Soluble guanylate cyclase stimulators for heart failure: a network meta-analysis and subgroup analyses of reduced and preserved ejection fraction

Abstract

Background Soluble guanylate cyclase (sGC) stimulators have been investigated for heart failure (HF) in several randomized controlled trials (RCTs). However, its place in the management guidelines of either HFrEF or HfpEF is still inconclusive. Methods We conducted a network meta-analysis synthesizing RCTs investigating sGC for HF management, which were retrieved by systematically searching five databases until January 24th, 2023. Dichotomous outcomes were pooled using risk ratio (RR) along with confidence interval (CI). Results Eight RCTs with a total of 7307 patients were included. Vericiguat 10 mg significantly reduced the composite cardiovascular (CVS) mortality and HF hospitalization in HF (RR: 0.88, 95% CI [0.79; 0.98]) and in HFrEF (RR: 0.87, 95% CI [0.78; 0.97]); however, it was not effective in HFpEF (RR: 0.69, 95% CI [0.15; 3.05]). Also, vericiguat 10 mg showed no difference compared to placebo regarding the incidence of all-cause mortality (RR: 0.96, 95% CI [0.84; 1.10]), any adverse events (AEs) (RR: 0.94, 95% CI [0.83; 1.07]), any serious AEs (RR: 0.91, 95% CI [0.81; 1.01]), and any AEs leading to drug discontinuation (RR: 1.14, 95% CI [0.92; 1.40]). Conclusion Vericiguat 10 mg was effective in reducing the composite CVS mortality and HF hospitalization, with an acceptable safety profile. This was only observed in HFrEF patients, but not in HFpEF patients. However, our data regarding other agents (riociguat and praliciguat) and HFpEF can be underpowered, warranting further RCTs to clarify vericiguat 10 mg place in HFrEF management guidelines and to investigate sGC stimulators for HFpEF in large-scale trials.

Drug Therapy for Acute and Chronic Heart Failure with Preserved Ejection Fraction with Hypertension: A State-of-the-Art Review

“…The largest difference in DBP at 12 weeks was between the placebo and 2.5 mg vericiguat groups (−4.1 mmHg; 95% CI −7.6 to −0.6 mmHg) VITALITY-HFpEF trial [ 125 ]: Among the patients with HFpEF and recent decompensation, 24-week treatment with vericiguat at either 15-mg/day or 10-mg/day dosages compared with placebo did not improve the physical limitation score of the Kansas City Cardiomyopathy Questionnaire LVEF ≥ 45% 92% For all study participants ( N = 789): SBP 129 mmHg, with > 70% above 120 mmHg DBP 73 mmHg Mean changes in SBP at 24 weeks were −3.1 (SD, 14.94) mmHg in the 15-mg/day vericiguat group, −3.8 (SD 4.01) mmHg in the 10-mg/day vericiguat group, and −1.2 (SD 15.42) mmHg in the placebo group. There were no significant changes between the groups in DBP Abuelazm et al 2024 [ 128 ]: Vericiguat 10 mg was effective in reducing the composite CVS mortality and HF hospitalization, with an acceptable safety profile. This was only observed in HFrEF patients, but not in HFpEF patients.…”

“…Conversely, the VITALITY-HFpEF trial, which investigated the effects of vericiguat treatment over 24 weeks in patients with HFpEF following recent decompensation, did not demonstrate improvement in the KCCQ physical limitation score [ 125 – 127 ]. A recent network meta-analysis of eight randomized controlled trials with a total of 7307 patients showed that vericiguat did not reduce the composite of cardiovascular mortality and HF hospitalization in patients with HFpEF [ 128 ]. These conflicting findings highlight the need for further research to better understand the role of sGC stimulators in the management of HFpEF and their potential implications for improving patient outcomes.…”