What's it Worth? A Journal Club Podcast

Diana Langworthy
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Get into the weeds with us as we take deep dives into clinical trials and build the essential skills of evidence critique! This podcast is a tool for healthcare professions students and practitioners to sharpen their science sleuth skills, learn key concepts about study design, biostatistics, and application of evidence to clinical practice.

  1. 2 days ago

    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 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 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 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.  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.

    27 min

  2. 2 days ago

    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.

    7 min

  3. 19 Jun

    S4E6.5 - What's It Worth? For Everyone: Does Tylenol Cause Autism? What Studies Can and Can't Tell Us

    Welcome to What's It Worth? For Everyone — a shorter, everyone-friendly version of What's It Worth? focused on making health evidence clearer, calmer, and easier to use. In this episode, Dr. Diana Langworthy revisits the recent What's It Worth? long-form discussion with Dr. Tory Pressman and Dr. Alexis Quade about Tylenol — also known as acetaminophen or paracetamol — during pregnancy and concerns about autism, ADHD, and other neurodevelopmental disorders. The full episode breaks down a 2026 systematic review and meta-analysis in more detail. This companion episode pulls out the big-picture takeaways: what the study asked, why this question is hard to answer, what makes the evidence reassuring, and what we still cannot say with 100% certainty. If you've seen headlines about Tylenol and autism and wondered what to do with that information, this episode is designed to help you slow down the claim, understand the evidence, and ask better questions with your healthcare team. Key Points Tylenol, acetaminophen, and paracetamol refer to the same medication, which is commonly used during pregnancy for fever and pain. Questions about autism, ADHD, and neurodevelopmental disorders can feel deeply personal for parents and pregnant people, which is why clear and careful communication matters. The episode explains why observational studies can be tricky, especially when people take a medication because of fever, pain, infection, or another condition. We unpack the idea of confounding by indication — the possibility that the reason someone took the medication may also be part of the story. The 2026 systematic review and meta-analysis is reassuring because its stronger analyses, including sibling-comparison studies, did not show a meaningful association between prenatal acetaminophen exposure and autism, ADHD, or intellectual disability. The practical takeaway is not "take it whenever, however, forever," but rather: use medications thoughtfully, talk with your healthcare team, and do not let scary headlines become a source of blame. Questions Worth Asking What are the risks of not treating fever or pain during pregnancy? If I need acetaminophen, what dose and timing make sense for me? How often is too often to need it? Are there non-medication options that fit my symptoms? Is there anything about my pregnancy or health history that changes the risk-benefit balance? This episode is for informational and educational purposes only and is not intended to replace advice from a licensed healthcare professional. Host Information Diana Langworthy, PharmD, BCPS Associate Professor, University of Minnesota College of Pharmacy Clinical Pharmacist, Adult Inpatient Internal Medicine LinkedIn: Diana (Mack) Langworthy www.linkedin.com/in/diana-langworthy-4a765957 TikTok: Diana The Pharm.D.etective (@whatsitworthrx) References [Episode Study] D'Antonio F, Flacco ME, Della Valle L, Prasad S, Manzoli L, Samara A, Khalil A. Prenatal paracetamol exposure and child neurodevelopment: a systematic review and meta-analysis. Lancet Obstet Gynaecol Womens Health. Published online January 16, 2026. doi:10.1016/S3050-5038(25)00211-0 Prada D, Ritz B, Bauer AZ, Baccarelli AA. Evaluation of the evidence on acetaminophen use and neurodevelopmental disorders using the Navigation Guide methodology. Environmental Health. 2025;24:56. doi:10.1186/s12940-025-01208-0 American College of Obstetricians and Gynecologists. Acetaminophen Use in Pregnancy and Neurodevelopmental Outcomes. Practice Advisory. Published September 22, 2025. Accessed April 13, 2026. Bérard A, Cottin J, Leal LF, et al. Systematic Review and Meta-Analysis: Acetaminophen Use During Pregnancy and the Risk of Neurodevelopmental Disorders in Childhood. J Am Acad Child Adolesc Psychiatry. 2026;65(4):484-504. Sheikh J, Allotey J, Khashan AS, et al. Maternal paracetamol (acetaminophen) use during pregnancy and risk of autism and attention deficit/hyperactivity disorder in offspring: umbrella review of systematic reviews. BMJ. 2025;391:e088141. Lee PC, Chen CY, Pan ML, et al. Maternal Acetaminophen Use and Child Neurodevelopment. JAMA Pediatr. Published online March 9, 2026. doi:10.1001/jamapediatrics.2026.0071.

    12 min

  4. 16 Jun

    S4E6 - Tylenol and Neurodevelopmental Disorders: Reassurance from a 2026 Systematic Review

    Welcome back to What's it Worth! Join your host, Dr. Diana Langworthy, and guests Dr. Alexis Quade and Dr. Tory Pressman, as they break down a 2026 systematic review and meta-analysis evaluating prenatal paracetamol exposure and child neurodevelopmental outcomes, including autism spectrum disorder, attention-deficit/hyperactivity disorder (ADHD), and intellectual disability. After renewed public attention in 2025 around Tylenol use in pregnancy and neurodevelopmental disorders, clinicians and patients are left asking how much weight to give observational medication safety signals. This episode explores how study design, confounding, outcome definitions, and risk-benefit thinking shape what we can — and cannot — conclude from the evidence. Let's dive in and see what it's worth! Key Points We explore why Tylenol, pregnancy, autism, ADHD, and neurodevelopmental disorders became such a high-profile medication safety conversation. The episode critiques a 2026 systematic review and meta-analysis, with a focus on study design choices like sibling comparisons, adjusted observational data, validated outcomes, and risk-of-bias assessment. We discuss why confounding by indication matters when the exposure is a medication used for fever, pain, or illness during pregnancy. We contrast the 2026 systematic review with the 2025 Navigation Guide paper and ask whether environmental health methods can be directly applied to pregnancy medication safety questions. Drs. Quade and Pressman help translate the evidence into real-world counseling about uncertainty, risk, benefit, and trust. When headlines move faster than evidence, how should clinicians and patients decide what's actually worth changing? ------> Tune in to find out! References [Episode Study] D'Antonio F, Flacco ME, Della Valle L, Prasad S, Manzoli L, Samara A, Khalil A. Prenatal paracetamol exposure and child neurodevelopment: a systematic review and meta-analysis. Lancet Obstet Gynaecol Womens Health. Published online January 16, 2026. doi:10.1016/S3050-5038(25)00211-0 Prada D, Ritz B, Bauer AZ, Baccarelli AA. Evaluation of the evidence on acetaminophen use and neurodevelopmental disorders using the Navigation Guide methodology. Environmental Health. 2025;24:56. doi:10.1186/s12940-025-01208-0 American College of Obstetricians and Gynecologists. Acetaminophen Use in Pregnancy and Neurodevelopmental Outcomes. Practice Advisory. Published September 22, 2025. Accessed April 13, 2026. Bérard A, Cottin J, Leal LF, et al. Systematic Review and Meta-Analysis: Acetaminophen Use During Pregnancy and the Risk of Neurodevelopmental Disorders in Childhood. J Am Acad Child Adolesc Psychiatry. 2026;65(4):484-504. Sheikh J, Allotey J, Khashan AS, et al. Maternal paracetamol (acetaminophen) use during pregnancy and risk of autism and attention deficit/hyperactivity disorder in offspring: umbrella review of systematic reviews. BMJ. 2025;391:e088141. Lee PC, Chen CY, Pan ML, et al. Maternal Acetaminophen Use and Child Neurodevelopment. JAMA Pediatr. Published online March 9, 2026. doi:10.1001/jamapediatrics.2026.0071.

    47 min

  5. 27 May

    S4E5 - COBRRA Trial Breakdown: Bleeding Risk with Apixaban vs Rivaroxaban

    Welcome back to What's it Worth! Join your host, Dr. Diana Langworthy, and guest host Tim Haas, PharmD Candidate 2028, as they break down the COBRRA trial — a head-to-head comparison of apixaban vs. rivaroxaban for the treatment of acute venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE). For years, clinicians have debated whether one DOAC may carry a lower bleeding risk than another, despite both apixaban and rivaroxaban being widely used first-line therapies for acute VTE. Did the COBRRA trial finally give us a clearer answer? Let's dive in and see what it's worth! Key Points COBRRA was a randomized trial comparing apixaban vs. rivaroxaban in patients with acute symptomatic DVT and PE, with a primary focus on clinically relevant bleeding risk. The trial included a broad real-world VTE population, including patients with both provoked and unprovoked thromboembolism, pulmonary embolism, and deep vein thrombosis. We break down the Kaplan-Meier curve for clinically relevant bleeding and discuss what the timing of events may tell us about differences between these DOAC regimens. The study used a prospective randomized open-label blinded endpoint (PROBE) design, giving us an opportunity to discuss pragmatic trial methodology and real-world applicability. Which patients with acute VTE might benefit most from apixaban over rivaroxaban from a bleeding risk perspective? ------> Tune in to find out! References [Episode Trial] Castellucci LA, Chen VM, Kovacs MJ, et al. Bleeding Risk with Apixaban vs. Rivaroxaban in Acute Venous Thromboembolism. N Engl J Med. 2026;394(11):1051-1060. doi:10.1056/NEJMoa2510703 Stevens SM, Woller SC, Kreuziger LB, et al. Antithrombotic Therapy for VTE Disease: Second Update of the CHEST Guideline and Expert Panel Report. Chest. 2021;160(6):e545-e608. 2026 AHA/ACC/ACCP/ACEP/CHEST/SCAI/SHM/SIR/SVM/SVN Guideline for the Evaluation and Management of Acute Pulmonary Embolism. Circulation. 2026. doi:10.1161/CIR.0000000000001415. Ortel TL, Neumann I, Ageno W, et al. American Society of Hematology 2020 Guidelines for Management of Venous Thromboembolism: Treatment of Deep Vein Thrombosis and Pulmonary Embolism. Blood Adv. 2020;4(19):4693-4738. Agnelli G, Buller HR, Cohen A, et al. Oral Apixaban for the Treatment of Acute Venous Thromboembolism. N Engl J Med. 2013;369:799-808. The EINSTEIN Investigators. Oral Rivaroxaban for Symptomatic Venous Thromboembolism. N Engl J Med. 2010;363:2499-2510. Beyer-Westendorf J, Lensing AWA, Arya R, et al. Choosing wisely: the impact of patient selection on efficacy and safety outcomes in the EINSTEIN-DVT/PE and AMPLIFY trials. Thromb Res. 2017;149:29-37.

    47 min

  6. 21 Apr

    S4E4 - Beyond Dopamine: Xanomeline-Trospium in Acute Schizophrenia

    Welcome back to What's it Worth! For over 70 years, the treatment of schizophrenia has been synonymous with dopamine D2 receptor blockade—until now. Join your host, Dr. Diana Langworthy, and guest Dr. Alexandra Rola (Psychiatry Clinical Pharmacist and Assistant Professor at Binghamton University) as they dive into the EMERGENT-3 trial. We're dissecting the efficacy and safety of xanomeline-trospium, a first-in-class muscarinic agonist that targets psychosis without the traditional side effects of dopamine antagonists. Is this the breakthrough psychiatry has been waiting for? Let's dive in and see what it's worth! Key Points Unlike traditional antipsychotics, xanomeline is a dual M1/M4-preferring muscarinic receptor agonist. By pairing it with trospium (a peripheral muscarinic antagonist), the "KarXT" combination aims to deliver CNS antipsychotic effects while minimizing peripheral side effects like nausea and vomiting. In this 5-week, Phase 3 trial of 256 adults with acute psychosis, xanomeline-trospium demonstrated a statistically significant and clinically meaningful 9.4-point greater reduction in the PANSS total score compared to placebo by week 5. The study showed significant improvements in both the Positive Syndrome Scale (hallucinations/delusions) and the Negative Syndrome Scale (social withdrawal/apathy), suggesting a more holistic impact on schizophrenia symptoms. While it avoids dopamine-related side effects, KarXT is associated with cholinergic-driven GI issues; nausea, dyspepsia, and vomiting were the most frequently reported adverse events. What are the ethics of a placebo controlled trial in acute psychosis when we have proven medications for treatment? Join us for an important conversation about equity and ethics in clinical trials. Can we treat psychosis without touching a single dopamine receptor? ------> Tune in to find out! References [EPISODE TRIAL] Kaul I, Sawchak S, Walling DP, et al. Efficacy and Safety of Xanomeline-Trospium Chloride in Schizophrenia: A Randomized Clinical Trial. JAMA Psychiatry. 2024;81(8):749-756. doi:10.1001/jamapsychiatry.2024.0785 World Medical Association. WMA Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Participants. Adopted by the 18th WMA General Assembly, Helsinki, Finland, June 1964, and amended by the 75th WMA General Assembly, Helsinki, Finland, October 2024. Waltz JA, Pujji SD, Colloca L. Placebo and nocebo phenomena in schizophrenia spectrum disorders: a narrative review on current knowledge and potential future directions. Psychol Med. 2025 Jul 18;55:e199. doi: 10.1017/S0033291725100901. Erratum in: Psychol Med. 2026 Feb 02;56:e37. doi: 10.1017/S0033291726103493.  Gara MA, Vega WA, Arndt S, et al. Influence of patient race and ethnicity on clinical assessment in patients with affective disorders. Arch Gen Psychiatry. 2012 Jun;69(6):593-600. doi: 10.1001/archgenpsychiatry.2011.2040.  Lawrence RE, Appelbaum PS. Ethics in placebo-controlled, acute treatment trials in schizophrenia: Two rival ethical frameworks. Schizophrenia Research 264 (2024) 372-377. Host Information Dr. Diana R. Langworthy, PharmD, BCPS Clinical Associate Professor, University of Minnesota College of Pharmacy Clinical Pharmacist - Inpatient Internal Medicine, M Health Fairview East Bank Hospital Guest Information Alexandra Rola, PharmD Clinical Assistant Professor, Pharmacy Practice, Binghamton University Psychiatry Clinical Pharmacist

    41 min

  7. 2 Apr

    S4E3 - The GLP-1 Battle: Cardiovascular outcomes of Tirzepatide vs. Dulaglutide in the SURPASS-CVOT Trial

    Welcome back to What's it Worth! In this episode, your host Dr. Diana Langworthy is joined by Mia Lussier, PharmD, MS, Clinical Assistant Professor at Binghamton University and ambulatory care specialist, to dissect the results of the SURPASS-CVOT trial . As the first large-scale trial directly comparing a dual GLP-1/GIP agonist to a proven GLP-1 receptor agonist for cardiovascular outcomes, we ask: is tirzepatide officially the champion of metabolic and cardiovascular health? Join us for an evidence detective session as we evaluate the clinical worth of these findings Key Points SURPASS-CVOT was an active-comparator, double-blind trial that randomized 13,299 patients with Type 2 Diabetes and established ASCVD to receive either tirzepatide (up to 15 mg) or dulaglutide (1.5 mg) once weekly . Tirzepatide met its primary end point of noninferiority to dulaglutide for MACE (cardiovascular death, MI, or stroke) with a hazard ratio of 0.92. However, it did not achieve statistically significant superiority for this composite outcome (P=0.09) While CV outcomes were noninferior, tirzepatide showed superior metabolic benefits, including a -1.66 percentage point reduction in A1c (vs. -0.88 with dulaglutide) and an 11.6% reduction in total body weight (vs. 4.8% with dulaglutide). In a pre-specified secondary analysis of high-risk CKD patients, tirzepatide significantly slowed the decline of eGFR compared to dulaglutide, showing a difference of 3.17 ml/min/1.73m² over 36 months. Both agents had similar overall adverse event rates Was dulaglutide 1.5 mg weekly the best comparator vs tirzepatide for cardiovascular outcomes? ---> Tune in to find out! References [EPISODE TRIAL] Nicholls SJ, Pavo I, Bhatt DL, et al. Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes. N Engl J Med. 2025;393(24):2409-2420. doi: 10.1056/NEJMoa2505928. Gerstein H, Colhoun H, Dagenais G et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. The Lancet, 2019; 394, 121-130. Pratley RE, Aroda VR, Lingvay I, et al. SUSTAIN 7 investigators. Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial. Lancet Diabetes Endocrinol. 2018 Apr;6(4):275-286. doi: 10.1016/S2213-8587(18)30024-X. Epub 2018 Feb 1. PMID: 29397376. Marson SP, Bain SC, Consoli A, et al.  Semaglutide and cardiovascular outcomes in patients with Type 2 Diabetes. N Engl J Med 2016;375:1834-1844. Join the Conversation Subscribe to the What's it Worth? Podcast on Substack If you want to get new episode alerts, bonus content, and continue reflecting on what studies like this mean for real clinicians and real patients—head over to the What's it Worth? substack.  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. Host Information Dr. Diana R. Langworthy, PharmD, BCPS Clinical Associate Professor, University of Minnesota College of Pharmacy Clinical Pharmacist - Inpatient Internal Medicine, M Health Fairview East Bank Hospital Guest Information Mia Lussier, PharmD, MS Clinical Assistant Professor, Pharmacy Practice, Binghamton University Ambulatory Care Specialist

    44 min

  8. 20 Mar

    S4E2 - The Kidney Formula Conundrum: Navigating eCrCl vs. eGFR in DOAC Dosing

    Welcome back to What's it Worth! Join your hosts, Dr. Diana Langworthy and guest Dr. Rachel Khan (Associate Professor at VCU School of Pharmacy), as they navigate the murky waters of renal function assessment in anticoagulant users. This episode dissects a critical insight from the ORBIT-AF II registry: the variability in DOAC (NOAC) dose eligibility when labs use newer kidney estimates . While clinical trials used Cockcroft-Gault (eCrCl), modern labs often report eGFR (MDRD or CKD-EPI), leading to a "renal identity crisis" for clinicians . We're putting on our EBP detective hats to explore why these formulas disagree—and what that means for your patients. Let's dive in and see what it's worth! Key Points The Gold Standard Gap: Landmark DOAC trials and product monographs almost exclusively use Cockcroft-Gault (eCrCl) for dosing, yet clinical labs have moved toward automated eGFR reporting . Formula Discordance: In the ORBIT-AF II cohort, agreement between eCrCl and eGFR was high overall (~93%), but declined in patients with established chronic kidney disease (CKD) . The "Misclassification" Mystery: Up to 42% of CKD patients could be classified for a different dose depending on which formula is used, with rivaroxaban showing the highest rates of variability . The Interpretive Challenge: While the study noted an association between formula-driven "undertreatment" and worse outcomes, we discuss the critical limitations—such as the lack of BSA-adjusted eGFR data—that make it difficult to conclude that eGFR is directly leading us to miss our target doses. Is your patient truly underdosed, or are we just using the wrong yardstick? ------> Tune in to find out! References [EPISODE TRIAL] Yao RJR, Holmes DN, Andrade JG, et al. Variability in Nonvitamin K Oral Anticoagulant Dose Eligibility and Adjustment According to Renal Formulae and Clinical Outcomes in Patients With Atrial Fibrillation With and Without Chronic Kidney Disease: Insights From ORBIT-AF II. J Am Heart As soc. 2023 Mar 21;12(6):e026605. doi: 10.1161/JAHA.122.026605.  St Peter WL, Bzowyckyj AS, Anderson-Haag T, et al; Moving forward from Cockcroft-Gault creatinine clearance to race-free estimated glomerular filtration rate to improve medication-related decision-making in adults across healthcare settings: A consensus of the National Kidney Foundation Workgroup for Implementation of Race-Free eGFR-Based Medication-Related Decisions. Am J Health Syst Pharm. 2025 Jun 11;82(12):644-659. Möller E, McIntosh JF, Van Slyke DD. STUDIES OF UREA EXCRETION. II: Relationship Between Urine Volume and the Rate of Urea Excretion by Normal Adults. J Clin Invest. 1928 Dec;6(3):427-65. doi: 10.1172/JCI100206. PMID: 16693839; PMCID: PMC434761. U.S. Food and Drug Administration (FDA). Pharmacokinetics in Patients with Impaired Renal Function — Study Design, Data Analysis, and Impact on Dosing and Labeling: Guidance for Industry. March 2024. Accessed December 2025.   Contact Information Podcast email: whatsitworthpodcast@gmail.com Host Information Dr. Diana R. Langworthy, PharmD, BCPS Clinical Associate Professor, University of Minnesota College of Pharmacy Clinical Pharmacist - Inpatient Internal Medicine, M Health Fairview East Bank Hospital Guest Information Dr. Rachel Khan, PharmD, BCPS Associate Professor, VCU School of Pharmacy Clinical Pharmacist - Internal Medicine, VCUHS

    52 min
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Get into the weeds with us as we take deep dives into clinical trials and build the essential skills of evidence critique! This podcast is a tool for healthcare professions students and practitioners to sharpen their science sleuth skills, learn key concepts about study design, biostatistics, and application of evidence to clinical practice.

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