The Latest on Heart Failure: Clinical Trials Summary

The Latest on Heart Failure: Clinical Trials Summary Posted By:
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Too often, we are faced with hectic workdays that lead into hectic home lives—when we clock out from work, we head back home to spending time with family, making dinners, running to sports events, not to mention taking care of the basic needs of daily living and making time for ourselves. So, who has time to read clinical trials in their spare time? How do we keep up with the massive amounts of data pouring out each month? It's difficult. This short article is intended to quickly summarize notable trials related to heart failure (HF); they are not meant to be comprehensive, but rather meant to give busy professionals a glimpse into the fast-paced clinical trial world regarding HF with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF).

TRED-HF trial: Therapy withdrawal in REcovered Dilated cardiomyopathy-Heart Failure. This trial investigated HF therapy withdrawal in patients with previous dilated cardiomyopathy and recovery of left ventricular (LV) function (defined as improvements in LV ejection fraction [LVEF] from <40% baseline to ≥50%, normalized LV end-diastolic volume, and N-terminal pro-B-type natriuretic peptide <250 ng/L).

Bottom line: Even after recovery from dilated cardiomyopathy, withdrawal of HF therapy often leads to relapse. Patients should likely be kept on guideline-directed medical therapy (GDMT) indefinitely.

RALES trial: Randomized Aldactone Evaluation Study. This trial, while older and less known than other studies, is noteworthy for consideration. It examined the effectiveness of aldosterone antagonists (namely spironolactone) in patients with severely reduced LVEF (≤35%).

Bottom line: The results of this trial showed that the use of aldosterone antagonists greatly reduces mortality and morbidity in patients with severe HF. Spironolactone should be considered in addition to GDMT.

TOPCAT trial: Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist. Spurred by previous positive results of spironolactone in the management of HFrEF, TOPCAT evaluated the use of spironolactone in patients with HFpEF.

Bottom line: There does not appear to be a cardiovascular (CV) benefit in using spironolactone in patients with HFpEF. Patients in TOPCAT treated with spironolactone had higher rates of hyperkalemia and renal failure than those treated with placebo, though it may reduce volume overload and lower blood pressure.

EMPEROR-Preserved trial: Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction. The name of the trial says it all—the previous EMPEROR trial tested the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin in patients with HFrEF, and in EMPEROR-Preserved the focus was directed to test its use in patients with HFpEF.

Bottom line: The results revealed empagliflozin provides benefit in reducing the combined risk of CV death and hospitalizations for HF in patients with HFpEF, regardless of the presence of diabetes.

PRESERVED-HF trial: Effects of Dapagliflozin on Biomarkers, Symptoms and Functional Status in Patients With PRESERVED Ejection Fraction Heart Failure. This study looked at the use of dapagliflozin in patients with HFpEF (median EF 60%) with specific regard to improvements of patient-reported symptoms based on Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS). Improvements in 6-minute walk test, KCCQ Overall Summary Score, and changes in weight and other key biomarkers were secondary endpoints.

Bottom line: The use of the SGLT2 inhibitor dapagliflozin showed an improvement in patient-reported symptoms in patients with HFpEF. The study population (N = 324) was notable for including 57% women and 30% African American participants.

DELIVER trial: Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure. This trial was designed to further examine the effects of the SGLT2 inhibitor dapagliflozin, plus conventional therapy, on CV death, hospitalization for HF, or urgent HF visits in patients with HF with mildly reduced and preserved LVEF (>40%) with or without diabetes.

Bottom line: This is the largest (N = 6263) and broadest trial of patients with HF with mildly reduced or preserved LVEF to date. Final results have not yet been published, though are expected in 2022.

References
  • Anker SD, et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021;385:1451.
  • Halliday BP, et al. Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy (TRED-HF): an open-label, pilot, randomised trial. Lancet. 2019;393:61.
  • Nassif J, et al. The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial. Nat Med. 2021;27:1954.
  • Pfeffer MA, et al. Regional variation in patients and outcomes in the treatment of preserved cardiac function heart failure with an aldosterone antagonist (TOPCAT) trial. Circulation. 2015;131:34.
  • Pitt B, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med.1999;341:709.
  • Solomon SD, et al. Baseline characteristics of patients with HF with mildly reduced and preserved ejection fraction: DELIVER trial. J Am Coll Cardiol HF. 2022;10:184.
  • Williams DM, Evans M. Dapagliflozin for heart failure with preserved ejection fraction: Will the DELIVER study deliver? Diabetes Ther. 2020;11:2207.

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