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Eligibility for Quadruple Therapy in Newly Diagnosed HFrEF
Quick Takes
- Actual prescriptions for GDMT among patients hospitalized for new-onset HFrEF were remarkably low, with only 15.3% and 41.5% of patients prescribed quadruple and triple therapy, respectively.
- Applying the relative risk reductions in clinical trials suggests that complete implementation of quadruple therapy will yield absolute risk reductions in 12-month mortality of 10.4% (NNT = 10) compared with ACEi/ARB and beta-blocker, and 24.8% (NNT = 4) compared with no GDMT.
- These data suggest an unexploited opportunity for rapid in-hospital implementation of quadruple therapy, with such a strategy expected to substantially improve patient survival.
Study Questions:
What is the degree to which patients newly diagnosed with heart failure with reduced ejection fraction (HFrEF) are eligible for quadruple medical therapy, and what are the projected benefits of in-hospital initiation?
Methods:
The investigators applied eligibility criteria based on regulatory labeling, guidelines, and expert consensus documents among patients hospitalized for newly diagnosed HFrEF in the Get With The Guidelines–Heart Failure registry from 2016 to 2023, for angiotensin receptor-neprilysin inhibitor, beta-blocker, mineralocorticoid receptor antagonist, and sodium-glucose cotransporter-2 inhibitor 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 American Heart Association/American College of Cardiology/Heart Failure Society of America Guideline for the Management of Heart Failure, and compared with observed outcomes among patients treated with angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker (ACEi/ARB) and beta-blockers. The authors report the cumulative incidence and absolute risk difference between the curves reflecting the varying levels of guideline-directed medical therapy (GDMT).
Results:
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 to 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.
Conclusions:
The authors report that >4 of 5 patients hospitalized for newly diagnosed HFrEF were projected as eligible for quadruple therapy at discharge; yet, <1 in 6 were prescribed it.
Perspective:
This large contemporary cohort of patients hospitalized for new-onset HFrEF reports that actual prescriptions for GDMT were remarkably low, with only 15.3% and 41.5% of patients prescribed quadruple and triple therapy, respectively. Applying the relative risk reductions in clinical trials suggests that complete implementation of quadruple therapy by time of discharge will yield absolute risk reductions in 12-month mortality of 10.4% (NNT = 10) compared with ACEi/ARB and beta-blocker, and 24.8% (NNT = 4) compared with no GDMT. These data suggest an unexploited opportunity for rapid in-hospital implementation of quadruple therapy, with such a strategy expected to substantially improve patient survival. There appears to be an urgent need to optimize use of GDMT for newly diagnosed HFrEF and ensure that eligible patients have timely initiation of quadruple therapy at time of diagnosis, as tolerated.
Clinical Topics: Heart Failure and Cardiomyopathies
Keywords: Heart Failure, Reduced Ejection Fraction, Prescription Drugs
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