Treatment with vericiguat was not found to improve physical limitation in patients with heart failure with preserved ejection fraction (HFpEF) and recent decompensation, according to a study published in the Journal of the American Medical Association.
Patients with vs without HFpEF are at higher risk for hospitalization, mortality and reduced quality of life as a result of functional limitations. Investigators sought to evaluate the safety and efficacy of vericiguat, an oral soluble guanylate cyclase stimulator, on the physical limitation score (PLS; scale, 0-100) of the Kansas City Cardiomyopathy Questionnaire (KCCQ).
In this international multicenter phase 2b randomized, double-blind, placebo-controlled trial (VITALITY-HFpEF; ClinicalTrials.gov Identifier: NCT03547583), 789 participants (mean age, 72.7±9.4 years; 100% >45 years; 48.8% women) were enrolled between June 2018 and March 2019. Of these participants, 761 (96.5%) completed the study. All participants had a history of chronic HFpEF (ie, left ventricular [LV] EF ≥45%) with class II (59%) or III (41%) New York Heart Association symptoms and elevated natriuretic peptide concentrations. In addition, all patients had experienced decompensation (ie, hospitalization for HF or HF requiring intravenous diuretic therapy without a need for hospitalization) within 6 months of enrollment.
Participants were randomly assigned 1:1:1 to receive orally: 15 mg vericiguat (n=264), 10 mg vericiguat (n=263), or placebo (n=262) once daily. Vericiguat was uptitrated from a starting dose of 2.5 mg per day, and placebo was sham titrated. The study’s primary endpoint was the change from baseline in the PLS at 24 weeks. The secondary endpoint was the change in 6-minute walking distance (6MWD) over the same period.
At baseline, the cohort’s median N-terminal pro-brain natriuretic peptide level was 1403 pg/mL, and the mean LV EF was 56%.
The mean baseline KCCQ PLS were the following: 15 mg vericiguat, 60.0; 10 mg vericiguat, 57.3; and placebo, 59.0. At 24 weeks, these scores were 68.3, 69.0 and 67.1, respectively (least-squares mean changes: 5.5, 6.4 and 6.9, respectively). The least-squares mean score differences were: for the 15 mg vericiguat vs placebo group: -1.5 (95% CI, -5.5 to 2.5; P = .47), and for the 10 mg vericiguat vs placebo group: -0.5 (95% CI, -4.6 to 3.5; P = .80) after multivariable adjustment.
Mean distances in the 6MWD at baseline were: 295.0 m in the 15 mg vericiguat group, 292.1 m in the 10 mg vericiguat group, and 295.8 m in the placebo group. After 24 weeks of treatment, the respective 6MWD distances for these groups were: 311.8 m, 318.3 m and 311.4 m (least-squares mean changes: 5.0 m, 8.7 m and 10.5 m, respectively). The least-squares mean score differences were: for 15 mg vericiguat vs placebo, -5.5 m (95% CI, -19.7 m to 8.8 m; P = .45); and for 10 mg vericiguat vs placebo, -1.8 m (95% CI, -16.2 m to 12.6 m; P = .81).
In terms of safety, symptomatic hypotension occurred in 6.4%, 4.2% and 3.4% of the 15 mg vericiguat, 10 mg vericiguat, and placebo groups, respectively, and syncope occurred in 1.5%, 0.8% and 0.4%, respectively. Total adverse event rates were 65.2%, 62.2% and 65.6% in these 3 treatment groups, respectively.
Study limitations include possible HFpEF misdiagnoses, small adverse event numbers that did not allow to determine the optimal method for handling missing data.
“It appears that the natural history of KCCQ improvement following recent HFpEF hospitalization remains poorly understood and warrants future study,” noted the authors.
Funding and Conflicts of Interest Disclosures:
Funding for this research was provided by Bayer and Merck Sharp & Dohme Corp, a subsidiary of Merck & Co Inc.
Please see original article for conflict of interest declarations.
Armstrong PW, Lam CSP, Anstrom KJ, et al. Effect of vericiguat vs placebo on quality of life in patients with heart failure and preserved ejection fraction. JAMA. 2020;324(15):1512-1521. doi:10.1001/jama.2020.15922