Welcome back to What’s it Worth! Join your hosts, Dr. Diana Langworthy and P4 Garrison Avery, as we discuss the RENAL-AF trial comparing apixaban vs warfarin in hemodialysis patients. These authors aimed to assess safety and efficacy in one of the first prospective trials comparing DOACs with warfarin in hemodialysis patients. Ever read a trial that didn't enroll their goal number of patients? Let's dig into patient recruitment considerations in trials and also pragmatic applications to medication selection, and properties of drugs that can be cleared by hemodialysis with real pharmacokinetic data to support!

Key Points

1. The prevalence of atrial fibrillation in patients on hemodialysis has been noted to be as much as nine times higher than the general population
2. Warfarin presents a challenge as an anticoagulant in patients on hemodialysis due a heightened risk of bleeding and risk for vascular complications such as calciphylaxis
3. Studies that are published with neutral or negative findings can still provide important clinical context for understudied populations like patients on hemodialysis
4. What does this underpowered trial tell us? ------> Tune in to find out!

References

1. [EPISODE TRIAL] Pokorney SD, Chertow GM, Al-Khalidi HR, et al; RENAL-AF Investigators. Apixaban for Patients With Atrial Fibrillation on Hemodialysis: A Multicenter Randomized Controlled Trial. Circulation. 2022 Dec 6;146(23):1735-1745. doi: 10.1161/CIRCULATIONAHA.121.054990. Epub 2022 Nov 6. PMID: 36335914.

2. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2024 Apr;105(4S):S117-S314. doi: 10.1016/j.kint.2023.10.018. PMID: 38490803.

3. Joglar JA, Chung MK, Armbruster AL, et al. ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2024 Jan 2;149(1):e1-e156. doi: 10.1161/CIR.0000000000001193. Epub 2023 Nov 30. Erratum in: Circulation. 2024 Jan 2;149(1):e167. Erratum in: Circulation. 2024 Feb 27;149(9):e936. PMID: 38033089.

4. What's behind racial disparities in kidney disease? 2021. Harvard Health Publishing; Harvard Medical School. Accessed on March 10, 2024: https://www.health.harvard.edu/blog/whats-behind-racial-disparities-in-kidney-disease-2021020321842#:~:text=The%20most%20recent%20report%20from,per%20million%20for%20white%20Americans.
5. Mavrakanas TA, Samer CF, Nessim SJ, et al. Apixaban Pharmacokinetics at Steady State in Hemodialysis Patients. J Am Soc Nephrol. 2017 Jul;28(7):2241-2248. doi: 10.1681/ASN.2016090980. Epub 2017 Mar 16. PMID: 28302754; PMCID: PMC5491286.

6. Dialysis. National Kidney Foundation [Web]. 30 East 33rd Street, New York, NY 10016 © 2024 National Kidney Foundation Inc. Dialysis - Types, effectiveness, side effects | National Kidney Foundation

7. Vázquez, E., Vázquez-Sánchez, T. Sánchez-Perales, C. Letter by Vázquez et al Regarding Article, “Apixaban for Patients With Atrial Fibrillation on Hemodialysis: A Multicenter Randomized Controlled Trial” Circulation. 2023;148:378. DOI: 10.1161/CIRCULATIONAHA.122.063700 © 2023 American Heart Association, Inc.

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

Co-Host Information

Garrison (Griest) Avery, Student Pharmacist, Class of 2024

University of Minnesota College of Pharmacy

Welcome back to What’s it Worth! Join your hosts, Dr. Diana Langworthy and Garrison Avery, student PharmD, as we evaluate the 52 week reported outcomes of the ongoing Resmetirom Phase 3 trial. This trial is our first look at a medication currently seeking FDA approval to halt and reverse NASH and liver fibrosis. We also discuss Bonferroni statistical analysis, patients excluded from the trial, and bias in language.

Key Points

1. The FDA accelerated approval process might get your pharmacist-spidey senses going, but is it a concern?

2. Non-alcoholic steatohepatitis (NASH) is the most severe form of non-alcoholic fatty liver disease (NAFLD) and can progress to end stage liver disease if not managed properly

3. Recognizing when manuscript language may be suggestive of an effect (when one has not been statistically proven) is important to keep top of mind when critiquing an article.

4. Is there promise for patients with NAFLD to take their livers back in time? --> Tune in to find out!

References

1. [EPISODE TRIAL] Harrison SA, Bedossa P, Guy CD, et al; MAESTRO-NASH Investigators. A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis. N Engl J Med. 2024 Feb 8;390(6):497-509. doi: 10.1056/NEJMoa2309000. PMID: 38324483.
2. Kanwal F, Neuschwander-Tetri BA, Loomba R, Rinella ME. Metabolic dysfunction-associated steatotic liver disease: Update and impact of new nomenclature on the American Association for the Study of Liver Diseases practice fuidance on nonalcoholic fatty liver disease. Hepatology 2023;DOI: 10.1097/HEP.0000000000000670.
3. Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, et al. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease Hepatology 2023;77(5):1797-1835.
4. U.S. Food and Drug Administration. Accelerated Approval Program. Accessed March 8, 2024. https://www.fda.gov/drugs/nda-and-bla-approvals/accelerated-approval-program

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

Co-Host Information

Garrison (Griest) Avery, Student Pharmacist, Class of 2024

University of Minnesota College of Pharmacy

Did you miss us? We're back for Season 2 of What’s it Worth! Join your host, Dr. Diana Langworthy, and co-host Garrison (Griest) Avery (back at the end of his APPE year for some more EBP fun!), as they find out if phenobarbital is beating benzos in severe alcohol withdrawal! CI-WAt all the fuss is about in season two as we PAWSS and reflect on where single-site retrospective results and clinical takeaways can meet!

Key Points

1. Alcohol withdrawal syndrome is a complex process involving acute imbalances in excitatory and inhibitory neurotransmitters in the CNS that can predispose patients to potentially life threatening complications like seizure and alcohol withdrawal delirium.
2. Patients in vulnerable populations, like pregnant persons and imprisoned persons, represent a group that is often underrepresented in clinical trials - we discuss this from a retrospective and prospective angle.
3. The Poisson regression is used for analysis of count data while the Wilcoxan rank sum test is a nonparametric test that assumes unknown or not-normally distrubuted data.
4. Is phenobarbital back again for alcohol withdrawal syndrome? --> Tune in to find out!

References

1. [EPISODE TRIAL] D, Al-Hegelan M, Thompson J, Bronshteyn Y. Phenobarbital versus benzodiazepines in alcohol withdrawal syndrome. Neuropsychopharmacol Rep. 2023; 43: 532–541. https://doi.org/10.1002/npr2.12347
2. DiCenzo R. Clinical Pharmacist's Guide to Biostatistics and Literature Evaluation. ACCP. 2011. [Poisson and Wilcoxan information]
3. The ASAM Clinical Practice Guideline on Alcohol Withdrawal Management. American Society of Addiction Medicine, 2020. [Alcohol withdrawal management information, CIWA, PAWSS]
4. Weaver M, Jewell C, Tomlinson J. Phenobarbital for Treatment of Alcohol Withdrawal. Journal of Addictions Nursing 2009;20:1-5.

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

Co-Host Information

Garrison (Griest) Avery, Student Pharmacist, Class of 2024

University of Minnesota College of Pharmacy