Vericiguat in patients with acute coronary syndrome and reduced ejection fraction: the EVE-ACSrEF study

Preclinical research has demonstrated that vericiguat can improve myocardial microcirculation. However, real-world evidence of using vericiguat alongside guideline-directed medical therapy (GDMT) in patients with acute coronary syndrome (ACS) complicated by heart failure with reduced ejection fraction (HFrEF) remains limited. In this prospective cohort study, 149 ACS patients with left ventricular ejection fraction (LVEF) below 45% were grouped by their treatment preference. Multivariable analyses were used to evaluate the effect of vericiguat on the composite endpoint of hospitalization for heart failure (HHF) or cardiovascular death (CVD). A linear mixed-effects model was used to analyze changes in LVEF and N-terminal pro-brain natriuretic peptide (NT-proBNP) from baseline to 12 months. Differences in the absolute values of Kansas City Cardiomyopathy Questionnaire quality of life (KCCQ-QoL) scores during the follow-up were also evaluated. In this study, 75 patients (50.3%) received vericiguat plus GDMT treatment, while 74 patients (49.7%) received GDMT treatment alone. The average age of enrolled patients was 65 years, with approximately 17.4% being female. 33.6% were classified as NYHA class III heart failure, and the average LVEF was 38.11%. Over the 12-month follow-up, the composite endpoint event occurred in 5 (6.67%) of 75 patients in the vericiguat group and 13 (17.57%) of 74 patients in the GDMT group (hazard ratio [HR] 0.31 [95% confidence interval (CI) 0.10–0.96]; P = 0.041). By the end of the follow-up, LVEF improved significantly more with vericiguat (least squares mean [LSM] difference 3.31% [95%CI 0.58%-6.04%]; P = 0.018). From the first month, the vericiguat group demonstrated greater reductions in NT-proBNP (P = 0.004) and improvements in KCCQ-QoL (P = 0.042) than the GDMT group, which were maintained through follow-up. Adverse events were mild with vericiguat, similar to the GDMT group. In the first prospective cohort study focusing on patients with ACS and HFrEF, vericiguat plus GDMT treatment for 12 months reduced the risk of CVD and HHF, while improving cardiac function and quality of life. ClinicalTrials.gov (NCT06321094). Registered on 06 March 2024, prior to the enrollment of the first participant. https://clinicaltrials.gov/search?cond=NCT06321094.