Key result
Vericiguat increases symptomatic hypotension risk ~24% vs placebo but remains well-tolerated in HFrEF.
Why the study?
The efficacy and safety of vericiguat in patients with chronic HFrEF on contemporary therapies without recent worsening were investigated, with uncertainty about susceptibility to symptomatic hypotension in some subgroups.
Does vericiguat increase symptomatic hypotension or alter efficacy in vulnerable subgroups of patients with chronic HFrEF compared to placebo?
RCT
Does vericiguat increase symptomatic hypotension or alter efficacy in vulnerable subgroups of patients with chronic HFrEF compared to placebo?
Vericiguat is well-tolerated in a broad HFrEF population on contemporary therapy, with only a slight decrease in SBP and a modest increase in symptomatic hypotension that does not compromise its consistent efficacy.
Modest hypotension increase with vericiguat does not limit use in HFrEF; confirms tolerability on contemporary therapy without compromising efficacy.
AIMS: The efficacy and safety of vericiguat in patients with chronic heart failure with reduced ejection fraction (HFrEF) on contemporary heart failure (HF) therapies and without recent worsening was investigated in the VICTOR trial, yet some subgroups may be more susceptible to symptomatic hypotension. METHODS AND RESULTS: Among VICTOR trial participants that received at least one dose of study drug or placebo, we describe the systolic blood pressure (SBP) trajectories over time (mean change from baseline), symptomatic hypotension events and efficacy of vericiguat in potentially vulnerable patient subgroups: lower baseline blood pressure (SBP ≤110 mmHg), older patients (>75 years) and those taking angiotensin receptor-neprilysin inhibitors (ARNI) or sodium-glucose co-transporter 2 inhibitors (SGLT2i) at baseline. The efficacy outcomes of cardiovascular death and HF hospitalization and cardiovascular death alone across baseline SBP were examined using Cox proportional hazards models. Overall SBP trajectories showed a small initial decline from baseline in vericiguat-treated patients compared with placebo (placebo-corrected differences of -1.17 [-1.84, -0.50], p = 0.0007) that was relatively stable throughout follow-up. This trajectory was similar in those >75 years (vs. younger) as well as those receiving ARNI or SGLT2i (as compared with those not receiving these) or those with SBP ≤110 mmHg at baseline (compared with >110 mmHg). Symptomatic hypotension occurred in 11.3% of vericiguat-treated patients compared with 9.2% of placebo-treated patients with an adjusted hazard ratio of 1.24 (95% confidence interval 1.06-1.46), which was similar across age, SBP, SGLT2i and ARNI groups (all interaction p >0.05). The treatment effect of vericiguat compared with placebo on the efficacy outcomes was similar across the spectrum of baseline SBP (both interaction p >0.15). CONCLUSIONS: Vericiguat showed a slight adjusted decrease in SBP and resulted in more symptomatic hypotension compared with placebo but was overall well-tolerated in a broad population with HFrEF on contemporary therapy even among those predisposed to hypotension. Treatment effects on efficacy outcomes were consistent regardless of baseline SBP.
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Mentz et al. (2025) conducted an RCT in Chronic heart failure with reduced ejection fraction (HFrEF). Vericiguat vs. Placebo was evaluated on Symptomatic hypotension (HR 1.24, 95% CI 1.06-1.46). Vericiguat resulted in more symptomatic hypotension compared with placebo (11.3% vs 9.2%; HR 1.24, 95% CI 1.06-1.46) but was overall well-tolerated in patients with HFrEF on contemporary therapy.
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