Comparative Muscle Tolerability of Different Types and Intensities of Statins: A Network Meta-Analysis of Double-Blind Randomized Controlled Trials

Qingtao Hou; Yuqin Chen; Yingxiao Zhang; Caishuang Pang

doi:10.1007/s10557-022-07405-0

Comparative Muscle Tolerability of Different Types and Intensities of Statins: A Network Meta-Analysis of Double-Blind Randomized Controlled Trials

Cardiovasc Drugs Ther. 2022 Nov 30. doi: 10.1007/s10557-022-07405-0. Online ahead of print.

Authors

Qingtao Hou¹, Yuqin Chen², Yingxiao Zhang³, Caishuang Pang⁴

Affiliations

¹ Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, 1# Youyi Road, Yuzhong District, Chongqing, 400016, People's Republic of China. 510766475@qq.com.
² Neuroscience Research Center, College of Basic Medicine, Chongqing Medical University, Chongqing, 400016, People's Republic of China.
³ Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, 1# Youyi Road, Yuzhong District, Chongqing, 400016, People's Republic of China.
⁴ Chongqing Medical University, Chongqing, 400016, People's Republic of China.

PMID: 36447018
DOI: 10.1007/s10557-022-07405-0

Abstract

Purpose: The benefits of statins for ischemic cardio-cerebrovascular diseases are well known. However, concerns around muscle adverse events still exist. We therefore aimed to compare the muscle safety of individual statins in adults.

Methods: PubMed, Embase, Cochrane Central Register of Controlled Trials and Web of Science were searched to include double-blind randomized controlled trials (RCTs) comparing one statin with another or with control treatment. Pairwise meta-analyses and network meta-analyses were undertaken with Stata 14.0 software. Relative risk (RR) with 95% confidence intervals (CIs) was adopted for each outcome.

Results: A total of 83 RCTs were included. In the pairwise meta-analysis, statins were significantly associated with only a slight increase in muscle symptoms compared with control (RR=1.05; 95% CI=1.01-1.09). In the drug-level network meta-analyses, no statistically significant difference was found between individual statins in the incidence of muscle symptoms, myalgia, myopathy, rhabdomyolysis, creatine kinase (CK) >10 times the upper limit of normal (ULN) or discontinuation due to muscle adverse events. In the dose-level network meta-analyses, there were no statistically significant dose-dependent effects on any outcomes except that moderate-intensity statins had a higher incidence of muscle symptoms than control (RR=1.13; 95% CI=1.01-1.27). Moderate simvastatin (RR=6.57; 95% CI=1.26-34.41) and moderate pravastatin (RR=5.96; 95% CI=1.00-35.44) had a statistically significantly higher incidence of CK >10×ULN compared with moderate atorvastatin. Lipophilic statins and statins metabolized by liver cytochrome P450 3A4 were not associated with an increased risk of muscle adverse events.

Conclusion: Statins may be generally safe on muscle. Moderate atorvastatin may be superior to equivalent simvastatin and pravastatin in muscle tolerability.

Keywords: Cytochrome P450 3A4; Lipophilicity; Muscle adverse events; Network meta-analysis; Randomized controlled trials; Statins.

Grants and funding

81901425/National Natural Science Foundation of China