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

source extracted confidence: high 2026-04-09
#hydroxymethylglutaryl-coa-reductase-inhibitors #humans #randomized-controlled-trials-as-topic #muscular-diseases #double-blind-method

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

Hou et al., 2024 | Cardiovasc Drugs Ther | Systematic Review

Citation

Hou Qingtao, Chen Yuqin, ... Pang Caishuang. Comparative Muscle Tolerability of Different Types and Intensities of Statins: A Network Meta-Analysis of Double-Blind Randomized Controlled Trials. Cardiovasc Drugs Ther. 2024-Jun;38(3):459-469. 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.

Key Findings

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 event

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population See abstract
Sample Size 83
Age Range See abstract
Condition See abstract

MeSH Terms

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Humans
  • Randomized Controlled Trials as Topic
  • Muscular Diseases
  • Double-Blind Method
  • Atorvastatin
  • Muscle, Skeletal
  • Myalgia
  • Rhabdomyolysis

Evidence Classification

  • Level: Systematic Review
  • Publication Types: Journal Article, Systematic Review, Comparative Study, Network Meta-Analysis
  • Vertical: creatine

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09