Two Impactful Heart Failure Trials

By Mark H. Drazner, M.D., M.Sc.

Professor of Internal Medicine
Clinical Chief of Cardiology

I congratulate the organizers of #AHA22 for another wonderful conference. I am particularly proud of the efforts of Amit Khera, M.D., M.Sc., this year’s Vice Chair of the Committee on Scientific Sessions Programming and point you to his contribution in this Physician Update for a “Behind the Scenes” look at the conference.

While there are many wonderful memories from #AHA22, I would like to highlight two trials from my field of heart failure.

1. Dealer’s Choice: Furosemide or Torsemide

Duke Health’s Robert Mentz, M.D., presented the primary results of TRANSFORM-HF, a comparative effectiveness trial that answered an age-old question: Does torsemide provide advantage as compared to furosemide? While many have advocated that torsemide, versus furosemide, would lead to improved clinical outcomes due to its higher bioavailability, that was not the result found: Mortality at approximately 18 months (primary endpoint) and all-cause hospitalization at 12 months (secondary endpoint) was the same in those who received either of the two loop diuretics.

TRANSFORM-HF stood out for being a streamlined and pragmatic comparative-effectiveness trial. Follow-up was per standard care with usual providers, and centralized phone interviews, rather than in-person study visits, were conducted. The successful completion of TRANSFORM-HF suggests this pragmatic strategy could be used to answer other important clinical questions, perhaps leaving a legacy even more important than its finding of comparable effectiveness between furosemide and torsemide.

2. Be STRONG in Decompensated Heart Failure

The most impactful trial at #AHA22 for me was STRONG-HF, an open-label, randomized trial of 1,078 participants with acute decompensated heart failure (ADHF) who were not on full doses of guideline-directed medical therapy (GDMT). Participants were randomized to usual versus high-intensity care. The latter was defined as implementation of a renin-angiotensin blocker (ACE-inhibitor, ARB, or ARNI), mineralocorticoid receptor antagonist (MRA), and beta blocker prior to discharge with uptitration to full doses by 2 weeks of discharge. Additionally, patients were followed closely with at least 4 (average of 5) clinic visits within 3 months of discharge. There was a significant increase in the implementation of GDMT in the high-intensity arm and a striking, absolute 8% reduction in the composite of death or heart failure readmission at 180 days (approximately 15% vs. 23%). There were more adverse events (most commonly low blood pressure, hyperkalemia, or renal insufficiency), but not serious adverse events, in the high-intensity group.

This trial was largely conducted before data were available showing benefit of SGLT2-inhibitors in patients with ADHF, so those agents were not part of the high-intensity intervention. Nevertheless, based on other rapidly accruing data, I suspect the results would have only been enhanced had SGLT2-inhibitors, the fourth member of the Fantastic Four, been included.

The STRONG-HF trial provides important data regarding how best to treat patients with acute decompensated heart failure. We need to ensure patients with ADHF are on GDMT prior to discharge, uptitrate GDMT without delay, and monitor our patients closely in the outpatient setting during this high-risk transition period. The burden is now on the medical community to implement this strategy to improve outcomes in the vulnerable population of patients with ADHF.

Email: mark.drazner@utsouthwestern.edu

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