TOPLINE:

Vericiguat demonstrated more favorable effects in reducing the risk for repeat events of heart failure hospitalization (HFH) and death in ambulatory patients with HF with reduced ejection fraction (HFrEF), when mortality events that occurred after HFH were also considered in the analysis. 

METHODOLOGY:

• In the VICTOR trial, vericiguat did not significantly delay HFH or cardiovascular death (CVD), but signs of potential benefits were observed. Analyses based on the time-to-first event may have missed part of the benefit, as early events may not be fully preventable with treatment.
• Researchers conducted a post hoc analysis of the VICTOR trial to evaluate whether composite endpoints that included recurrent events could provide more comprehensive insight into the treatment effect of vericiguat in VICTOR because they would capture mortality events that occurred after early HFH.
• The trial enrolled 6105 ambulatory patients with HFrEF and no recent worsening HF; 3053 were randomly assigned to receive vericiguat (target dose of 10 mg) and 3052 to receive placebo.
• The area under the curve (AUC) method was used to estimate the cumulative burden of total events at 30 months, with treatment effect expressed as the difference in AUC and the AUC ratio between groups.

TAKEAWAY:

• Patients who received vericiguat had fewer events than those who received placebo for both the composite of total HFH and CVD (841 vs 943; rate ratio [RR], 0.88; 95% CI, 0.76-1.01) and the composite of total HFH and all-cause death (926 vs 1037; RR, 0.88; 95% CI, 0.77-1.00).
• At 30 months, the difference in AUC values favored vericiguat over placebo for total HFH (-0.048; 95% CI, -0.089 to -0.006), the composite of CVD and total HFH (-0.091; 95% CI, -0.143 to -0.038), and the composite of all-cause mortality and total HFH (-0.083; 95% CI, -0.139 to -0.028).
• At 30 months, the AUC ratio was 0.85 for total HFH (95% CI, 0.73-0.98), 0.82 for CVD and total HFH (95% CI, 0.73-0.92), and 0.85 for all-cause mortality and total HFH (95% CI, 0.76-0.95).

IN PRACTICE:

“We observe more directionally favorable effects on the reported total HFH and CVD endpoint, which allows incorporation of post HFH events that were censored and ignored in the original time-to-first event composite,” the authors wrote.

SOURCE:

The study was led by Yogesh N.V. Reddy, MBBS, Department of Cardiovascular Medicine, Mayo Clinic in Rochester, Minnesota. It was published online on June 12 in JACC: Heart Failure.

LIMITATIONS:

The authors could not rule out the possibility of a false positive result in the nominally significant AUC findings, particularly considering the large number of events contributing to the observed effect estimates.

DISCLOSURES:

The study received support from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., and Bayer AG. Some authors, including the lead author, reported receiving grants; consulting fees; and payments or honoraria for lectures, presentations and serving on advisory or data safety monitoring boards of various pharmaceutical and medical device companies, including the funding agencies. One of the authors declared being an employee of Merck Sharp & Dohme LLC and possibly owning stock and/or stock options in Merck & Co., Inc. Detailed disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.