LAUSR

BACKGROUND The comparative effectiveness of differing doses of guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) on clinical and patient-reported outcomes in US clinical practice is unknown. This study sought to characterize associations between dosing of GDMT and outcomes for patients with HFrEF in U.S. clinical practice METHODS: : This analysis included 4,832 US outpatients with chronic HFrEF across 150 practices in the CHAMP-HF registry with no contraindication and available dosing data for at least 1 GDMT at baseline. Baseline dosing of angiotensin-converting enzyme (ACEI)/ angiotensin II receptor blocker (ARB)/ angiotensin receptor-neprilysin inhibitor (ARNI), beta-blocker, and mineralocorticoid receptor antagonist (MRA) therapies were examined. For each medication class, multivariable models assessed associations between medication dosing and clinical outcomes over 24 months (all-cause mortality, HF hospitalization) and patient-reported outcomes at 12 months (change in Kansas City Cardiomyopathy Questionnaire Overall Summary Score [KCCQ-OS]). RESULTS After adjustment, compared with target dosing, lower dosing was associated with higher all-cause mortality for ACEI/ARB/ARNI (50% to <100% target dose, HR 1.16 [95% CI 0.87-1.55]; <50% target dose, HR 1.37 [95% CI 1.05-1.79]; none, HR 1.75 [95% CI 1.32-2.34; overall p<0.001) and beta-blocker (50% to <100% target dose, HR 1.30 [95% CI 1.00-1.69]; <50% target dose, HR 1.41 [95% CI 1.11-1.79; none, HR 1.24 [95% CI 0.92-1.67]; overall p=0.042). Lower dosing of ACEI/ARB/ARNI was independently associated with higher risk of HF hospitalization (50% to <100% target dose, HR 1.08 [95% CI 0.90-1.30]; <50% target dose, HR 1.23 [1.04-1.47]; none, HR 1.29 [1.04-1.60]; overall p=0.046), but beta-blocker dosing was not (overall p=0.085). Target dosing of MRA was not associated with risk of mortality or HF hospitalization. For each GDMT, compared with target dosing, lower dosing was not associated with change in KCCQ-OS at 12 months, with potential exception of worsening KCCQ-OS with lower dosing of ACEI/ARB/ARNI. CONCLUSIONS In this contemporary US outpatient HFrEF registry, target dosing of ACEI/ARB/ARNI and beta-blocker therapy was associated with reduced mortality, and variably associated with HF hospitalization and patient-reported outcomes. MRA dosing was not associated with outcomes. The totality of these findings support the benefits of target dosing of GDMT in routine practice, as tolerated, with unmeasured differences between patients receiving differing dosages potentially explaining differing results seen here compared with randomized clinical trials.