Abstract 4365056: Vericiguat in acute coronary syndrome with reduced ejection fraction: the EVE-ACSrEF randomized controlled trial

Abstract

Background: Vericiguat has been approved in stable chronic heart failure with reduced ejection fraction (HFrEF). However, its efficacy in acute coronary syndrome (ACS) combined with left ventricular systolic dysfunction (left ventricular ejection fraction (LVEF) <45%) remains unclear. Hypothesis: In ACS patients with LVEF <45%, vericiguat combined with guideline-directed medical therapy (GDMT) can significantly reduce the risk of cardiovascular death or heart failure rehospitalization compared to GDMT alone. Methods: This single-center, prospective, randomized controlled trial enrolled 144 patients with ACS and LVEF <45%. Participants were randomly assigned in a 1:1 ratio to either vericiguat combined with GDMT group (target dose: 10 mg once daily) or GDMT alone for 12 months. The primary endpoint was the composite outcome of cardiovascular death or first hospitalization for heart failure. Secondary endpoints included dynamic changes in LVEF, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score (KCCQ-CSS), quality of life score (KCCQ-QoL), and total symptom score (KCCQ-TSS) during follow-up. Efficacy was assessed using intention-to-treat analysis. Results: During a median follow-up of 12 months, the primary outcome occurred in 4/72 (5.6%) patients in the vericiguat + GDMT group and 15/72 (20.8%) in the GDMT group (hazard ratio, 0.25; 95% confidence interval [CI], 0.08 to 0.75; P=0.008). For secondary endpoints, significant differences in NT-proBNP were observed between groups at 1 month (log-transformed mean difference [MD], 0.544; 95% CI,-0.97 to -0.12; P= 0.014) and persisted until study end (MD, 0.644; 95% CI,-1.11 to -0.58; P = 0.004). At 6 months, LVEF improved by 2.70% in the vericiguat + GDMT group compared to GDMT (95% CI, 1.56 to 4.45; P=0.030). No significant between-group difference was observed in the KCCQ-CCS (P=0.103).However, after 3 months, vericiguat + GDMT group demonstrated significant improvements in KCCQ-QoL（P=0.008) and KCCQ-TSS（P=0.020) compared with the GDMT group, with sustained benefits through subsequent follow-up. Conclusions: On the basis of GDMT, vericiguat significantly reduces cardiovascular death or heart failure rehospitalization risks and improves left ventricular systolic function and quality of life in ACS patients with LVEF <45%. (ClinicalTrials.gov number, NCT06321094).