Starting vericiguat at 5 mg, instead of 2.5 mg, is safe in HF with reduced EF
ESC Heart Failure 2025 – In the single-arm VELOCITY study among patients with chronic HF and LVEF <45%, a vericiguat starting dose of 5 mg daily was safely tolerated by >90% of the participants, regardless of recent worsening HF.
This summary is based on the presentation of Stephen Greene, MD (Durham, NC, USA) at the ESC Heart Failure Congress 2025 - Safety and tolerability of a 5 mg starting dose of vericiguat among patients with heart failure: the VELOCITY study.
Introduction and methods
In routine clinical practice, most patients with HFrEF do not achieve target doses of GDMTs, and dose increases over time are only seen in a few patients. Clinical inertia is thought to be one of the main barriers to target dosing.
Vericiguat, a soluble guanylate cyclase stimulator, is approved for the treatment of worsening HF (WHF) in patients with LVEF <45%. The current label recommends a starting dose of 2.5 mg daily, uptitrating to 5 mg at approximately 2 weeks, and a target dose of 10 mg at 4 weeks. The VELOCITY study examined whether omitting the 2.5-mg dosing step and instead initiating vericiguat treatment at 5 mg daily is safe and well tolerated by HF patients with LVEF <45%. The VELOCITY study was a multinational, prospective, single-arm, open-label, phase 2b study in which 106 patients with chronic HF, LVEF <45%, systolic blood pressure ≥100 mHg, and no symptomatic hypotension 4 weeks prior to screening started treatment with vericiguat 5 mg daily for 2 weeks. Of them, 53 (50%) had a recent (≤6 months) WHF event. Background GDMT prescriptions included ARNIs (54% of the patients), SGLT2 inhibitors (81%), and MRAs (82%).
The primary endpoint was tolerability of the 5-mg starting dose of vericiguat, defined as completion of the 2-week period with interruption lasting ≤1 day and with no moderate-to-severe symptomatic hypotension. Secondary endpoints were completion of the 2-week period with no adverse events related to the use of the study drug and completion of the 2-week period with either continuous intake of vericiguat or resumption after temporary interruption.
To add further context, patients with chronic HF, LVEF <45%, and recent WHF who were initiated on vericiguat 2.5 mg daily in the VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction) trial (n=2519) were analyzed for the VELOCITY primary endpoint.
Main results
- Overall, 99 patients (93.4%) met the primary tolerability endpoint, including 48 of the 53 patients with a recent WHF event (90.6%) and 51 in the group with no such event (96.2%).
- By comparison, 97.2% of the patients in the VICTORIA trial who were initiated on vericiguat 2.5 mg met the 2-week primary tolerability endpoint, including 97.2% of those with recent WHF.
- Regarding the secondary endpoints, 96 patients (90.6%) in the VELOCITY study completed the 2-week period with no adverse events related to vericiguat and 102 (96.2%) completed this period with no interruption of vericiguat treatment or with only temporary interruption.
- Treatment-emergent adverse events were reported in 14 VELOCITY study patients (13.2%), almost all of which were mild or moderate in severity. Four patients (3.8%) experienced a treatment-emergent adverse event leading to discontinuation of the study drug (2 due to symptomatic hypotension). There were no deaths.
- In the VELOCITY study, the mean change in systolic blood pressure from baseline to 2 weeks was −3.2 mmHg, which was identical to the reduction seen in the VICTORIA trial (difference with placebo: –1.1 mmHg).
Conclusion
In the open-label single-arm VELOCITY study among patients with chronic HF and LVEF <45% who were well-treated with background GDMT, initiation of treatment with vericiguat 5 mg daily was safe and well tolerated by >90% of the participants, regardless of recent WHF. According to Dr. Greene, “if we can safely start study therapy closer to target and then have a one-step titration pathway, this will perhaps help us better combat clinical inertia and get more patients to the 10-mg target dose.”
- Our reporting is based on the information provided at the ESC Heart Failure Congress 2025 -