Randomized Controlled Trials of Zhigancao Decoction Combined With Metoprolol in the Treatment of Arrhythmia: A Systematic Review and Meta-Analysis

Objective: Cardiac arrhythmia remains a major public health problem worldwide. Combinations of traditional medicine (TM) and conventional medicine (CM) have been used for arrhythmia treatment, yet the effectiveness and safety of many TM preparations can be controversial. We analyzed the safety and effectiveness of Zhigancao decoction (ZGCD) combined with metoprolol for arrhythmia treatment.Methods: Systematic searches for randomized clinical trials (RCTs) were conducted in eight databases (January 2010-September 2020) without language restrictions. According to the Cochrane system evaluation method, the overall effectiveness and safety were evaluated by meta-analysis using Review Manager software (version 5.3), and publication bias was qualitatively analyzed using STATA 12.0.Results: A total of 39 RCTs were incorporated, including 4,260 patients with arrhythmia, with 2,133 patients in the experimental group (ZGCD + metoprolol, ZGCD + BB) and 2,127 patients in the control group (metoprolol only, BB). Meta-analysis revealed that compared with BB, ZGCD + BB could significantly increase the total efficacy (OR = 4.74, 95% CI: 3.78-5.94, P < 0.01) and lower the incidences of arrhythmia (MD = -3.39, 95% CI: -4.09 to -2.68, P < 0.01). Moreover, mean HR reductions were reported in patients receiving ZGCD + BB the ZGCD + BB group (MD = -8.48, 95% CI: -10.98 to -5.97, P < 0.01) and a decrease in TCM symptoms were reported also (MD = -2.92, 95% CI: -3.08 to -2.76, P < 0.01). The incidence of adverse events was lower in patients treated with ZGCD + BB (RR = 0.36, 95% CI: 0.26-0.51, P < 0.01). These results appeared consistent across common arrhythmias. Nevertheless, the majority of included studies were unable to be formally assessed for bias, and funnel-plot analysis implied a moderate risk of publication bias.Conclusion: ZGCD + BB appeared to demonstrate good efficacy and fewer adverse reactions compared to BB in the treatment of arrhythmia, and this may represent a useful complementary therapy. However, our findings must be cautiously evaluated because of the small sample size and low quality of the clinic trials cited in the review. Rigorous and large-scale RCTs are warranted in the future to confirm these results.