Vericiguat Treatment Benefit in Heart Failure Independent of Patient Sex and Age

Women at least 75 years of age with heart failure (HF) have a nominally better prognosis than men despite receiving less intense background therapy. The benefit that all patients with HF received from treatment with vericiguat was independent of sex and age. These are among the post hoc analysis findings published in JACC: Heart Failure.

The analysis aimed to characterize the associations of sex and age with background standard HF therapies (guideline-directed medical therapy and HF devices), clinical features, outcomes, and response to treatment with vericiguat among participants in the VICTORIA trial (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction [HFrEF]).

VICTORIA (ClinicalTrials.gov Identifier: NCT02861534) was an international, multicenter, placebo-controlled trial exploring the efficacy and safety of vericiguat in symptomatic chronic HF with ejection fractions (EFs) less than 45% and worsening HF events within 6 months. Patients (N=5050) were randomly assigned 1:1 to start 2.5 mg vericiguat or matching placebo, then up-titrated to 5 mg then to 10 mg once daily. Composite of time to first HF hospitalization or cardiovascular death was the primary endpoint.

In the post hoc analysis, study authors compared clinical characteristics across sex (24% women) and age groups (younger than 65 [n=1873], 65 to younger than 75 [n=1609], 75 and older [n=1568] years of age). The proportion of women in age groups increased from 20% to 24% to 28%, respectively. Compared with men, women in each group had shorter intervals from HF diagnosis to randomization, higher EFs, and lower burden of coronary artery disease, hyperlipidemia, and atrial fibrillation, but similar N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels.

Study authors found that overall, when compared with younger patients, individuals 75 years of age had worse kidney function, higher NT-proBNP levels, and more class III and class IV symptoms, but had the lowest use of triple therapy (guideline-directed medical therapy). Older patients were less likely to achieve target doses of triple therapy, but by age, there were no sex differences in triple therapy.

Study authors noted men at least 75 years of age were more than twice as likely to receive defibrillators and 65% more likely than women to undergo cardiac resynchronization. Women compared with men across all age groups had nominally lower primary composite outcomes.

There were no between-sex differences in any age group in vericiguat dosing, and age did not modify the beneficial effect on the primary outcome (continuous age, P_interaction =0.169; categorical age, P_interaction =0.189), nor did sex (P_{3-way interaction} =0.847).

Current post hoc analysis limitations include the post hoc design and selection bias.

“Although elderly women received less intense background HF therapy than men, their prognosis was nominally better,” study authors concluded, adding, “The benefit of vericiguat was independent of age and sex.”

Disclosure: This research was supported by Merck Sharp and Dohme Corp and Bayer AG. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.