Could a Low-Dose Diuretic Polypill Improve Outcomes in Heart Failure With Preserved Ejection Fraction?

Abstract

and nearly 1 million hospitalizations annually.2 HF with preserved ejection fraction (HFpEF) accounts for over 50% of all HF, and prevalence continues to increase given an aging population and rising prevalence of obesity and diabetes.3 Despite significant advances in the treatment of HF with reduced ejection fraction,4 disease-modifying therapies in HFpEF remain limited. Targeting congestion with loop and thiazide diuretic therapy remains the cornerstone of treatment,5,6 but emerging data on the benefits of adjunctive therapies, mineralocorticoid receptor antagonists (MRA), and sodium glucose co-transporter 2 inhibitors (SGLT2i), are promising with at least 14 ongoing studies examining these agents in HFpEF. However, gaps in uptake are likely to persist, if not grow, given challenges with clinical inertia, adherence, and increasing polypharmacy in patients with HFpEF. Herein, we describe the clinical need, summarize our rationale for, address potential arguments against, and provide a roadmap for a fixed lowdose combination therapy (or “polypill”) for HFpEF, incorporating loop diuretics, thiazide, or thiazide-like diuretics, MRA, and SGLT2i.