Initiation, titration, and safety of vericiguat for treatment of heart failure in United States clinical practice

Study objective To evaluate the following among new users of vericiguat: up-titration patterns, factors associated with up-titration, occurrence of hypotension/syncope, predictors of hypotension/syncope. Design Retrospective cohort study (linked claims and electronic health record data). Setting US clinical practice. Participants 1361 new users of vericiguat. Interventions N/A. Main outcome measures Vericiguat starting dose, up-titration patterns and predictors, occurrence and predictors of hypotension/syncope, over a 3-month follow-up period. Results Among 1361 new users of vericiguat, 770 (57%) initiated a starting dose of 2.5 mg/day, 330 (24%) initiated a dose of 5 mg/day, and 261 (19%) initiated a dose of 10 mg/day. Over 3-month follow-up, the 10 mg target dose was reached by 349 (26%) patients. Among these patients, the median time to reach the 10 mg dose was 60 days among 2.5 mg/day starters, and 41 days among 5 mg/day starters. Among the 2.5 mg starters, 68% had no up-titration. Among patients initiating either the 2.5 mg/day or 5 mg/day dose, a starting dose of 5 mg (vs. 2.5 mg) was the only significant predictor for reaching the 10 mg dose; adjusted hazard ratio 2.89 (95% CI: 1.86, 4.49, p < 0.0001). Overall, 130 patients (9.6%) had a hypotension event and 67 patients (4.9%) had a syncope event. History of hypotension was the strongest independent predictor of hypotension/syncope events (adj. HR 2.85, 95% CI: 1.96, 4.13, p < 0.0001). A > 2.5 mg/day vericiguat starting dose was not associated with the occurrence of hypotension/syncope (vs. 2.5 mg/day); adj. HR 0.82, 95% C.I. (0.58, 1.16). Conclusion Vericiguat users initiated on the 5 mg/day dose were considerably more likely to reach the target dose of 10 mg/day vs. those started on the recommended 2.5 mg/day dose, without excess risk of hypotension or syncope.