Li Wanying, Wang Ding, Lin Caiyue, Cai Tongze, Zhao Mei, Liang Liuguan, Zhao Xingxing, He Xin, Liang Xiaoyue, Zheng Jinghui
Graduate School, Guangxi University of Chinese Medicine, Nanning, Guangxi, China.
Department of Cardiology, The First People's Hospital of Nanning, Nanning, Guangxi, China.
Cardiovasc Ther. 2025 Jun 10;2025:6684099. doi: 10.1155/cdr/6684099. eCollection 2025.
In clinical practice, patients often avoid or cease statin use due to adverse reactions or noncompliance. To elucidate statin adverse reactions, their variability across diseases, and the factors influencing them, we conducted a high-quality clinical trial-based meta-analysis. Clinical randomized controlled trials involving statins and detailed recording of adverse reactions in the following three databases: PubMed, Embase, and Cochrane Library were included. The retrieval was completed by January 31, 2024. All studies will use the ROB2 scale for bias risk assessment. We had included a total of 41 studies, involving a collective sample size of 64,728 individuals. In patients with hyperlipidemia, there was no difference in the overall incidence of total adverse events among four types of statins ( = 0.37). Simvastatin 40 mg had fewer statin-related adverse reactions. High-dose statin users experienced no remarkable transaminase elevation 0.00201 (95% CI [0.00004, 0.00398], = 33%). Creatine phosphokinase (CK) elevation under three times the upper limit was rare with a rate of 0.0043 (95% CI [0.0011, 0.0075], = 27%). Myalgia rates were comparable between high- and moderate-dose statins ( = 0.23). Gastrointestinal symptoms were infrequent with a rate of about 0.02 (95% CI [0.00, 0.01], = 52%). For patients with coronary heart disease, pravastatin 40 mg resulted in fewer transaminase elevations ( < 0.01). There is no difference in myalgia rates between moderate- and high-dose statins ( = 0.78). The proportion of myopathy was higher with simvastatin 80 mg compared to other statins. The risk of rhabdomyolysis was dose-dependent ( < 0.01). For heart failure patients, elderly patients showed varying risks of CK elevation, gastrointestinal symptoms, and muscle symptoms ( = 71%, 99%, and 99%, respectively). For patients with acute coronary syndrome or acute stroke, the rates of transaminase elevation were higher with simvastatin 40 mg and atorvastatin 80 mg compared to other statins ( < 0.01). There is no difference in myalgia rates between rosuvastatin 20 mg and atorvastatin 80 mg ( = 0.20). However, the rate of myalgia with atorvastatin 80 mg was higher than that of rosuvastatin 10 mg and atorvastatin 20 mg ( < 0.01). For diabetic patients, there was no difference in the effect on transaminases among four statin medications: rosuvastatin 10 and 40 mg, simvastatin 40 mg, and atorvastatin 80 mg (0.00058, 95% CI [0.00000, 0.00464], = 0%). Additionally, there was no difference in the rates of myalgia among atorvastatin 10, 40, and 80 mg and rosuvastatin 20 and 40 mg ( = 0.05). Statins' adverse reactions differ across populations. For those with hypercholesterolemia and diabetes, statins' impact on transaminase levels is similar. Yet patients with coronary heart disease, acute coronary syndrome, or acute stroke show varying responses. Notably, myalgia risk in hypercholesterolemia and coronary disease patients using different statins is comparable, but those with acute coronary syndrome or stroke, especially on high-dose rosuvastatin, have a higher myalgia risk.
在临床实践中,患者常因不良反应或不依从性而避免使用或停止使用他汀类药物。为阐明他汀类药物的不良反应、其在不同疾病中的变异性以及影响这些反应的因素,我们进行了一项基于高质量临床试验的荟萃分析。纳入了涉及他汀类药物且在以下三个数据库(PubMed、Embase和Cochrane图书馆)中详细记录不良反应的临床随机对照试验。检索工作于2024年1月31日完成。所有研究将使用ROB2量表进行偏倚风险评估。我们总共纳入了41项研究,涉及64,728名个体的总体样本量。在高脂血症患者中,四种他汀类药物的总不良事件总体发生率无差异( = 0.37)。辛伐他汀40毫克的他汀类药物相关不良反应较少。高剂量他汀类药物使用者的转氨酶升高情况不显著,为0.00201(95%置信区间[0.00004, 0.00398], = 33%)。肌酸磷酸激酶(CK)升高至上限三倍以下的情况罕见,发生率为0.0043(95%置信区间[0.0011, 0.0075], = 27%)。高剂量和中等剂量他汀类药物的肌痛发生率相当( = 0.23)。胃肠道症状不常见,发生率约为0.02(95%置信区间[0.00, 0.01], = 52%)。对于冠心病患者,普伐他汀40毫克导致的转氨酶升高较少( < 0.01)。中等剂量和高剂量他汀类药物的肌痛发生率无差异( = 0.78)。与其他他汀类药物相比,辛伐他汀80毫克的肌病比例更高。横纹肌溶解的风险呈剂量依赖性( < 0.01)。对于心力衰竭患者,老年患者出现CK升高、胃肠道症状和肌肉症状的风险各不相同(分别为 = 71%、99%和99%)。对于急性冠状动脉综合征或急性中风患者,与其他他汀类药物相比,辛伐他汀40毫克和阿托伐他汀80毫克的转氨酶升高率更高( < 0.01)。瑞舒伐他汀20毫克和阿托伐他汀80毫克的肌痛发生率无差异( = 0.20)。然而,阿托伐他汀80毫克的肌痛发生率高于瑞舒伐他汀10毫克和阿托伐他汀20毫克( < 0.01)。对于糖尿病患者,四种他汀类药物(瑞舒伐他汀10毫克和40毫克、辛伐他汀40毫克、阿托伐他汀80毫克)对转氨酶的影响无差异(0.00058,95%置信区间[0.00000, 0.00464], = 0%)。此外,阿托伐他汀10毫克、40毫克和80毫克以及瑞舒伐他汀20毫克和40毫克的肌痛发生率无差异( = 0.05)。他汀类药物的不良反应在不同人群中存在差异。对于高胆固醇血症和糖尿病患者,他汀类药物对转氨酶水平的影响相似。然而,冠心病、急性冠状动脉综合征或急性中风患者的反应各不相同。值得注意的是,高胆固醇血症和冠心病患者使用不同他汀类药物时的肌痛风险相当,但急性冠状动脉综合征或中风患者,尤其是使用高剂量瑞舒伐他汀的患者,肌痛风险更高。