Comparative effectiveness of GDMT in the prevention of HF morbidity and death among patients with HFrEF in a U.S. database

Abstract

Abstract Background The incremental benefit of comprehensive over conventional guideline-directed medical therapy (GDMT) in real-world setting has not been well demonstrated in patients with heart failure with reduced ejection fraction (HFrEF). This study aims to compare patients on GDMT, including first-line therapy from the most recent US guidelines on the prevention of worsening heart failure events (WHFE) and all-cause death. Methods This study used Optum’s de-identified Clinformatics® Data Mart Database to identify patients who have diagnosed HFrEF and prescription fills for components of GDMT ("Conventional GDMT" i.e., ACEi or ARB, and beta-blocker) and first-line therapy from the most recent US guidelines ("2022 GDMT:" i.e., ARNi, MRA, beta-blocker, SGLT2i) between Jan2020 and Mar2022. This study characterized patients on both types of GDMT and compared the residual risk of WHF events (HF hospitalizations or receipt of IV diuresis) and death. Results The Conventional and 2022 GDMT cohorts included 26,517 and 2,775 patients, respectively. The Conventional GDMT cohort was older (74 vs. 68 years), more often female (41% vs. 33%) and white (67% vs. 60%). In general, they had more comorbidities, but a smaller proportion had diabetes mellitus (53% vs. 67%) and PVD (37% vs. 58%). The unadjusted Kaplan Meier curves show time from GDMT initiation to WHFE, or all-cause death was significantly (p<0.01) faster in the Conventional GDMT cohort compared to 2022 GDMT cohort. The unadjusted HR for experiencing a WHFE or all-cause death after starting GDMT was 0.88 (p<0.01) and 0.48 (p<0.001), comparing the 2022 GDMT cohort to Conventional GDMT cohort. These results were attenuated (WHFE: HR: 0.90, p = 0.02; all-cause death: HR: 0.66, p<0.001) after adjusting for demographic characteristics and comorbidities. Conclusion In this sample, patients on the most recent GDMT (2022 GDMT cohort) had better outcomes than those on conventional GDMT. However, the improvement was less noticeable in the prevention of WHFE. Results highlight the ongoing risk of HF-related morbidity and all-cause mortality among patients with HFrEF, despite the use of first-line therapy and underscores the need for therapeutics beyond optimized GDMT to lower the risk in this high-risk population.