Welcome back to What’s it Worth! Join your hosts, Dr. Diana Langworthy and Dr. Garrison Avery (PGY1 Pharmacy Resident), as we discuss the STOP ACEi trial comparing continuation of ACEi/ARB (angiotensin converting enzyme inhibitors/angiotensin receptor blockers) therapy in ESKD vs discontinuation of ACEi/ARB therapy. The authors sought to answer the question - Does discontinuation vs continuation of ACEi/ARB therapy slow the decline in eGFR once someone progresses to Stage 4/5 CKD. Let's get into the weeds of baseline characteristics - follow the episode's breadcrumbs to see if you can spot the key unmeasured confounders in this publication!

Key Points

1. ACEi/ARB therapy has demonstrated proven benefit in slowing the progression of CKD when initiated in Stages 1-3
2. Robust evidence is lacking to guide continuation vs discontinuation of ACEi/ARB therapy once a patient progresses to Stage 4/5 CKD
3. Compound symmetry covariance structures can be a useful statistical tool when the change between study visits in the key measurements is not anticipated to vary greatly (confused? So were we! Listen in for an explanation.)
4. What baseline characteristics might impact the primary outcome that may not have been accounted for? ------> Tune in to find out!

References

1. [EPISODE TRIAL] Bhandari S, Mehta S, Khwaja A, et al. Renin-Angiotensin System Inhibition in Advanced Chronic Kidney Disease. The STOP ACEi Trial. NEJM 2022;387:2021-2032.

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. Delgado C, Baweja M, Crews, D, et al. A Unifying Approach for GFR Estimation: Recommendations of the NKF-ASN Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease. JASN 2021;32(1@):2994-3015

4. Xie X, Liu Y, Perkovic V, et al. Renin-Angiotensin System Inhibitors and Kidney and Cardiovascular Outcomes in Patients with CKD: A Bayesian Network Meta-analysis of Randomized Clinical Trials. AJKD 2016;67(5):728-741.

5. DynaMed. Chronic Kidney Disease (CKD) in Adults. EBSCO Information Services. Accessed May 19, 2025. https://www-dynamed-com.ezp3.lib.umn.edu/condition/chronic-kidney-disease-ckd-in-adults-1

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, PGY1 Pharmacy Resident

University of Minnesota Medical Center - East Bank

Episode 2 of the Double Header with the Minnesota Twins! The first article, the SEQUOIA trial, was discussed in the preceding episode with Mckay Carstens... did you guess correctly for which twin was speaking? He's passing the baton to his brother Kane to discuss management of portal hypertension in patients with cirrhosis. We're looking back in time with a retrospective study that investigated whether carvedilol showed more effectiveness compared with classical NSBBs to prevent decompensation in patients with cirrhosis. Stick with us to see if the weight of portal hypertension is lifted in this cohort and explore the role of selection bias in retrospective cohort studies.

Key Points

1. Cirrhosis is a leading cause of liver-related morbidity worldwide and managing complications like portal hypertension is key to improving outcomes
2. Progression to decompensated cirrhosis—marked by ascites, variceal bleeding, or encephalopathy—reduces median survival to approximately 2 years thus highlighting the importance of prevention of decompensating events.
3. Carvedilol has gained attention for its added alpha-1 blockade, offering greater portal pressure reduction—though its long-term benefits and safety compared to traditional NSBBs remain under investigation
4. Get curious about selection bias - can we confidently interpret and apply these trial results? ------> Tune in to find out!

References

1. [EPISODE TRIAL] Fortea JI, Alvarado-Tapias E, Simbrunner B, et al. Carvedilol vs. propranolol for the prevention of decompensation and mortality in patients with compensated and decompensated cirrhosis. Journal of Hepatology 2025; https://doi.org/10.1016/j.jhep.2024.12.017.

2. Kaplan DE, Ripoll C, Thiele M, et al. AASLD Practice Guidelines on risk stratification and management of portal hypertension and varices in cirrhosis. Hepatology 2024;79:1180-1211.
3. Turco L, Reiberger T, Vitale G, La Mura V. Carvedilol as the new non-selective beta-blocker of choice in patients with cirrhosis and portal hypertension. Liver International 2023;43(6):1183-1194.
4. Villanueva C, Torres F, Kumar Sarin S, et al. Carvedilol reduces the risk of decompensation and mortality in patients with compensated cirrhosis in a competing-risk meta-analysis. Journal of Hepatology 2022;77(4):1014-1025.
5. Austin PC, Stuart EA. Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies. Statistics in Medicine 2015;34(28);3661-3679.

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

Kane Carstens, PharmD

PGY1 Resident, University of Minnesota Medical Center East Bank

Mckay Carstens, PharmD

PGY1 Resident, University of Minnesota Medical Center East Bank

Join us for a Double Header with the Minnesota Twins! No, we haven't converted to a sports podcast... I have PGY1 Residents (who are identical twins), Kane and Mckay Carstens joining me for back-to-back journal critiques! The first article, the SEQUOIA trial, was conducted to determine the efficacy and safety of aficamten, a novel cardiac myosin inhibitor, in patients with obstructive Hypertrophic Cardiomyopathy (HoCM). Let's get into the weeds to see the forest for the trees - what is aficamten's possible place in therapy for HoCM?

Key Points

1. Hypertrophic Cardiomyopathy (HCM) is one of the most common genetic heart conditions worldwide
2. Historical pharmacologic treatments are aimed at symptom resolution, but there have not been agents that directly target the mechanism of disease
3. Cardiac myosin inhibitors are a new class of drugs on the block with promise for patients with HoCM
4. But what do hierarchical secondary outcomes tell us? ------> Tune in to find out!

References

1. [EPISODE TRIAL] Maron MS, Masri A, Nassif ME, et al. Aficamten for symptomatic obstructive hypertrophic cardiomyopathy [SEQUOIA-HCM]. NEJM 2024;390:1849-1861.

2. Maron BJ. Clinical course and management of hypertrophic cardiomyopathy. NEJM 2018.379:655-668.
3. Ommen SR, Ho CY, Asif IM, et al. 2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation 2024;149:e1239-e1311.
4. Laporte S, Divine M, Girault D, et al. What usage and what hierarchical order for secondary endpoints? Therapie 2016,71(1):35-41.

CPR Certification Links

American Heart Association CPR & First Aid: https://cpr.heart.org/en/course-catalog-search

HeartCert: https://heartcertcpr.com/

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

Kane Carstens, PharmD

PGY1 Resident, University of Minnesota Medical Center East Bank

Mckay Carstens, PharmD

PGY1 Resident, University of Minnesota Medical Center East Bank