What's it Worth? A Journal Club Podcast

S4E8 - Is it Possible to Decouple Bleeding from Clotting? Insights from the AZALEA-TIMI 71 Trial (Factor XI Series Part 2 of 2)

In Part 2 of our back-to-back series on the novel frontier of Factor XI inhibition, host Dr. Diana Langworthy and student co-hosts Caleb Nelson-Lange and Tim Haas dive into the AZALEA-TIMI 71 trial. Following our Part 1 discussion on the early termination of the OCEANIC-AF trial (asundexian), we turn our attention to abelacimab—a high-affinity, fully human monoclonal antibody that targets Factor XI. Unlike the small-molecule asundexian, abelacimab offers a unique pharmacokinetic profile with a once-monthly dosing potential. We explore safety outcomes of this novel agent. The team also tackles a crucial Pharmacy Detective Moment: Why did the study use rivaroxaban as the comparator instead of apixaban? We discuss how this choice impacts the "Worth" of the findings... Key Takeaways * Factor XI sits at the intersection of the intrinsic and common pathways. By inhibiting it, can we stop pathologic thrombosis while leaving "protective" hemostasis intact? * Abelacimab (both 90mg and 150mg) achieved a staggering reduction in the primary outcome compared to rivaroxaban —a composite of major and clinically relevant non-major bleeding—with hazard ratios of 0.33 and 0.26, respectively. * Why rivaroxaban? We dissect the strategic selection of a once-daily Xa inhibitor with a known higher GI bleeding profile and how it influences the trial's dramatic safety margin. * Was the early termination a win for patients or a loss for long-term efficacy data? ---> Tune in to find out! Featured Study Ruff, C. T., Patel, S. M., Giugliano, R. P., Morrow, D. A., Hug, B., Kuder, J. F., Goodrich, E. L., Chen, S. A., Goodman, S. G., Joung, B., Kiss, R. G., Spinar, J., Wojakowski, W., Weitz, J. I., Murphy, S. A., Wiviott, S. D., Parkar, S., Bloomfield, D., & Sabatine, M. S. (2024). Abelacimab versus rivaroxaban in patients with atrial fibrillation. New England Journal of Medicine, 391(1), 21-33. https://doi.org/10.1056/NEJMoa2406674 [https://doi.org/10.1056/NEJMoa2406674] Host Diana Langworthy, PharmD, BCPS | Associate Professor, University of Minnesota College of Pharmacy | Clinical Pharmacist, Inpatient Internal Medicine, M Health Fairview East Bank Hospital Student Co-Hosts Caleb Nelson-Lange | PharmD Candidate | Class of 2026 | University of Minnesota College of Pharmacy Tim Haas | PharmD Candidate | Class of 2028 | University of Minnesota College of Pharmacy Join the Conversation Have a study you'd like us to decode on a future episode? Email whatsitworthpodcast@gmail.com or share how you're navigating evidence in practice—I love hearing how clinicians and learners think through uncertainty. Or you can find me on my socials - Check out my Beacons for links to my TikTok and LinkedIn https://beacons.ai/diana.the.pharm.d.etective Additional References & Guidelines 1. Piccini, J. P., Patel, M. R., Steffel, J., et al. (2025). Asundexian versus apixaban in patients with atrial fibrillation. New England Journal of Medicine, 392(1), 23-32. https://doi.org/10.1056/NEJMoa2411777 [https://doi.org/10.1056/NEJMoa2411777] 2. Cohen, A. T., Hill, N. R., Luo, X., et al. (2024). A systematic review and network meta-analysis of the comparative safety of direct oral anticoagulants in patients with atrial fibrillation. Journal of Comparative Effectiveness Research, 13(2), 45-58. https://doi.org/10.2217/cer-2023-0182 [https://doi.org/10.2217/cer-2023-0182] 3. Joglar, J. A., Chung, M. K., Armbruster, A. L., et al. (2024). 2023 ACC/AHA/ACCP/HRS guideline for the diagnosis and management of patients with atrial fibrillation. Journal of the American College of Cardiology, 83(1), 109-279. https://doi.org/10.1016/j.jacc.2023.08.017 [https://doi.org/10.1016/j.jacc.2023.08.017]

S4E8.5 - What's it Worth? For Everyone. Are We Waiting Too Long for New Treatments?

In this What's It Worth? For Everyone episode, we're asking: Are we waiting too long for new treatments? If you've ever heard about a promising new medication, peptide, or breakthrough therapy and wondered, "If it works so well, why isn't everyone using it yet?"—you're not alone. It can feel frustrating to hear about exciting discoveries while waiting years before they become part of routine healthcare. In this episode, we take you behind the scenes of the scientific process to explore what happens between an exciting idea and a treatment that is recommended for patients. Along the way, we use recent blood thinner research as a real-world example of why asking the right questions—and taking the time to answer them—matters. Key Takeaways * A promising scientific idea is not the same as a proven treatment. * Clinical trials help researchers answer two critical questions: Does it work? and Is it safe? * Many exciting discoveries change as they are studied in larger groups of people. * The goal of the scientific process is not to slow innovation—it is to help ensure new treatments provide meaningful benefits while minimizing harm. * Progress in medicine depends on both curiosity and careful testing. Questions Worth Asking Use these questions to help guide conversations with your healthcare team when you hear about a new treatment: * How strong is the evidence supporting this treatment? * Has it been studied in people, or only in laboratory or animal studies? * What are the known benefits? * What are the known risks? * How does it compare with treatments that are already available? * Is this treatment appropriate for someone with my medical history? New discoveries are exciting—and they are how medicine moves forward. But every promising idea deserves careful testing before it becomes routine care. The goal isn't simply to bring new treatments to patients faster. It's to bring forward treatments that have been shown to make a meaningful difference in people's lives. This episode is for educational purposes only and is not medical advice. It does not replace care from your own healthcare team. 🎙️Host: Diana Langworthy, PharmD, BCPS | Associate Professor at the University of Minnesota College of Pharmacy | Clinical Pharmacist in Adult Internal Medicine, Fairview East Bank Hospital 📬 Enjoyed this episode? Find more evidence-based content, podcast episodes, social media, and ways to connect at https://beacons.ai/diana.the.pharm.d.etective [https://beacons.ai/diana.the.pharm.d.etective].

S4E8 - Why Efficacy Matters: Dissecting the Early Termination of Asundexian (Factor XI Series Part 1 of 2)

Welcome to Part 1 of our "What's it Worth?" deep dive into the next generation of anticoagulation. In this episode, host Dr. Diana Langworthy and student co-hosts Tim Haas and Caleb Nelson-Lange take on the OCEANIC-AF trial. This Phase 3, non-inferiority trial was designed to prove that the oral Factor XIa inhibitor, asundexian, could match the gold-standard apixaban in preventing stroke while significantly reducing bleeding. However, the trial took a dramatic turn when it was stopped early—not for safety, but for futility in efficacy . We unpack why asundexian failed to clear the non-inferiority hurdle and what this means for the "Factor XI hypothesis. In this episode, we move past the excitement of a "bleeding-free" anticoagulant to look at the clinical necessity of efficacy. We explore the challenge of going head-to-head with apixaban—widely considered the safest and most effective agent in our current toolkit—and discuss whether the "Factor XI hypothesis" was flawed or if the bar was simply set too high for this specific molecule. Key Takeaways * OCEANIC-AF was halted because asundexian was inferior to apixaban for preventing stroke and systemic embolism . * In this trial, asundexian went head-to-head with apixaban, the current market leader for safety and efficacy . * While asundexian showed numerical trends toward less bleeding, those gains were overshadowed by the increased risk of ischemic events compared to standard-of-care apixaban . * Is the Factor XI class dead on arrival, or was asundexian just the wrong molecule? ---> Tune in to find out! Episode Resources * Link to the Coagulation Cascade: https://www.bleeding.org/educational-programs/education/online-education/the-clotting-cascade [https://www.bleeding.org/educational-programs/education/online-education/the-clotting-cascade] Featured Study Piccini, J. P., Patel, M. R., Steffel, J., Ferdinand, K., Van Gelder, I. C., Russo, A. M., ... & OCEANIC-AF Steering Committee and Investigators. (2025). Asundexian versus apixaban in patients with atrial fibrillation. New England Journal of Medicine, 392(1), 23–32. https://doi.org/10.1056/NEJMoa2407105 [https://doi.org/10.1056/NEJMoa2407105] Host Diana Langworthy, PharmD, BCPS | Associate Professor, University of Minnesota College of Pharmacy | Clinical Pharmacist, Inpatient Internal Medicine, M Health Fairview East Bank Hospital Student Co-Hosts Caleb Nelson-Lange | PharmD Candidate | Class of 2026 | University of Minnesota College of Pharmacy Tim Haas | PharmD Candidate | Class of 2028 | University of Minnesota College of Pharmacy Join the Conversation Have a study you'd like us to decode on a future episode? Email whatsitworthpodcast@gmail.com or share how you're navigating evidence in practice—I love hearing how clinicians and learners think through uncertainty. Or you can find me on my socials - Check out my Beacons for links to my TikTok and LinkedIn https://beacons.ai/diana.the.pharm.d.etective Additional References & Guidelines 1. Joglar, J. A., Chung, M. K., Armbruster, A. L., et al. (2024). 2023 ACC/AHA/ACCP/HRS guideline for the diagnosis and management of patients with atrial fibrillation. Journal of the American College of Cardiology, 83(1), 109–279. https://doi.org/10.1016/j.jacc.2023.08.017 [https://doi.org/10.1016/j.jacc.2023.08.017] 2. Ruff, C. T., Patel, S. M., Giugliano, R. P., et al. (2024). Abelacimab versus rivaroxaban in patients with atrial fibrillation. New England Journal of Medicine, 391(1), 21–33. https://doi.org/10.1056/NEJMoa2406674 [https://doi.org/10.1056/NEJMoa2406674] 3. Piccini, J. P., Caso, V., Connolly, S. J., et al. (2022). Safety of the oral factor XIa inhibitor asundexian compared with apixaban in patients with atrial fibrillation (PACIFIC-AF): A multicentre, randomised, double-blind, double-dummy, dose-finding phase 2 study. The Lancet, 399(10333), 1383–1390.

S4E7.5 - What's it Worth? For Everyone. AFib, Blood Thinners, and Liver Disease: Questions to Ask Your Doctor

In this What's It Worth? For Everyone episode, we're talking about AFib, blood thinners, and liver disease. AFib stands for atrial fibrillation. It is a common heart rhythm problem that can increase the risk of stroke. Because of that stroke risk, many people with AFib are prescribed a blood thinner. But what if someone has AFib and also has liver disease or cirrhosis? That decision can be more complicated. In the full What's It Worth? episode, we discussed a systematic review and meta-analysis comparing DOACs with warfarin in people with atrial fibrillation and liver disease. DOACs are a group of blood thinners that include apixaban, also known as Eliquis, and rivaroxaban, also known as Xarelto. Key Takeaways * In this study, DOACs appeared to work similarly to warfarin for preventing stroke in people with AFib and liver disease. * DOACs also appeared to have a more favorable bleeding profile than warfarin in many patients, including patients with cirrhosis. * This episode explains why blood thinner decisions in liver disease are not one-size-fits-all. * We talk about how liver function, kidney function, bleeding history, clotting risk, and other medications can all affect which blood thinner may be the safest choice. * The core takeaway from the review is that DOACs may be reasonable options for many people with AFib and liver disease, but the decision still needs to be individualized. * Practical takeaway: Bring your full medication list to your appointment and ask your healthcare team how your liver disease, kidney function, age, weight, bleeding risk, and other medicines affect the blood thinner choice. Questions Worth Asking Use these questions to help guide a conversation with your healthcare team: * Why do I need a blood thinner? * What is my risk of stroke if I do not take one? * What is my personal risk of bleeding? * How severe is my liver disease? * Is this blood thinner safe for my level of liver function? * How is my kidney function? * Are any of my medicines raising my bleeding risk? * Are any of my medicines interacting with this blood thinner? * What bleeding symptoms should I watch for? * Who should I call if I notice bleeding or need a procedure? Bring your full medication list to your appointment. This includes prescription medicines, over-the-counter medicines, pain relievers like ibuprofen or naproxen, aspirin, vitamins, supplements, and medicines you only take once in a while. Having liver disease or cirrhosis does not automatically mean a person with AFib can never take a blood thinner. But it does mean the decision needs extra care. The goal is thoughtful, personalized care. This episode is for educational purposes only and is not medical advice. It does not replace care from your own healthcare team.

S4E7 - The Cirrhosis Paradox: Solving the DOAC vs. Warfarin Mystery in Liver Disease

For patients with atrial fibrillation and chronic liver disease, the "correct" anticoagulation strategy has long been a clinical catch-22. Balancing the high risk of stroke against the elevated risk of catastrophic bleeding—all while navigating a lack of randomized controlled trial (RCT) data—leaves clinicians in a difficult position. In this episode, host Dr. Diana Langworthy is joined by Dr. Erin Pauling (ambulatory care and cardiology specialist) and Caleb Nelson-Lange, PharmD (Class of 2026!) to decode a 2025 systematic review and meta-analysis. Together, they explore how DOACs perform against warfarin in this complex population and whether apixaban truly holds a safety edge. As evidence evolves, we must ask: Does the safety signal in observational data outweigh the lack of RCTs? Does the "worth" of DOACs hold up when the liver is failing? Key Points *]:pointer-events-auto R6Vx5W_threadScrollVars scroll-mb-[calc(var(--scroll-root-safe-area-inset-bottom,0px)+var(--thread-response-height))] scroll-mt-[calc(var(--header-height)+min(200px,max(70px,20svh)))]" dir="auto" data-turn-id= "request-WEB:cf4247c1-f811-45ea-a623-2c3768584f43-3" data-turn-id-container= "request-WEB:cf4247c1-f811-45ea-a623-2c3768584f43-3" data-testid= "conversation-turn-8" data-turn="assistant"> * This systematic review and meta-analysis evaluated DOACs versus VKAs in patients with atrial fibrillation and liver disease, including a cirrhosis subgroup. * Most included studies were observational, with limited randomized data. * Overall, DOACs appeared to have a favorable bleeding profile compared with VKAs, with similar stroke/systemic embolism outcomes. * Similar bleeding trends were seen in the cirrhosis subgroup. * We discuss why anticoagulation in liver disease requires individualized decision-making, including liver disease severity, bleeding history, clotting risk, and medication-specific considerations. * We also dig into the apixaban versus rivaroxaban subgroup findings and why they may differ between the broader liver disease population and the cirrhosis subgroup. * How should we interpret DOAC safety in liver disease and cirrhosis — and what do the agent-specific findings add? ---> Tune in to find out! Featured Study Zhou Q, Liu X, Liu S, Gu Z, Wu Y, Yang Y, Tao Y, Wei M. Effectiveness and safety of direct oral anticoagulants versus vitamin K antagonists in atrial fibrillation patients with liver disease: a systematic review and meta-analysis. Front Pharmacol. 2025 Jul 14;16:1620394. doi: 10.3389/fphar.2025.1620394. Host & Guest Information Diana Langworthy, PharmD, BCPS | Associate Professor, University of Minnesota College of Pharmacy Clinical Pharmacist | Inpatient Internal Medicine, M Health Fairview East Bank Hospital Erin Pauling, PharmD, BCACP, FAPhA | Clinical Associate Professor, Pharmacy Practice Binghamton University School of Pharmacy and Pharmaceutical Sciences | Ambulatory Care Pharmacist, United Health Services (UHS) Caleb Nelson-Lange PharmD | Class of 2026 | University of Minnesota College of Pharmacy Have a study you'd like us to decode on a future episode? Email whatsitworthpodcast@gmail.com or share how you're navigating evidence in practice—I love hearing how clinicians and learners think through uncertainty. Additional References 1. Joglar, J. A., Chung, M. K., Armbruster, A. L., et al. 2023 ACC/AHA/ACCP/HRS guideline for the diagnosis and management of patients with atrial fibrillation: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation, 2024 149(1), 109–279. https://doi.org/10.1016/j.jacc.2023.08.017 [https://doi.org/10.1016/j.jacc.2023.08.017] 2. Miranda, M., Sangos CKM, Barbosa GA, et al. Efficacy and safety of direct oral anticoagulants compared to vitamin K antagonists for atrial fibrillation in patients with liver cirrhosis: An updated systematic review and meta-analysis. J Clin Exper Hepatol 2025;15(4): https://doi.org/10.1016/j.jceh.2025.102534 3. Simon TG, Singer DE, Zhang Y, Mastrorilli JM, Cervone A, DiCesare E, Lin KJ. Comparative Effectiveness and Safety of Apixaban, Rivaroxaban, and Warfarin in Patients With Cirrhosis and Atrial Fibrillation : A Nationwide Cohort Study. Ann Intern Med. 2024 Aug;177(8):1028-1038. doi: 10.7326/M23-3067. 4. Yoo SY, Kim E, Nam GB, Lee D, Shim JH, Kim KM, Lim YS, Lee HC, Chung YH, Lee YS, Choi J. Safety of direct oral anticoagulants compared to warfarin in cirrhotic patients with atrial fibrillation. Korean J Intern Med. 2022 May;37(3):555-566. doi: 10.3904/kjim.2020.622.