Xinkeshu for coronary heart disease complicated with anxiety or depression: A meta-analysis of randomized controlled trials

Ethnopharmacological relevance: The incidence of coronary heart disease (CHD) complicated with anxiety or depression is increasing year by year. However, many anti-anxiety drugs or antidepressants have a certain degree of adverse reactions and are not easily accepted by patients. Xinkeshu (XKS), as a proprietary Chinese patent medicine with "psycho-cardiology" effect, is one of the commonly used drugs in the treatment of CHD complicated with anxiety or depression in China.Aim of the study: To systematically evaluate the efficacy and safety of XKS for CHD complicated with anxiety or depression.Methods: Nine different electronic databases were independently searched to include randomized controlled trials (RCTs) of XKS for CHD complicated with anxiety or depression published from inception to February 2022, and the methodological quality was evaluated using the bias risk assessment tool from Cochrane Handbook 5.0 and the modified Jadad scale. Meta-analysis was performed using RevMan 5.3 and Stata 16.0 software. The GRADE Profiler 3.6.1 and TSA 0.9.5.10 beta were adopted to evaluate the certainty and conclusiveness of the evidence.Results: A total of 18 RCTs involving 1907 subjects were included. There were 956 subjects in the XKS group and 951 subjects in the control group. Baseline conditions were consistent and comparable between the groups. Compared with single-use western medicine (WM), XKS combined with WM significantly reduced scores of Hamilton Anxiety Scale (HAMA) [Mean difference (MD) =-7.60, 95% confidence interval (95% CI) (-10.37,-4.83), P < 0.000 01], Zung Self-rating Anxiety Scale (SAS) [MD =-10.05, 95% CI (-12.70,-7.41), P < 0.000 01], Hamilton Depression Scale (HAMD) [MD =-6.74, 95% CI (-11.58,-1.90), P = 0.006], and Zung Self -rating Depression Scale (SDS) [MD =-10.75, 95% CI (-17.05,-4.45), P = 0.000 8], as well as improved clin-ical effective rate [odds ratio (OR) = 4.24, 95% CI (2.47, 7.27), P < 0.000 01]. In terms of safety, 4 studies reported the adverse reactions in detail. The severity was mild and symptoms disappeared after treatment.Conclusion: Current evidence indicates that XKS may be effective and safe in the treatment of patients with CHD complicated with anxiety or depression. Since the quality of the literature included in this study was generally low, there is an urgent need for more RCTs with high quality, low bias risk and sufficient sample size to validate our conclusions.