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Efficacy of Vericiguat by Background Guideline-Directed Medical Therapy in the VICTOR Trial

Justin A. Ezekowitz, J. Butler, Derek Cyr, K. Anstrom, Irina Barash, Marc P. Bonaca, S. Corda, Carolyn S. P. Lam et al.

European Journal of Heart Failure, 2026

6,105 participants

Abstract

BACKGROUND AND AIMS

It is uncertain whether the effect of vericiguat varies across levels of background guideline-directed medical therapy (GDMT) in heart failure with reduced ejection fraction (HFrEF).

METHODS

We conducted an exploratory analysis of VICTOR, which enrolled 6105 ambulatory patients with HFrEF without recent worsening. GDMT exposure was classified as basic adherence (on vs. off), indication-corrected adherence (accounting for eligibility and contraindications), and dose-corrected adherence (≥50% target dose). A GDMT intensity score was computed from class-specific dose levels. The primary endpoint was the composite of cardiovascular death or first HF hospitalization. Stratified Cox proportional hazards regression models estimated adjusted hazard ratios for vericiguat versus placebo within GDMT strata, with treatment-by-GDMT interaction test.

RESULTS

Baseline contemporary GDMT use was high (any ARNI/ACE/ARB 93.9%, ARNI 56%, SGLT2i 59%, MRA 78%, beta-blocker 94%). Basic adherence: adjusted HRs for the primary endpoint were similar whether or not patients were on ACEi/ARB, ARNI, any RAS inhibitor, beta-blocker, or SGLT2i. Dose-corrected adherence: adjusted HRs favored vericiguat in ARNI target-dose users (0.73; 0.57-0.93) and in any RAS target-dose users (0.77; 0.64-0.93), with lower risk on vericiguat in patients not meeting MRA target dose (0.67; 0.48-0.95); interaction P-values were nominally significant. The GDMT intensity score showed no significant…

How strong is the evidence?

Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 6,105 participants or records.

How the five levels of evidence work. The level is assigned automatically from the abstract and can be wrong, so check the paper.

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