A Meta-Analysis of the Incidence of Adverse Reactions of Statins in Various Diseases

Introduction: 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. Materials and Methods: 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. Results: 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 (p = 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], I ² = 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], I ² = 27%). Myalgia rates were comparable between high- and moderate-dose statins (p = 0.23). Gastrointestinal symptoms were infrequent with a rate of about 0.02 (95% CI [0.00, 0.01], I ² = 52%). For patients with coronary heart disease, pravastatin 40 mg resulted in fewer transaminase elevations (p < 0.01). There is no difference in myalgia rates between moderate- and high-dose statins (p = 0.78). The proportion of myopathy was higher with simvastatin 80 mg compared to other statins. The risk of rhabdomyolysis was dose-dependent (p < 0.01). For heart failure patients, elderly patients showed varying risks of CK elevation, gastrointestinal symptoms, and muscle symptoms (I ² = 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 (p < 0.01). There is no difference in myalgia rates between rosuvastatin 20 mg and atorvastatin 80 mg (p = 0.20). However, the rate of myalgia with atorvastatin 80 mg was higher than that of rosuvastatin 10 mg and atorvastatin 20 mg (p < 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], I ² = 0%). Additionally, there was no difference in the rates of myalgia among atorvastatin 10, 40, and 80 mg and rosuvastatin 20 and 40 mg (p = 0.05). Conclusion: 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.