Efficacy of Vericiguat in Acute Heart Failure: A Target Trial Emulation Study

Background In recent trials, vericiguat reduced adverse cardiovascular outcomes in stable or recently worsening chronic heart failure (HF), although data concerning vericiguat use in the population with acute HF remain limited. Methods This target trial emulation study included 205 patients with acute HF with left ventricular ejection fraction ≤45%. Vericiguat was initiated at discharge in 103 patients. Stabilized inverse probability of treatment weighting was used to adjust for baseline differences. The primary outcomes were 180‐day HF rehospitalization and worsening HF events. Secondary end points included New York Heart Association class improvement, cardiac remodeling measured by echocardiography, and safety events. Results After stabilized inverse probability of treatment weighting adjustment, vericiguat significantly reduced 180‐day HF rehospitalization (16.3% versus 34.2%; hazard ratio [HR], 0.43 [95% CI, 0.23–0.80], P =0.01) and worsening HF events were numerically lower in the vericiguat group (21.2% versus 31.1%; HR, 0.64 [95% CI, 0.36–1.15], P =0.13). However, patients treated with vericiguat showed more significant improvement in New York Heart Association class (odds ratio [OR], 0.70 [95% CI, 0.50–0.96], P =0.03), though there was no significant improvement in left ventricular ejection fraction or left ventricular dimensions. The incidence of adverse events such as hypotension, hyperkalemia, and worsening renal function were comparable between the 2 groups. The beneficial effect of vericiguat was consistent across all prespecified subgroups, regardless of chronic HF history or concomitant of quadruple guideline‐directed medical therapy use. Conclusions In patients with acute HF, initiating vericiguat at discharge was observed to be associated with fewer HF rehospitalization events and improvements in New York Heart Association functional class over 180 days. These results suggest that vericiguat may have potential as a treatment option during the vulnerable postacute phase. Registration URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT05799638.