Safety and tolerability of a 5 mg starting dose of vericiguat among patients with heart failure: The VELOCITY study

AimsIn clinical practice, simplifying the number of medication titration steps while maintaining safety may improve the likelihood of patients with heart failure (HF) achieving target doses of guideline‐directed medical therapy (GDMT). The VELOCITY study examined whether removing the 2.5 mg initiation step for vericiguat, and instead initiating therapy at 5 mg daily, would be safe and well‐tolerated.Methods and resultsVELOCITY was a prospective, 2‐week, single‐arm, open‐label phase 2b study that enrolled patients with chronic HF with ejection fraction <45%, with or without a recent (≤6 or >6 months) worsening HF (WHF) event. Patients with systolic blood pressure <100 mmHg, recent symptomatic hypotension, and recent change in background GDMT or diuretic dosing were excluded. Participants were initiated on vericiguat 5 mg daily and followed for the primary endpoint, defined as completion of 2‐week period with maximum 1‐day interruption and without moderate to severe symptomatic hypotension between Visit 1 (Day 1) and Visit 2 (Day 14). Among 106 study patients (mean age 67 years, 28% female), 50% had recent WHF. Background GDMT included 54% prescribed angiotensin receptor–neprilysin inhibitors and 81% prescribed sodium–glucose cotransporter 2 inhibitors. The primary tolerability endpoint was met in 93.4% of patients, including 90.6% of patients in the WHF group and 96.2% of patients in the non‐WHF group. Tolerability of initiating vericiguat 5 mg was generally consistent across the pre‐specified sensitivity and secondary endpoints. When comparing patients initiating vericiguat 2.5 mg daily in VICTORIA with those starting vericiguat 5 mg daily in VELOCITY, the proportion meeting the VELOCITY primary tolerability endpoint was 97.2% in VICTORIA versus 93.4% in VELOCITY.ConclusionsIn the prospective VELOCITY study of patients with chronic HF with ejection fraction <45% who were well‐treated with background GDMT, >9 of 10 patients safely tolerated initiation of vericiguat at the 5 mg/day dose. Findings were generally consistent regardless of recent history of WHF. In the context of safety and tolerability data from prior vericiguat studies, VELOCITY supports a potential update in clinical guidance to include a 5 mg starting dose of vericiguat among patients without recent hypotension.Clinical Trials Registration: ClinicalTrials.gov NCT06195930.