQ), and Fondaparinux (SQ). Anticoagulants that are taken orally (swallowed) include Warfarin and NOACs: Dabigatran, Rivaroxaban, Apixaban, and Edoxaban. All of the anticoagulants can cause bleeding, so people taking them have to be monitored to prevent unusual bleeding. Monitoring can be with INR (Warfarin) or clinically (NOAC). Thrombolytics: Thrombolytics (commonly referred to as “clot busters”) work by dissolving the clot. They have a higher risk of causing bleeding compared to the anticoagulants, so they are reserved for severe cases. Inferior vena cava filter: When anticoagulants cannot be used or don’t work well enough, a filter can be inserted inside the inferior vena cava (a large vein that brings blood back to the heart) to capture or trap an embolus (a clot that is moving through the vein) before it reaches the lungs. Thrombectomy/Embolectomy: In rare cases, a surgical procedure to remove the clot may be necessary.  Thrombectomy involves removal of the clot in a patient with DVT.   Embolectomy involves removal of the blockage in the lungs caused by the clot in a patient with PE.  Question number 3: Why is that knowledge important for you and your patients?In primary practice, we encounter patients with symptoms that may be suspicious for DVT. We must be able to diagnose and treat these patients in a timely manner to prevent further complications. DVT is just below MI and stroke in frequency.Question number 4: How did you get that knowledge?I got interested in this topic because of many previous patients I had with this condition. I investigated multiple sources, including, of course, Up to Date, Medscape, but this knowledge has been accumulated over the years of study.Question number 5: Where did that knowledge come from?Up to Date, Medscape, Family Practice Notebook, and Epocrates.____________________________Speaking Medical: Phlegmasia cerulean dolensby Dr. Valerie CivelliPhlegmasia cerulea dolens means “painful blue inflammation”. It is an uncommon but severe form of DVT which results from extensive blockage by a thrombus of the major and the collateral veins of an extremity. This phenomenon was discovered by Jonathan Towne a vascular surgeon in Milwaukee, USA. Phlegmasia cerulea dolens (PCD) is a precursor of frank venous gangrene. It is characterized by severe swelling, cyanosis and blue discoloration. The next time you look down at a leg that appears like it’s from the blue man group in Las Vegas or appears smurf-like, think of Phlegmasia cerulea dolens.  ____________________________Espanish Por Favor: Coáguloby Dr Valerie CivelliCoágulo may be a word difficult to pronounce, but it is very important in the context of DVT, MI, or stroke. You may guess what coágulo means by remembering the word anticoagulant. Yes, coágulo means blood clot. “Señor Pérez, usted tiene un coágulo en las piernas” means “Mr Perez, you have a blood clot in your legs”. Coágulo may be used by a patient who also has blood clots in her menstrual period during an episode of menorrhagia or during other excessive bleeding. Now you know the Spanish word of the week: Coágulo.____________________________For your Sanity by Drs. Steven Saito, Gina Cha, and Alyssa Der MugrdechianWhat’s black, long and hangs from an a*hole? A stethoscope.--Patient: Doctor, my son ate a firefly!--Doctor: Why did he do that?--Patient: He wanted a light snack. --Patient: Doctor, doctor, I’ve had a terrible stomachache after eating tamales.--Doctor: Were they fresh?--Patient: I don’t know, how can you tell?--Doctor:  How did they look when you removed the corn husk?--Patient: Were you supposed to remove the corn husk?Now we conclude our episode number 23 “Blood Clots: DVT”. Dr Gonzalez explained the basics of Deep Venous Thrombosis (DVT) and reminded us that DVT can be easily diagnosed by ultrasound, and that timely treatment prevents acute and chronic complications. Phlegmasia cerulean dolens is just another way to say “painful blue inflammation”, a severe type of DVT that occurs when the MAJOR and COLATERAL veins in a limb are occluded; then, were given the advice by Dr Civelli to recall the word anticoagulant to remember the Spanish word coágulo (blood clot). And we cannot finish this episode without mentioning the name of the first registered COVID-19 vaccine. It’s called Sputnik V. We tried several times to record that name in the intro, but we could not stop laughing. We honestly hope the Sputnik V is a great success regardless of its amusing name.This is the end of Rio Bravo qWeek. We say good bye from Bakersfield, a special place in the beautiful Central Valley of California, United States, a land where growing is happening everywhere.If you have any feedback about this podcast, contact us by email RBresidency@clinicasierravista.org, or visit our website riobravofmrp.org/qweek. This podcast was created with educational purposes only. Visit your primary care physician for additional medical advice. Our podcast team is Hector Arreaza, Alyssa Der Mugrdechian, Alejandro Gonzalez, Steven Saito, Valerie Civelli, Gina Cha, and Ariana Lundquist. Audio edition: Suraj Amrutia. See you soon!_____________________References:University of Southern California - Health Sciences. (2020, July 13). Significantly less addictive opioid may slow progression of osteoarthritis while easing pain. ScienceDaily. Retrieved August 12, 2020 from www.sciencedaily.com/releases/2020/07/200713120014.htm“Russia registers COVID-19 vaccine, Putin says daughter already inoculated” by Yaron Steinbuch. August 11, 2020, New York Post.Sterns, Richard H, “Causes of hypotonic hyponatremia in adults”, Up to Date, retrieved on Aug 13, 2020. https://www.uptodate.com/contents/causes-of-hypotonic-hyponatremia-in-adults?search=potomania&source=search_result&selectedTitle=2~2&usage_type=default&display_rank=2

No episódio 43, o Dr. Julio Marchini e o Dr. Patrick Áureo, médico assistente do PSM-HCFMUSP, discutem sobre anticoagulantes. Nesta parte 1 nos concentramos em explicar quais anticoagulantes existem, seu mecanismo de ação e como avaliar o sangramento que pode acometer pacientes usando anticoagulantes. Este podcast é patrocinado pelo Curso de Medicina de Emergência. Conheça mais no link www.emergenciausp.com.br/curso Meia-vida dos novos anticoagulantes Dabigatran - 12 a 17 horas; cinco meias-vidas: 2,5 e 3,5 dias. Rivaroxaban - 5 a 9 horas; cinco meias-vidas: 1 a 2 dias. Apixaban - 8 a 15 horas; cinco meias-vidas: 1,5 a 3 dias. Edoxaban - 6 a 11 horas; cinco meias-vidas: 1,3 a 2 dias. Betrixaban - 19 a 27 horas; cinco meias-vidas: 4 a 5,5 dias. Excreção renal dos novos anticoagulantes Dabigatran - A excreção é aproximadamente 80 a 85% renal. Rivaroxaban - a excreção é aproximadamente 35% renal; insuficiência hepática grave pode resultar em bioacumulação. Apixaban - a excreção é aproximadamente 25% renal; insuficiência hepática grave pode resultar em bioacumulação. Edoxaban - a excreção é aproximadamente 35% renal; insuficiência hepática grave pode resultar em bioacumulação. Betrixaban - A excreção é aproximadamente 11% renal, não recomendada na insuficiência hepática. Fonte: Uptodate, 2020 Se você gosta do nosso podcast, por favor nos avalie onde você escutou – seja no iTunes, Spotify, Stitcher ou outro. Mande feedback para 15minutos.emergencia@gmail.com. Siga-nos nas redes sociais: Dr. Patrick Aureo está no instagram (@patrickaureo) Dr. Julio Marchini está no Instagram (@dr.juliomarchini).

An interview with Dr. Anna Falanga on "Venous Thromboembolism Prophylaxis and Treatment in Patients with Cancer: ASCO Clinical Practice Guideline Update." The guideline revises several previous recommendations. Most notably, direct oral anticoagulants (DOACs) have been added as options for VTE prophylaxis and treatment. Read the full guideline at www.asco.org/supportive-care-guidelines Find all of ASCO's podcasts at podcast.asco.org  TRANSCRIPT Hi, my name is Clifford Hudis and I am the CEO of ASCO and the host of the ASCO in Action Podcast. About twice a month, I interview thought leaders in health care and experts in oncology, and we provide analysis and commentary on a wide range of cancer policy and practice issues.   You can find the ASCO in Action Podcast on Apple Podcasts or wherever you are listening to this show, and you can find all 9 of ASCO’s podcasts which cover a wide range of educational and scientific content and offer enriching insight into the world of cancer care at podcast.asco.org Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin. And today I'm interviewing Dr. Anna Falanga from the hospital Papa Giovanni XXIII in Bergamo, Italy. Senior author on "Venous Thromboembolism Prophylaxis and Treatment in Patients with Cancer: ASCO Clinical Practice Guidelines Update." Thank you for being here today, Dr. Falanga. Yes, thank you. I am very happy to talk on the update of the ASCO VTE guidelines. So this guideline was first published in 2007 with an update in 2013 and a reaffirmation in 2015. So what prompted this 2019 update? Thanks for this first question. I think that an update was urgently needed at this time. You know, before, the ASCO guidelines were published in 2007. And then an update was made in 2013, and the second one in 2015. But in 2015 was basically a confirmation of the previous 2013 update. Now the update was urgently needed, because in the very recent years there has been even more evidence of the relevance and impact of a venous thromboembolism in the cancer patients. But in addition, and very importantly, new data from prospective randomized clinical trials with the new drugs for the management of VT in the oncological patients have become available. In particular, as you know, low molecular weight heparins were largely used in the setting of the treatment and trauma prophylaxis in the cancer patients. And actually, the low molecular weight tapering have been the standard of treatment for many years. However, recently the results of prospective randomized clinical trials of direct oral anticoagulant, particularly, the anti-Xa inhibitors, Edoxaban and Rivaroxaban, for cancer associated with [INAUDIBLE] treatment support the role of this new oral agent in the VT management in this setting. And this is related to new politics in the VT management in these patients. So what are the key recommendations for this guideline update? The main changes to the previous recommendations are first that Rivaroxaban and Edoxiban, the two anti-Xa inhibitors oral anticoagulants have been added as an option for routine treatment in cancer patients in this update. Also, now we may offer thrombo prophylaxis with Apixaban, Rivaroxaban, or low molecular weight tapering to selected high-risk outpatients with cancer. And about other changes of these new guidelines compared to the last one include that patients with brain metastases have been addressed in the VT type treatment sections, whereas before, only patients with the primary tumors were mentioned in the previous edition. And finally, the recommendation regarding long-term postoperative thromboprophylaxis with low molecular weight heparin expanded to patients undergoing a major open or laparoscopic abdominal or pelvic surgery. These are the main changes that all I think are very, very important. Why is this guideline so important? And how does it affect practice? Well, I think that the question how these changes affect our practice is a very important question, because I believe that these guidelines reflect the new evidence that we have from the new data. And this data clearly expand our possibility to choose now between the different treatment options in the single patient in the cancer population. For instance, the new data show that treatment with [INAUDIBLE] anticoagulants compared to low molecular weight heparin lower the risk of a recurrent thrombosis. But in some instances there's a higher risk of bleeding, particularly in the gastrointestinal and urinary tract cancer patients. So therefore it is evident that the patient selection and the individualization of a therapy based on the patient characteristics and the type of cancer-- all these become very important. And we have the possibility now to choose between different treatments, or in the same patients we can change from one treatment to the other according to the face of the disease or complications if the patient is in a phase that is assuming chemotherapy with many side effects like nausea and vomiting. Of course, in these cases a parenteral injection is preferable for the management of a venous thromboembolism. Whereas in other instances, a long-term and oral intake is surely more convenient. So it depends also from the level of risk. But now for the six months treatment we can offer different choice of the oral treatment and also for high-risk patients the primary prophylaxis with Apixaban Rivaroxoaban, and a low molecular weight tapering can be chosen. And what should patients be aware of when it comes to VTE risks and treatments? I think that patients should be educated about the risk of a cancer associated with VTE. You know, there is that evidence that they are educated about it. And they know a lot better about neutropenia, and the fever associated with this the neutropenic condition and the other side effect. But they know very little about the possibility that they can experience venous thromboembolism.  So I think they should be taught on how to recognize the symptoms and alert their physician. You know, sometimes the symptoms are indistinguishable It can be just a little pain in the calf. And patients must know that these are to be considered important. They must alert their physician to undergo some test-- objective test-- to see if there is a real thrombosis in the leg or not. This is extremely important, because one important consequence of venous thromboembolism of the extremities is a pulmonary embolism that can be also fatal. So they must know about that. Also, I think they should know about the risk of bleeding associated with the anticoagulant treatment, and also that this risk of bleeding can be different in the different type of tumors. Finally, I think that also they must be told about the once they have, for instance, and episode of venous thromboembolism they have to receive a treatment for that, and these are usually six months to the minimum, and then we'll decide. So they must know what these are the efficacy and the safety profiles of the different drugs. They must know the differences in the route of administration and the other characteristics of the drug. So I think that their shared decision with the patients of the type of treatment must be an integral part of the decision making and is certainly desirable. Great. It sounds as though there's some important considerations for patients and important conversations which may be prompted by this guideline. So thank you for taking your time to discuss this with me today, Dr. Falanga. I thank you very much for this interview and talk that our colleagues and also the patients will be happy with these new guidelines of ASCO. Thank you. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full guideline, go to www.asco.org/supportive-care-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

An interview with Dr. Anna Falanga on "Venous Thromboembolism Prophylaxis and Treatment in Patients with Cancer: ASCO Clinical Practice Guideline Update." The guideline revises several previous recommendations. Most notably, direct oral anticoagulants (DOACs) have been added as options for VTE prophylaxis and treatment. Read the full guideline at www.asco.org/supportive-care-guidelines Find all of ASCO's podcasts at podcast.asco.org  TRANSCRIPT Hi, my name is Clifford Hudis and I am the CEO of ASCO and the host of the ASCO in Action Podcast. About twice a month, I interview thought leaders in health care and experts in oncology, and we provide analysis and commentary on a wide range of cancer policy and practice issues.   You can find the ASCO in Action Podcast on Apple Podcasts or wherever you are listening to this show, and you can find all 9 of ASCO’s podcasts which cover a wide range of educational and scientific content and offer enriching insight into the world of cancer care at podcast.asco.org Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin. And today I'm interviewing Dr. Anna Falanga from the hospital Papa Giovanni XXIII in Bergamo, Italy. Senior author on "Venous Thromboembolism Prophylaxis and Treatment in Patients with Cancer: ASCO Clinical Practice Guidelines Update." Thank you for being here today, Dr. Falanga. Yes, thank you. I am very happy to talk on the update of the ASCO VTE guidelines. So this guideline was first published in 2007 with an update in 2013 and a reaffirmation in 2015. So what prompted this 2019 update? Thanks for this first question. I think that an update was urgently needed at this time. You know, before, the ASCO guidelines were published in 2007. And then an update was made in 2013, and the second one in 2015. But in 2015 was basically a confirmation of the previous 2013 update. Now the update was urgently needed, because in the very recent years there has been even more evidence of the relevance and impact of a venous thromboembolism in the cancer patients. But in addition, and very importantly, new data from prospective randomized clinical trials with the new drugs for the management of VT in the oncological patients have become available. In particular, as you know, low molecular weight heparins were largely used in the setting of the treatment and trauma prophylaxis in the cancer patients. And actually, the low molecular weight tapering have been the standard of treatment for many years. However, recently the results of prospective randomized clinical trials of direct oral anticoagulant, particularly, the anti-Xa inhibitors, Edoxaban and Rivaroxaban, for cancer associated with [INAUDIBLE] treatment support the role of this new oral agent in the VT management in this setting. And this is related to new politics in the VT management in these patients. So what are the key recommendations for this guideline update? The main changes to the previous recommendations are first that Rivaroxaban and Edoxiban, the two anti-Xa inhibitors oral anticoagulants have been added as an option for routine treatment in cancer patients in this update. Also, now we may offer thrombo prophylaxis with Apixaban, Rivaroxaban, or low molecular weight tapering to selected high-risk outpatients with cancer. And about other changes of these new guidelines compared to the last one include that patients with brain metastases have been addressed in the VT type treatment sections, whereas before, only patients with the primary tumors were mentioned in the previous edition. And finally, the recommendation regarding long-term postoperative thromboprophylaxis with low molecular weight heparin expanded to patients undergoing a major open or laparoscopic abdominal or pelvic surgery. These are the main changes that all I think are very, very important. Why is this guideline so important? And how does it affect practice? Well, I think that the question how these changes affect our practice is a very important question, because I believe that these guidelines reflect the new evidence that we have from the new data. And this data clearly expand our possibility to choose now between the different treatment options in the single patient in the cancer population. For instance, the new data show that treatment with [INAUDIBLE] anticoagulants compared to low molecular weight heparin lower the risk of a recurrent thrombosis. But in some instances there's a higher risk of bleeding, particularly in the gastrointestinal and urinary tract cancer patients. So therefore it is evident that the patient selection and the individualization of a therapy based on the patient characteristics and the type of cancer-- all these become very important. And we have the possibility now to choose between different treatments, or in the same patients we can change from one treatment to the other according to the face of the disease or complications if the patient is in a phase that is assuming chemotherapy with many side effects like nausea and vomiting. Of course, in these cases a parenteral injection is preferable for the management of a venous thromboembolism. Whereas in other instances, a long-term and oral intake is surely more convenient. So it depends also from the level of risk. But now for the six months treatment we can offer different choice of the oral treatment and also for high-risk patients the primary prophylaxis with Apixaban Rivaroxoaban, and a low molecular weight tapering can be chosen. And what should patients be aware of when it comes to VTE risks and treatments? I think that patients should be educated about the risk of a cancer associated with VTE. You know, there is that evidence that they are educated about it. And they know a lot better about neutropenia, and the fever associated with this the neutropenic condition and the other side effect. But they know very little about the possibility that they can experience venous thromboembolism. s So I think they should be taught on how to recognize the symptoms and alert their physician. You know, sometimes the symptoms are indistinguishable It can be just a little pain in the calf. And patients must know that these are to be considered important. They must alert their physician to undergo some test-- objective test-- to see if there is a real thrombosis in the leg or not. This is extremely important, because one important consequence of venous thromboembolism of the extremities is a pulmonary embolism that can be also fatal. So they must know about that. Also, I think they should know about the risk of bleeding associated with the anticoagulant treatment, and also that this risk of bleeding can be different in the different type of tumors. Finally, I think that also they must be told about the once they have, for instance, and episode of venous thromboembolism they have to receive a treatment for that, and these are usually six months to the minimum, and then we'll decide. So they must know what these are the efficacy and the safety profiles of the different drugs. They must know the differences in the route of administration and the other characteristics of the drug. So I think that their shared decision with the patients of the type of treatment must be an integral part of the decision making and is certainly desirable. Great. It sounds as though there's some important considerations for patients and important conversations which may be prompted by this guideline. So thank you for taking your time to discuss this with me today, Dr. Falanga. I thank you very much for this interview and talk that our colleagues and also the patients will be happy with these new guidelines of ASCO. Thank you. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full guideline, go to www.asco.org/supportive-care-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

Commentary by Dr. Valentin Fuster

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. This week's issue provides much long awaited healthcare resource utilization and cost implications in the MOMENTUM 3 randomized controlled trial of a magnetically levitated cardiac pump in advanced heart failure. All of this coming right up after these summaries.                                                 The first original paper this week provides important mammalian data on the acute effects of phosphodiesterase type 1 inhibition on the heart. Now phosphodiesterase type 1, or PDE1, is known to hydrolyze cyclic AMP and cyclic GMP in the heart. However, what's important to understand is that data from rodents may not be applicable to humans because rodents express mostly the cyclic GMP favoring PDE1A isoform, whereas human hearts predominantly express PDE1C isoform which has a balanced selectivity for cyclic AMP and cyclic GMP.                                                 In today's paper, first author Dr Hashimoto, corresponding author Dr Kass from Johns Hopkins University School of Medicine and colleagues, determined the acute effects of PDE1 inhibition on PDE1C expressing mammals, dogs and rabbits, in normal and failing hearts. They found that selective inhibition of PDE1 with ITI-214 induced positive inotropic, lusitropic, chronotropic, and arterial vasodilatory effects in dogs and rabbits. These effects occurred via cyclic AMP modulation and were observed in failing hearts. ITI-214 contractile increase was insensitive to beta adrenergic blockade or heart rate increase, but inhibited in vivo by adenosine receptor inhibition. Furthermore, isolated myocytes revealed differences between PDE1 and PDE3 inhibition. Wherein PDE3 inhibition, augmented beta receptor agonism and calcium transients, whereas PDE1 inhibition enhanced function without calcium increase. These findings have important clinical implications for ITI-214 which has completed phase 1 trials and may provide a novel therapy for heart failure.                                                 We know that macrophages are involved in foam cell formation in atherosclerotic plaques, but our next paper tells us we may now have a way to therapeutically modify this. Co-corresponding authors Dr Wei and Schober from Ludwig Maximilian's University Munich elucidated the role of microRNA generating enzyme Dicer in macrophage activation during atherosclerosis. They showed that Dicer deletion in macrophages accelerated atherosclerosis in mice, along with enhanced inflammatory response and increased lipid accumulation in lesional macrophages. In vitro, alternative activation was limited, whereas lipid filled foam cell formation was exacerbated in Dicer deficient macrophages due to impaired mitochondrial fatty acid oxidative metabolism. MicroRNA biogenesis promoted the degradation of fatty acids by mitochondrial respiration in macrophages, which in turn reduced intracellular lipid storage and limited atherosclerosis. Thus, reducing foam cell formation in atherosclerotic arteries by enhancing energy metabolism through microRNA mediated fatty acid oxidation may be a promising approach for the treatment of atherosclerosis.                                                 The next study evaluates how aortic stiffening relates to resting cerebral blood flow and cerebral vascular reactivity in older adults. First and corresponding author Dr Jefferson from Vanderbilt Memory and Alzheimer's Center and her colleagues studied participants free of clinical dementia, stroke, or heart failure, including 155 older adults with normal cognition and 115 mild cognitive impairment. They found that greater thoracic aortic stiffening quantified by cardiac magnetic resonance was associated with lower cerebral blood flow in cognitively normal older adults. Aortic stiffening was associated with reduced resting cerebral blood flow in the presence of preserved reactivity and associated vasodilatory capacity, particularly among participants without hypertension. ApoE4, a well-known genetic susceptibility risk factor for Alzheimer's disease, modified the results with stronger effects among carriers in the temporal lobes, where Alzheimer's disease pathology is known to first evolve. In summary, greater aortic stiffening related to lower regional cerebral blood flow and higher cerebral vascular reactivity in cognitively normal older adults, especially among individuals with increased genetic predisposition for Alzheimer's disease. Understanding the association between higher aortic stiffness and compromised brain health, including cerebral hemodynamics, may allow for earlier detection and targeted interventions to prevent or mitigate the onset of more serious cerebral vascular damage associated with greater aortic stiffening.                                                 Aortic valve replacement for aortic stenosis is usually timed according to the development of symptoms, but could the timing be too late once irreversible myocardial scar has developed? Co-first authors Drs Musa and Treibel, corresponding author Dr Greenwood from University of Leeds and their colleagues found that in patients with severe aortic stenosis, focal myocardial fibrosis determined by cardiac magnetic resonance imaging was present in over 50% of patients and was associated with a two-fold higher late mortality. Focal scar was independently associated with all cause and cardiovascular mortality, after both surgical and transcatheter aortic valve replacement. In severe aortic stenosis, late gadolinium enhancement appears to be a useful biomarker of left ventricular remodeling, and its presence is associated with worse long-term outcomes following aortic valve intervention. Thus, in severe aortic stenosis, late gadolinium enhancement may be a useful biomarker of left ventricular remodeling, and its presence may be associated with worse long-term outcomes following aortic valve intervention.                                                 The next study suggests that endogenous factor Xa activity may be irrelevant pharmacodynamic marker to guide Edoxaban dosing in future. First author Dr Yin, corresponding author Dr Giugliano from TIMI Study Group, Brigham and Women's Hospital in Boston, and their colleagues, describe the value of endogenous factor Xa activity as a pharmacodynamic marker, linking Edoxaban concentrations and clinical outcomes in the ENGAGE AF-TIMI 48 trial. They showed that the extent of inhibition of endogenous factor Xa activity was influenced by Edoxaban dosing and clinical characteristics, and was associated with both antithrombotic benefit and risk of bleeding. The implications are that this approach of linking endogenous factor Xa activity to clinical outcomes may be used to guide dose selection in future clinical trials, to monitor patients in certain clinical scenarios, or to define the doses of oral factor Xa inhibitors in patients who require precise anticoagulation therapy.                                                 The next paper describes a novel multi-protein complex that plays a critical role in regulating cardiomyocyte survival. First author Dr Zhang, corresponding author Dr Yan from University of Rochester School of Medicine and Dentistry and colleagues, showed that phosphodiesterase 1C is activated by transient receptor potential canonical channel-3 derived calcium, thereby antagonizing adenosine A2 receptor cyclic GMP signaling and promoting cardiomyocyte death or apoptosis. Targeting these molecules individually, or in combination, may represent a compelling therapeutic strategy for potentiating cardiomyocyte survival.                                                 The final paper demonstrates a molecular link between two well-recognized biomarkers of fibrosis, Galectin-3 and Osteopontin. First author Dr Shirakawa, corresponding author Dr Sano from Keio University School of Medicine and their colleagues, showed that Osteopontin was almost exclusively produced by Galectin-3 high CD206 positive macrophages, which specifically appear in the infarct myocardium after a myocardial infarct. The interleukin-10-STAT3 Galectin-3 axis was essential for Osteopontin producing reparative macrophage polarization after myocardial infarction, and these macrophages contributed to tissue repair by promoting fibrosis and clearance of apoptotic cells. These results therefore suggest that Galectin-3 may contribute to reparative fibrosis in the infarct myocardium by controlling Osteopontin levels. And that brings us to the end of this week's summaries, now for a feature discussion.                                                 Left ventricular assist devices have truly revolutionized our management of advanced heart failure. In fact, these devices have allowed us to keep patients not just as a bridge to transplantation, but as destination therapy. The devices get better and better but also more and more expensive, and the problem is, that places a lot of strain on our healthcare systems. A lot of us are crying out for information on the cost effectiveness of these newer devices, and guess what? We have answers this week with our featured paper.                                                 I am delighted to have with us the first and corresponding author Dr Mandeep Mehra from Brigham and Women's Hospital in Boston, Massachusetts, as well as our senior editor Dr Biykem Bozkurt from Baylor College of Medicine in Houston, Texas. Hello, Mandeep and Biykem! I am so pleased to be talking about a subject really close to all our hearts. Mandeep, could you start by maybe sketching out the actual issue, and maybe reminding our audience what's the difference between the different types of left ventricular assist systems that you compared. Dr Mandeep Mehra:       The era of left ventricular assist devices took a major therapeutic shift when we recognized that we could usher in continuous flow devices. These are devices that generate no peripheral pulse, they do not have systole and diastole. And these devices are small in profile, have very few moving parts, and there are several commercially available devices, two in the United States and up to three worldwide, that bear these characteristics.                                                 The HeartMate II device, which is a continuous flow device that flows blood in an axial format. The HeartWare, or HVAD device, which is a centrifugal flow pump, where the blood comes in and then is ejected at a 90 degree angle. The Jarvik 2000 pump that is still used in some areas, in many regions experimentally, and then the new kid on the block, the HeartMate 3 device, which is a centrifugal flow pump with some very unique technological characteristics. Dr Carolyn Lam:                Nice! And now drumroll, please tell us what you found in your brilliant study this week. Dr Mandeep Mehra:       First, I'd like to remind the audience that the MOMENTUM 3 trial which randomized patients to the HeartMate II versus the HeartMate 3 device, was called MOMENTUM 3 and was a two-year study. We presented the pivotal two year trials results in 366 randomized patients earlier this year in The New England Journal of Medicine, and this study showed that the HeartMate 3 was superior on the primary endpoint when compared to the HeartMate II. The primary endpoint was survival, free of a disabling stroke, or the need to replace the pump surgically for a pump malfunction. And much of that, Carolyn, was driven by the need for replacement of the pump because the HeartMate 3 pump has some unique features that reduce its proclivity for pump thrombosis.                                                 The HeartMate 3 pump is a frictionless pump. It's completely, magnetically, dynamically, born in the rotor. It has wider blood flow paths, so we don't see hemolysis with this pump. And this pump also has an artificial intrinsic pulse that has been created, that pulsates the pump in a 40 beats per minute configuration. So this was the primary trial result, and one of the lucky foresights that we had when we designed the trial was to embed, prospectively, economic analysis within this trial. We recognized that the cost effectiveness related issues and cost configurations with these devices would become very, very important as we scale into today's day and age of healthcare transformation. And the paper that is being presented in Circulation this week, really speaks to the health resource utilization and cost outcomes between the two devices.                                                 We found that the HeartMate 3 pump is actually a cost minimization device, and what that means, Carolyn, is that we have become very used to thinking of new technology as providing incremental costs. So we think that, "Oh, well, what incremental costs should society bear for the benefits as we allocate new technology?" And in this particular trial, what we found is that while the costs of the pump itself, the HeartMate II and the HeartMate 3, were kept the same, which means its operational implant costs were the same, pretty much. We found that the HeartMate 3 pump was associated with a reduction in healthcare resource utilization over two years and with a marked decrease in cost. And in fact, our estimate of cost reduction was in the range of about 65 thousand dollars less, compared to the HeartMate II, in favor of the HeartMate 3. Dr Carolyn Lam:                Wow, Mandeep, first of all, congratulations on these remarkable findings. Biykem, I really have to bring you in here. What do you think of the implications of this? Dr Biykem Bozkurt:         First, I would like to congratulate the authors for a very innovative approach. As Mandeep has stated, they prospectively collected very challenging billing data from the hospitals, and then also did a very complex analysis including the VRG, as well as looking at payer reimbursements for public versus private. And did a variety of subgroup analysis, which I thought was quite helpful in sorting out that perhaps the cost effectiveness was concurrent both from the Medicare, the public, as well as the private, or regardless of the intent for destination versus bridge to transplant.                                                 Probably the most important concept when you look at these close analysis is incremental cost effectiveness ratio, per quality of adjusted life year gained. Now, I do realize the current analysis doesn't allow us to infer the ICER benefit or the incremental cost effectiveness, which I think the investigators are planning to do with a thousand and more patients over a course of two years, which is going to be probably the more definitive. But as it currently stands, with what is provided by Dr Mehra and his colleagues is, we're probably reaching that sweet spot of what is construed as the cost effectiveness ratio of a cost.                                                 Let's say 100 thousand dollars over the course of a year, then I would like to ask Mandeep whether on the prediction will reach that threshold of less than 100 thousand dollars. Because the former studies, looking at the ICER ratios, or incremental cost effectiveness ratios for the DT destination therapies, usually we select somewhere around 200 thousand dollars. And I know that usually that is seen as a prohibited cost, and there was a discussion whether we would be able to reduce the cost by about half, either doing index admission and add subsequent hospitalizations. With the data Dr Mehra and his colleagues have shown, it looks like the re-hospitalization cost is about, approximately half, or reduced by 50%. Mandeep, any thoughts on that, on that sweet spot? Dr Mandeep Mehra:       Yeah. I think, Biykem, you have articulated this extraordinarily well. And for the audience, since it's worldwide, I'd like to place a few things in perspective on how to think of economic modeling. First of all, the point I would make is that this is the first prospectively collected data that we have in the field, and as you pointed out, it was very, very difficult to pull this data together and is still very complex. But let's just think about what ICER really is. It all starts with what we consider to be health utility.                                                 For example, Carolyn, Biykem, and me less so, would have a health utility of 1.0, 1.0 means a perfect health utility number. And I know, Carolyn, you and Biykem are absolutely perfect so you would be a 1.0, I probably am not a 1.0. But a patient with advanced heart failure has a health utility of about .4, so that's only 40% of what is perfect. And when we place ventricular assist devices, whether you place the HeartMate 3 or the HeartMate II, the health utility actually jumps up to about .7. So it's not perfect yet, but it moves all the way up there.                                                 The incremental cost effectiveness ratios of implanting a device over time are calculated based on this health utility benefit, compared to the population of advanced heart failure. And the best current estimates of the HeartMate II are that ICER is about 200 thousand dollars, per quality adjusted life years gained, and this has been done by creating what's known as Markov modeling. A lot of that, by the way, is conjecture, it's not real information. It is predicted information, so one has to take that data with a grain of salt.                                                 Here in this health resource analysis for MOMENTUM 3, we actually looked at actual data. There are some estimates used in this analysis as well, where we did not have accurate billing forms available, but we focused on those things where we had very clear knowledge of the cost of outcomes. For example, we did not look at the costs of outpatient follow-up care. We mainly looked at the cost differences of hospitalizations. And what we essentially found here is that just looking at hospitalizations and differences between the two devices, the cost differential, whether it's Medicare which is public [inaudible 00:20:14], or whether it's commercial. It ranges somewhere between 50 to 65 thousand dollars of difference between the two devices.                                                 Now, if you assume that the ICER for the HeartMate II is accurately at about 200 thousand, and you reduce that ICER by about 50 to 60 thousand, the ICER would naturally come into the range of what you would consider to be about 135 thousand to 150 thousand dollars per quality adjusted life years gained for the HeartMate 3, compared to an advanced heart failure population. Once we look at it from that perspective, as Biykem pointed out, we are getting closer and closer to the societal norms.                                                 At one time-point, society used to think of a quality adjusted life years gained cost of 50 thousand dollars as something that would be acceptable to society, and this was seemingly based on the threshold for what dialysis provides in benefit. And now, we recognize that we have to really expand that to somewhere around 100 thousand more logically, or between 100 and 150 thousand for some technologies. The important thing I would say to you is that, that is society dependent. So what the United States considers to be a reasonable ICER, say 100 to 130 thousand dollars per quality adjusted life years gained, may not be the same that Great Britain would look at, or Sweden would look at, or another country would look at. And each country actually creates their own economic value propositions, and this will have to be taken into account as we think about this data as well. Dr Carolyn Lam:                How cleverly and clearly articulated, thank you so much Mandeep. Just one last question for both you and Biykem, what do you think this implies for moving to less and less advanced heart failure with these left ventricular assist device systems? Biykem? Dr Biykem Bozkurt:         It's an ever-expanding field, and as these devices are becoming smaller, lower profile with lesser complications and more affordable, probably the utilization will likely increase as we have been seeing. As you know, even the percutaneous non-durable device used, as well as our mechanical circulatory support durable devices are definitely increasing utilization. And thus, one may wonder not only the bridge to transplantation, but the destination therapy portfolio, or bridge to decision portfolio, may really increase as these devices become safer and more affordable. Dr Carolyn Lam:                Wow, that's amazing. How about you, Mandeep, what do you think? Dr Mandeep Mehra:       Carolyn, I couldn't have said it any better than what Biykem articulated. I do think that at least in the United States, as we reach the thresholds of cost effectiveness that we as a society accept, we will start to see a lot more widespread utilization, particularly for lifelong therapy or so-called destination therapy. I completely agree with that. I think that moving the needle to the less sicker population is still challenging, because there are complications with these devices that make that slightly difficult.                                                 There was a trial called the REVIVE-IT trial that was stopped midstream largely because of concerns about pump thrombosis, and that trial was looking at taking these devices to a less sick NYHA class 3 population and was stopped midstream. Now that the HeartMate 3 has pretty much resolved the issue of pump thrombosis, and even show a halfing in stroke rates with this device over two years, I think that that portfolio of evidence needs to be reopened. I would caution though, that until we have confirmatory randomized data in those less sick populations, the use to that population should still stay restricted. Dr Carolyn Lam:                I don't think anyone could have said it better than both of you. Thank you so much for this very insightful and balanced conversation.                                                 Thank you so much for listening today. You were listening to Circulation on the Run, and don't forget to tune again next week.  

Commentary by Dr. Valentin Fuster

For the treatment of cancer-associated VTE, LMWHs are recommended over warfarin (Grade 2B) and DOACs (all Grade 2C).  Warfarin therapy in cancer-associated VTE is often made more difficult by wildly fluctuating international normalized ratios, procedure-related interruptions, as well as numerous drug-drug and drug-food interactions.  While DOACs have been widely used in the treatment of VTE, there is very little data supporting their use in patients with active cancer until now with the publication of the Hokusai VTE Cancer study. Guest Authors:  Elizabeth Scheffel, PharmD and Christa George, PharmD, BCPS, BCACP, CDE Music by Good Talk

Today’s UpToDate Talk episode features discussions related to three papers published in the New England Journal of Medicine. Dr. Jess Mandel discusses anticoagulation options for cancer-associated venous thromboembolism, and Dr. George Mallory discusses two studies of tezacaftor-ivacaftor in patients with cystic fibrosis. Segment two begins at 11:32. Dr. Helen Hollingsworth hosts.

This week on The Rounds Table we are covering two important articles: the first examining combination opioids versus non-opiods for acute pain, and the second examining the use of edoxaban to treat cancer-associated venous thromboembolism (VTE). Kieran Quinn and Paxton Bach break it down for listeners. Opioid addiction is arguably the biggest epidemic of our ... The post Choosing the Right Drug: Non-Opioids for Acute Pain & Edoxaban for Venous Thromboembolism appeared first on Healthy Debate.

This week on The Rounds Table we are covering two important articles: the first examining combination opioids versus non-opiods for acute pain, and the second examining the use of edoxaban to treat cancer-associated venous thromboembolism (VTE). Kieran Quinn and Paxton Bach break it down for listeners. Opioid addiction is arguably the biggest epidemic of our ...The post Choosing the Right Drug: Non-Opioids for Acute Pain & Edoxaban for Venous Thromboembolism appeared first on Healthy Debate.

ATLANTA— In patients with a variety of cancers oral therapy with edoxaban—a direct oral anticoagulant (DOAC)—was just as effective and safe in terms of the risks of recurrent venous thromboembolism (VTE) and bleeding as injections with the low molecular weight …GARY RASKOB Mono INTERVIEW Productdion MASTER

Commentary by Dr. Valentin Fuster

  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 Centre and Duke-National University of Singapore. In just a moment, we're going to be discussing new results of the pioneer trial, and the patient with atrial fibrillation who undergoes intracoronary stenting, a familiar conundrum. What's the role of NOACs? Is there still a role for full-dose triple therapy with warfarin? First, here's your summary of this week's journal. The first paper tells us about the clinical impact of left atrial appendage closure. Dr. Melduni and colleagues from the Mayo Clinic in Rochester, Minnesota, studied 9,792 patients undergoing bypass or valve surgery between 2000 and 2005. They used propensity score matching to estimate the association of left atrial appendage closure with early post-operative atrial fibrillation- defined as atrial fibrillation within 30 days of surgery- ischemic stroke, and mortality. They found that after adjustment for treatment allocation bias, left atrial appendage closure during routine cardiac surgery was significantly associated with an increased risk of early post-operative atrial fibrillation, and did not influence the risk of stroke or mortality. They therefore concluded that it remains uncertain whether prophylactic exclusion of the left atrial appendage is warranted for stroke prevention during non-atrial-fibrillation-related cardiac surgery. The next study provides pre-clinical evidence that genes on sex chromosomes may contribute to the sexual dimorphism of abdominal aortic aneurysms. That is, we well know that abdominal aortic aneurysm is a male-predominant disease. Now, in this paper, by first author Dr. Alsiraj, corresponding author Dr. Cassis and colleagues from the University of Kentucky, female LDL-receptor-deficient mice, with an XX or XY sex chromosome complement, were infused with angiotensin II for 28 days to induce abdominal aortic aneurysms. DNA microarrays were performed on the abdominal aortas, and to mimic the males, the female mice were administered a single dose of testosterone. They found that an XY sex chromosome complement, in phenotypic females, profoundly influenced aortic gene expression profiles and promoted abdominal aortic aneurysm severity. When XY females were exposed to testosterone, aneurysm rupture rates were striking. The mechanisms for augmented abdominal aortic aneurysm severity in XY females included increased inflammation, augmented matrix metalloproteinases, and oxidative stress. These results, therefore, demonstrate that genes on the sex chromosomes regulate aortic vascular biology and contribute to sexual dimorphism of aortic abdominal aneurysms. Sex chromosome genes may therefore serve as novel targets for sex-specific abdominal aortic aneurysm therapeutics. The next two studies shed light on the mechanism of action of PCSK9 monoclonal antibodies on lipoprotein metabolism. In the first study, Dr. Watts and colleagues from University of Western Australia carried out a two-by-two factorial trial, of high-dose atorvastatin versus evolocumab on stable isotope tracer kinetics in 81 healthy, normal lipidemic, non-obese men. They found that both atorvastatin and evolocumab independently accelerated the fractional catabolism of VLDL apoB, IDL apoB, and LDL apoB. On the other hand, evolocumab, but not atorvastatin, also decreased the production rate of IDL apoB and LDL apoB. The reduction of LDL apoB and LDL cholesterol was significantly greater with a combination versus either mono-therapy. In summary, they found that in healthy, normal lipidemic men, evolocumab decreased the concentration of atherogenic lipoproteins, particularly LDL, by accelerating their catabolism, and by reducing IDL and LDL production. The latter effects are incremental to statins. The second paper to deal with this topic comes from Dr. Ginsberg and colleagues from Columbia University in New York, who studied 18 participants, this time 10 of whom were women, who completed a placebo-controlled two-period study, receiving two doses of placebo followed by five doses of alirocumab. These authors found that alirocumab decreased LDL cholesterol and LDL apoB by increasing IDL and LDL apoB fractional clearance rates, and by decreasing LDL apoB production rates. These results were consistent with increases in LDL receptors available to clear IDL and LDL from the blood during PCSK9 inhibition. These two papers are discussed in a beautiful accompanying editorial by Dr. Chris Packard from University of Glasgow. In his editorial entitled "Unpacking and Understanding the Impact of PCSK9 Inhibitors on Apolipoprotein B Metabolism." Those were your highlights! Now for our feature discussion. Today we are going to be discussing one of the most common conundrums in all of cardiovascular medicine, and that is the care of patients with atrial fibrillation who also need percutaneous coronary intervention. Of course, both dual antiplatelet therapy and oral anticoagulation therapy would be indicated to reduce the risk of stent thrombosis and thromboembolism in atrial fibrillation, respectively. However, with the intensification of the anti-thrombotic regimen, there is the inevitable trade-off with more bleeding. Now, to discuss this, we have the first and corresponding author on a very novel study of the pioneer trial, and that is Dr. Michael Gibson, from Harvard Medical School and Beth Israel Deaconess Medical Center. We also have the editorialist for this very exciting paper, Dr. Deepak Bhatt from Brigham and Women's Hospital, and finally, we have Dr. Dharam Kumbhani, associate editor from UT Southwestern. Welcome, gentlemen! Dr Deepak Bhatt:           Thank you. Dr Michael Gibson:          Thanks. Dr Dharam Kumbhani:   Thank you. Dr Carolyn Lam:                So, Michael, could I start with you? This is a sub-study of the pioneer study. Could you tell us how this is different from the primary results, what were you looking for, and what you found? Dr Michael Gibson:          As you know, as [inaudible 00:07:40] said, we have a lot of bleeding with conventional triple therapy, and we used two regimens to try and reduce that bleeding. One was a reduced dose of rivaroxaban, 15 milligrams, plus thienopyridine. The other strategy was baby dose rivaroxaban, 2.5 milligrams twice a day, plus DAPT. What we found in the overall study was a significant reduction in bleeding- from, say, 26.7% down to 18% for riva plus DAPT- that's the baby dose plus DAPT- and down to 16.8% for the 15 milligrams of riva plus the thienopyridine. You'd have to treat about 11 to 12 patients to prevent one significant bleeding event. That's the mainstay. What we found in this very, very important sub-study is that that was associated with reduction in hospitalization. All-cause hospitalization was reduced, and cardiovascular hospitalization went down from 28.4% to about 20% for the two regimens. Bleeding with hospitalization went down, from 10.5% to about 6%. At the end of the day, you'd only have to treat 10 to 15 people to prevent one hospitalization, so from a health economic perspective, and from a patient viewpoint and hassle perspective, this was very important. Dr Carolyn Lam:                In fact, Michael, I would say from a clinician-cardiologist perspective, these results are really very applicable. In fact, I really like, in the accompanying editorial, what Deepak wrote, that it may be one of those rare occasions where a sub-study provides very clinically meaningful information compared to the primary study. Deepak, would you like to elaborate a little bit more about that? Dr Deepak Bhatt:             Sure. A really great point that you've raised. It wasn't, in fact, a sub-study we're talking about in Circulation. It was an analysis from the overall trial, looking at a different endpoint than the primary endpoint, the hospitalization, and the composite of hospitalization and mortality. I think that's a very important endpoint. If it were a heart failure trial, for example, that's the endpoint everyone would hone in on- mortality and hospitalization. The fact that that was significantly reduced, I think, is very clinically meaningful. Mike mentioned the economic implications, which for sure are there, by reducing hospitalizations and re-hospitalizations. The impact on cardiovascular hospitalizations- the reduction there- I find particularly remarkable. The reduction in bleeding, of course, is good, and in its own right has a great deal of value, but the additional reduction in cardiovascular hospitalizations, I think, is quite reassuring for those that are worried about the efficacy of the two experimental regimens that he and his colleagues studied. Sure, the trial's not powered in each individual sub-group for rare events like stroke, but the fact that CV hospitalizations are not increased, and in fact reduced, tells me that this is a winning strategy or strategies. Dr Carolyn Lam:                Right. Michael, another issue, though- this is open label, and I suppose one of the criticisms could be that there is a bias for clinicians managing patients on the traditional Vitamin K antagonist to maybe hospitalize patients more for some reason. What is your response to that? Dr Michael Gibson:          That is always the criticism of an open label trial, but again, the events were adjudicated, and for the heart events, that's done in a blinded fashion, so it's reassuring that there was a blinded assessment of the heart events. Dr Carolyn Lam:                True. How about comments on generalizability? I mean, what do you think? Trial setting, real world ... Dr Michael Gibson:          Yeah, I think that's one of the advantages. This was very much a real-world kind of study. It was truly done throughout the world. We had a very broad entry criteria. Anyone who was getting a stent put in- you didn't have to have ACS, although about half the patients did. The only real exclusive criteria was you couldn't have any bleeding or be profoundly anemic. You couldn't have a stroke or [TIA 00:11:58] in the past. Other than that, it made real-world practice in a lot of ways. Dr Dharam Kumbhani:   This is Dharam. If I may ask both the other people on the call, is ... Rivaroxaban is not FDA approved, in these doses, for use. I'm wondering if they might provide some comment, given the benefit that we see in this trial, overall, what their thoughts are and what the next steps might be. Dr Carolyn Lam:                Sure. Maybe Michael, then Deepak? Dr Michael Gibson:          Yeah, that's a good point. It is important to point out that you'd need to check the prescribing information in your country. In some countries- I think it's about 54 countries- the 2.5 milligram dose is available. It is approved for ACS, but is not approved for a-fib. Then, you have a dose of 20 milligrams that's approved worldwide for a-fib, but there are some countries- it's important to note, in some countries, 15 milligrams is the full dose that's approved- say, in Japan and Taiwan. There are Japanese studies showing that 15 milligrams was not only safer than warfarin, but more efficacious than warfarin in a trial like J-ROCKET. You're right, the 15 milligram dose is available in the US- it's approved for renal insufficiency, but at this time, it's not labelled for the ACS or stented patient. But again, physicians are at liberty to look at this data, which is the first real data that we have to guide decision-making in this setting, and they're at liberty to make their own choices. Dr Deepak Bhatt:             Yeah, I would agree with that assessment, and emphasize ... Like Mike said, it's an international audience for Circulation, so I would say, look in your own country, and in many parts of Europe, the 2.5 milligram rivaroxaban dose is available and approved for ACS, and could therefore be used for this purpose, though not strictly falling within the label indications. In the US, there's the 15. I think, if I just answer the previous question, the results are very generalizable, and for doctors that critique that point, I'd say, "Why didn't you enroll your patients in the trial?" There's the RE-DUAL as well, that's ongoing, with dabigatran, AUGUSTUS with apixaban, and I'm missing one that's also ongoing as well, I think, but there are four different trials that are out there. The Pioneer was the first to report ... Dr Carolyn Lam:                I think you're thinking of the Entrust AF-PCI with Edoxaban. Dr Deepak Bhatt:             The most recent one, yes. I forgot the acronym, there. If people are really thinking that the results don't apply to their patients, well, there are trials that are ongoing. Enroll your patients. But to say, "Oh, my patients, I'm not going to enroll them in the trial," and then say, "The results aren't generalizable," I always find that an odd thing. I think the results are very generalizable. The one word of caution I would say, though, is to make sure to renally dose, as was done in the trial. That is, there was a downward adjustment in dose from the 15 milligrams to the 10. In real life, we've seen in registries with NOAC use, whether it's rivaroxaban or any of the others, a lot of times, the renal function is not carefully monitored in those patients that are on the fringe in terms of their renal function, and that's the one situation NOACs can backfire, where the dose isn't corrected for their degree of renal dysfunction. Other than that one caveat, I think the results are quite generalizable. Dr Carolyn Lam:                Excellent comments. We should wrap up soon, but not before I want to ask Dharam. Thank you for managing this beautiful paper. What, to you, is the take-home message for clinicians out there? Dr Dharam Kumbhani:   Yeah, it was an absolute honor and delight to manage this, and I think the paper's great. The editorial's great. It's gotten a great response. I think the take-home message is that this is a very clinically relevant question, and a very clinically relevant trial, and it shows that the needle will be moving towards using non-VKA-based agents, especially in patients such as this, who have both a-fib and PCI. I think this is very exciting space, a very important space. This trial suggests that if you use the strategy rivaroxaban low dose, with or without a DAPT, that it is safer, both in terms of mortality and bleeding, compared with what is traditionally being used with warfarin plus DAPT. I think this was a very, very exciting trial. Dr Carolyn Lam:                Indeed, and congratulations to all three of you. Thank you so much for joining me on Circulation On The Run. Thank you, listeners, for joining us too, and don't forget to tune in next week.  

Commentary by Dr. Valentin Fuster

Long-term anti-thrombotic treatment of embolic stroke sounds like a tricky field to navigate. Aspirin is the drug of choice in the acute setting for most patients, but when cardioembolic stroke is suspected, aspirin is inferior to anticoagulation for preventing recurrent stroke. In the age of novel oral anticoagulants, why choose warfarin and risk drug interactions, dietary restrictions and bleeding risk? In this episode, we discuss the pros and cons of each of the major NOACs for secondary stroke prevention. Enjoy! BrainWaves podcasts and online content are intended for medical education only and should not be used to guide medical decision making in routine clinical practice. Any cases discussed in this episode are fictional and do not contain any patient health identifying information. REFERENCES 1. Connolly SJ, et al. Dabigatran versus warfarin in patients with atrial fibrillation. New Engl J Med 2009; 361:1139-1151. 2. Granger CB, et al. Apixaban versus warfarin in patients with atrial fibrillation. New Engl J Med 2011; 365:981-992. 3. Patel MR, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. New Engl J Med 2011; 365:883-891. 4. Giugliano RP, et al. Edoxaban versus warfarin in patients with atrial fibrillation. New Engl J Med 2013; 369:2093-2104.

Commentary by Dr. David Wilber

1) Guideline on prevention of stroke in nonvalvular atrial fibrillation. and 2) Topic of the month: Review of new oral anticoagulants for stroke. This podcast for the Neurology Journal begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the print issue of Neurology. In the second segment Dr. Brett Kissela interviews Dr. Gary Gronseth about AAN paper on prevention of stroke in nonvalvular atrial fibrillation. Dr. James Addington is reading our e-Pearl of the week about superficial siderosis. In the next part of the podcast Dr. Andy Southerland interviews Dr. Seemant Chaturvedi about Edoxaban, non-pharmaceutical options for stroke prevention in afib: ablation, atrial appendage occluder devices and any other options. The participants had nothing to disclose except Drs. Kissela, Gronseth, Addington, Southerland and Chaturvedi.Dr. Kissela serves on scientific advisory board for Allergan, Inc.; has received funding for travel and speaker honoraria from Allergan, Inc.; has received research support from the NIH, will receive compensation from Reata Pharmaceuticals, Inc. for serving on the Event Adjudication Committee for the BEACON study, which they are sponsoring and provides medico-legal reviews.Dr. Gronseth serves as Associate Editor for for Neurology®; serves on the editorial board of Neurology Now and receives research support from the American Academy of Neurology.Dr. Addington serves on the editorial team for the Neurology® Resident and Fellow Section. Dr. Southerland serves as Podcast Deputy Editor for Neurology®; serves as Clinical Research Advisor for Totier Technologies, Inc.Dr. Chaturvedi serves as an editorial board member for Neurology®, Stroke; serves as contributing editor NEJM Journal Watch Neurology; serves as executive committee member for ACT I study; is a consultant for Genetech, Inc., Boehringer Ingelheim, Abbott Vascular, Thorhill research, WL Gore, Bristol-Myers Squibb; receives research support from Daichi Sankyo, AstraZeneca, Pfizer Inc, NIH; received compensation for expert witness testimony.

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