Vericiguat in heart failure patients: analyzing safety, tolerability, and quality of life via meta-analysis of randomized controlled trials

Abstract Background Heart failure (HF) poses a significant burden on global healthcare systems, necessitating effective therapeutic interventions. Vericiguat, a novel agent targeting soluble guanylate cyclase, has emerged as a potential treatment for HF. Purpose To understand its impact on patient outcomes, including safety, tolerability, and quality of life (QoL). Methods A comprehensive meta-analysis was conducted, encompassing four randomized controlled trials (RCTs) identified through Cochrane CENTRAL, Ovid Medline R, Pubmed, and Web of Science databases up to December 1, 2023. The primary efficacy outcome, Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score (OSS), and the primary safety outcome, drug-related serious adverse events (AEs), were analyzed. Pooled mean differences (MD) and risk ratios (RR) were calculated using inverse variance common-effect model. Results The meta-analysis encompassed 5947 patients across the four RCTs. Our findings indicated that vericiguat did not demonstrate a significant beneficial effect on KCCQ-OSS (MD -0.13, 95% CI -1.32 to 1.05), suggesting no substantial impact on overall QoL, despite a statistically significant improvement in the KCCQ-Physical Limitation Score (PLS) (MD 3.74, 95% CI 0.24 to 7.24) compared to placebo. Notably, vericiguat exhibited a favorable safety and tolerability profile, with comparable risk for AEs leading to death (RR 1.32, 95%CI, 0.58 to 3.03), withdrawal due to AEs (RR 1.08, 95% CI 0.88 to 1.32) or serious AEs (RR 1,18, 95%CI, 0,50; 2,80), renal and urinary disorders (RR 0.99, 95% CI 0.88 to 1.11), symptomatic hypotension (RR 1.17, 95% CI 0.98 to 1.40), and acute kidney injury (RR 1.04, 95% CI 0.83 to 1.31) compared to placebo. Conclusion Vericiguat demonstrates promising safety and tolerability profiles in patients with HF. While our analysis reveals significant improvement in KCCQ-PLS, indicating enhanced physical limitation scores, the lack of statistically significant impact on overall QoL raises questions about its comprehensive efficacy. These findings underscore the need for further research to elucidate the holistic impact of vericiguat on patient-reported outcomes in heart failure management.Forest plot of quality of life outcomesForest plot of safety outcomes