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US nationwide estimates of the proportion of patients newly diagnosed with heart failure with reduced ejection fraction (HFrEF) eligible for quadruple medical therapy, and the associated benefits of rapid implementation, are not well characterized. This study sought to characterize the degree to which patients newly diagnosed with HFrEF are eligible for quadruple medical therapy, and the projected benefits of in-hospital initiation. Among patients hospitalized for newly diagnosed HFrEF in the Get With The Guidelines – Heart Failure registry from 2016-2023, eligibility criteria based on regulatory labeling, guidelines, and expert consensus documents were applied for ARNI, beta-blocker, MRA, and SGLT2i therapies. Of those eligible, the projected effect of quadruple therapy on 12-month mortality was modeled using treatment effects from pivotal clinical trials utilized by the ACC/AHA/HFSA heart failure guidelines, and compared with observed outcomes among patients treated with ACEI/ARB and beta-blockers. Of 33,036 patients newly diagnosed with HFrEF, 27,158 (82%) were eligible for quadruple therapy, and 30,613 (93%) were eligible for ≥3 components. From 2021-2023, of patients eligible for quadruple therapy, 15.3% were prescribed quadruple therapy and 41.5% were prescribed triple therapy. Among Medicare beneficiaries eligible for quadruple therapy, 12-month incidence of mortality was 24.7% and HF hospitalization was 22.2%. Applying the relative risk reductions in clinical trials, complete implementation of quadruple therapy by time of discharge was projected to yield absolute risk reductions in 12-month mortality of 10.4% (number-needed-to-treat NNT=10) compared with ACEI/ARB and beta-blocker, and 24.8% (NNT=4) compared with no GDMT. In this nationwide US cohort of patients hospitalized for newly diagnosed for HFrEF, more than 4 of 5 patients were projected as eligible for quadruple therapy at discharge, yet less than 1 in 6 were prescribed it. If clinical trial benefits can be fully realized, in-hospital initiation of quadruple medical therapy for newly diagnosed HFrEF would yield large absolute reductions in mortality.
Greene et al. (Mon,) studied this question.