Effectiveness and Safety of Eleven Chinese Patent Medicines Combined with Atorvastatin in the Treatment of Hyperlipidemia: A Network Meta-Analysis of Randomized Controlled Trials

Zeyang Shi ¹ Wei Zheng ² Zhijun Bu ¹ Xian Zhou ³ Xuefeng Wang ¹ Yike Song ¹ Jialin Sun ⁴ Jian-Ping Liu ¹ Zhaolan Liu ^1*

• ¹ Centre for Evidence-Based Chinese Medicine, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
• ² Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, Beijing Municipality, China
• ³ NICM Health Research Institute, Western Sydney University, Westmead, New South Wales, Australia
• ⁴ School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China

Background: RCTs suggested that combining Chinese patent medicines with atorvastatin exhibited superior effectiveness in treating hyperlipidemia with reduced adverse reactions. However, the evidence regarding the clinical effectiveness and safety was not assessed to make informed decision in clinical practice. Methods: Eight databases were searched from inception to April 2024. The risk of bias of the included RCTs was assessed using the ROB 2.0 tool recommended by the Cochrane Handbook. The surface under the cumulative ranking curve probability values were used to rank the treatment measures, and the Confidence in Network Meta-Analysis software was used to assess the grading of evidence.Results: A total of 23 RCTs involving 2184 patients with hyperlipidemia were included. Hedan combined with atorvastatin showed the highest clinical effectiveness with an RR of 1.58 (95% CI: [1.14, 2.12]) (SUCRA: 80.36%), the lowest post-treatment low-density lipoprotein cholesterol level with an MD of -8.13(95% CI: [-9.70, -6.57]) (SUCRA: 3.37%), and the lowest post-treatment triglyceride level with an MD of -6.43(95% CI: [-7.71, -5.16]) (SUCRA: 0.33%). Dantian Jiangzhi Granules demonstrated the lowest post-treatment total cholesterol level with an MD of -2.22(95% CI: [-2.60, -1.83]) (SUCRA: 12.6%), while Xuezhikang Capsules displayed the highest post-treatment high-density lipoprotein cholesterol level with an MD of 1.61(95% CI: [0.82, 2.39]) (SUCRA: 79.87%). However, it is important to note that most of the included studies showed "some concerns" regarding the risk of bias based on ROB 2.0. According to CINeMA, most confidence rating results were classified as "low".Conclusion:Compared to atorvastatin alone, the combination of Chinese patent medicines with atorvastatin demonstrated superior effectiveness in treating hyperlipidemia. Among these, Hedan (tablets or capsules) exhibited the greatest overall benefit, significantly reducing TG and LDL-C levels. Dantian Jiangzhi Granules had the most pronounced effect in lowering TC, while Xuezhikang was most effective in reducing HDL-C level. Although Xuezhikang is well-documented as lipid-lowering agent, the findings of this study suggest that hyperlipidemia treatment should be tailored to individual blood lipid profiles. Additionally, for drugs with limited evidence of efficacy and safety, larger randomized controlled trials and further pharmacological studies are necessary to valid these results.