Efficacy and Safety of Xinmailong Injection for Chronic Heart Failure: A Systematic Review and Meta-Analysis for Randomized Clinical Trials.

Abstract

Introduction: Xinmailong injection (XMLI) is a common Traditional Chinese Medicine for treating chronic heart failure (CHF) in China. However, strong evidence-based medical evidence for XMLI is lacking. Purpose: To evaluate the efficacy and safety of XMLI in patients with CHF. Methods: PubMed, the Cochrane Library, Web of Science, Embase, China National Knowledge Infrastructure, Wanfang Database, VIP Database for Chinese Technical Periodicals, and Chinese Biomedical Literature Database were searched to identify randomized controlled trials (RCTs) of XMLI for CHF from the inception of the databases to November 2, 2024. The Cochrane risk of bias tool for randomized trials (RoB 2) was used to evaluate the quality of studies, and STATA 17.0 software was used to perform a meta-analysis of left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), brain natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptide (NT-proBNP), 6-min walking distance (6-MWD), and adverse reactions. The quality of evidence was rated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results: Twenty-three RCTs comprising 2643 patients were included. Meta-analysis showed that compared with those under conventional Western drug treatment (CWT), combined XMLI and CWT effectively increased LVEF (mean difference [MD] = 6.66, 95% confidence interval [CI] [5.23, 8.09], Z = 9.12, p < 0.001) and 6-MWD (MD = 44.01, 95% CI [28.63,59.38], Z = 5.61, p < 0.001) and reduced LVEDD (MD = -4.19, 95% CI [-5.55, -2.83], Z = -6.05, p < 0.001), BNP (MD = -178.84, 95% CI [-230.29, -127.40], Z = -6.81, p < 0.001), and NT-proBNP (MD = -490.95, 95% CI [-729.40, -252.50], Z = -4.04, p < 0.001). There were no statistically significant differences between the two adverse reactions (risk ratio [RR] = 1.47, 95% CI [0.73,2.99], Z = 1.08, p = 0.28). The GRADE assessment rated adverse reactions as moderate-quality evidence, while LVEDD, BNP, NT-proBNP, and 6-MWD were classified as low-quality evidence, and LVEF was categorized as very low-quality evidence. Conclusions: This systematic review demonstrates that combining XMLI with CWT is effective and safe for managing CHF and offers an evidence-based adjunctive therapeutic strategy. Further high-quality clinical trials are required to investigate the prognostic implications and long-term outcomes.