Guideline-directed medical therapy and hypotension after initiation of vericiguat: Insights from the VERIFY-HF study

BACKGROUND: Guidelines recommend vericiguat initiation in patients with heart failure (HF) with reduced ejection fraction who have already been prescribed guideline-directed medical therapy (GDMT). However, few studies have examined the safety and tolerability of vericiguat according to baseline GDMT in clinical practice. METHODS: This retrospective observational study used data from a multicenter registry of patients who initiated vericiguat between June 2021 and September 2023. Patients with left ventricular ejection fraction <45% who had at least one GDMT at baseline were divided into two groups according to the number of GDMTs: the quadruple GDMT and non-quadruple GDMT groups. The association between baseline GDMT and hypotension and drug discontinuation within 90 days after vericiguat initiation was analyzed. RESULTS: Among 791 patients included, 398 (50.3%), 220 (27.8%), 127 (16.1%), and 46 (5.8%) patients were prescribed quadruple, triple, double, and single GDMTs, respectively. The median (interquartile range) baseline systolic blood pressure was similar between the non-quadruple GDMT [104 (92-118) mmHg] and the quadruple GDMT [102 (90-115) mmHg] groups (p = 0.11). Patients in the non-quadruple GDMT group were older, had a lower proportion of a history of HF hospitalization, and higher B-type natriuretic peptide levels. Hypotension occurred in 28.2% in the non-quadruple GDMT group and 22.4% in the quadruple GDMT group (p = 0.057), and the adjusted odds ratio for hypotension was not different between groups (odds ratio 1.16, 95% confidence interval 0.80-1.67; p = 0.43). Drug discontinuation occurred more frequently in the non-quadruple GDMT group than in the quadruple GDMT group (16.5% vs 10.3%, p = 0.01), with hypotension accounting for a minority of discontinuations. CONCLUSIONS: Baseline non-quadruple GDMT was not associated with hypotension after vericiguat initiation, suggesting that vericiguat may be safely added even when quadruple GDMT has not been achieved.