Safety and tolerability of rapid vericiguat initiation and titration alongside GDMT optimization in HFrEF: a prospective cohort study

Heart failure with reduced ejection fraction (HFrEF) remains challenging to manage, particularly in Asian populations. Although vericiguat may complement guideline-directed medical therapy (GDMT), the safety and tolerability of rapid initiation and titration in Chinese patients with HFrEF require further evaluation. This single-center, prospective, single-arm, self-controlled cohort study included 140 patients who received at least 1 dose of vericiguat 5 mg and constituted the treated population; 133 had evaluable 14-day titration and short-term safety data. Patients were monitored for dose-titration success, blood pressure, renal function, electrolytes, hepatic function, hemoglobin, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) over 14 days. Echocardiography was performed at 12 and 20 weeks. The mean age was 61.5 ± 14.2 years, and baseline left ventricular ejection fraction (LVEF) was 32.87 ± 8.51%. On a treated-population basis, 131 of 140 patients (93.6%) achieved the target vericiguat dose of 10 mg by day 14; among patients with evaluable titration data, 131 of 133 (98.5%) achieved target-dose uptitration. Median NT-proBNP decreased by 44.0% from baseline to day 14 ( p < 0.001), without clinically notable blood pressure changes on the day after vericiguat initiation. At 20 weeks, LVEF increased by 8.26% ( p < 0.001), accompanied by reductions in left ventricular diastolic diameter and left atrial diameter. No significant renal, hepatic, or electrolyte safety signals were observed. Rapid initiation of vericiguat 5 mg alongside GDMT optimization showed acceptable short-term safety and tolerability in Chinese patients with HFrEF. These findings support further randomized controlled trials to clarify the independent contribution of vericiguat to cardiac remodeling.