Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 May 19.
doi: 10.1002/ejhf.3699. Online ahead of print.

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

Stephen J Greene  1   2 , Stefano Corda  3 , Ciaran J McMullan  4 , Giovanni Palombo  3 , Christina Schooss  5 , Vanja Vlajnic  6 , Katrin Walkamp  7 , Michele Senni  8 ; on behalf of the VELOCITY investigators
Affiliations

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

Stephen J Greene et al. Eur J Heart Fail. .

Abstract

Aims: In 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 results: VELOCITY 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.

Conclusions: In 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.

Keywords: Heart failure; Medication; Titration; Vericiguat.

PubMed Disclaimer

References

    1. McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al.; ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC).With the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 2022;24:4–131. https://doi.org/10.1002/ejhf.2333
    1. Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol 2022;79:e263–e421. https://doi.org/10.1016/j.jacc.2021.12.012
    1. Greene SJ, Fonarow GC, DeVore AD, Sharma PP, Vaduganathan M, Albert NM, et al. Titration of medical therapy for heart failure with reduced ejection fraction. J Am Coll Cardiol 2019;73:2365–2383. https://doi.org/10.1016/j.jacc.2019.02.015
    1. Greene SJ, Ezekowitz JA, Anstrom KJ, Demyanenko V, Givertz MM, Pina IL, et al. Medical therapy during hospitalization for heart failure with reduced ejection fraction: The VICTORIA registry. J Card Fail 2022;28:1063–1077. https://doi.org/10.1016/j.cardfail.2022.02.011
    1. Greene SJ, Bash LD, Tebbs KW, Hancock LN, Barlow SG, Coyle CR. Physician‐reported reasons for not initiating guideline‐directed medical therapy for heart failure. JACC Heart Fail 2024;12:2120–2122. https://doi.org/10.1016/j.jchf.2024.08.002

Associated data

LinkOut - more resources