Which Statin Causes the Least Myopathy?
All currently marketed statins (atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin, and rosuvastatin) have clinically equivalent rates of severe myopathy and should be considered to have similar myopathy risk, with the notable exception that cerivastatin (now withdrawn) had dramatically higher rates. 1
Evidence from FDA Analysis and Guidelines
The ACC/AHA/NHLBI performed a comprehensive analysis of FDA adverse event data and concluded that there are no clinically important differences in the rate of fatal rhabdomyolysis among the five statins available (atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin), with all showing rates of severe myopathy around 0.08-0.09%. 1 The guideline explicitly states that "clinicians should consider the rates of severe myopathy as equivalent among all of these approved statins." 1
Practical Approaches for Patients with Prior Myopathy
Despite the equivalent severe myopathy rates, when patients develop muscle symptoms on one statin, switching to pravastatin or fluvastatin is recommended due to fewer drug interactions and potentially better tolerability in clinical practice. 2 These statins have less interaction with the cytochrome P-450 system, which may reduce risk in patients taking multiple medications. 2
Alternative Dosing Strategies
- Once-weekly rosuvastatin can be considered as an alternative dosing strategy to reduce myopathy risk while maintaining some LDL-C reduction. 2
- Lower doses of any statin should be used, as myopathy risk is dose-dependent. 2
- Pitavastatin showed promising tolerability in a case report where a patient failed fluvastatin, pravastatin, and atorvastatin, though this is limited evidence. 3
Key Risk Factors to Address
Before attributing symptoms to the statin itself, evaluate for:
- Advanced age (especially >80 years), female gender, small body frame, frailty 2
- Chronic renal insufficiency and multisystem disease 2
- Hypothyroidism (check TSH) 2
- Drug interactions with cytochrome P-450 inhibitors, gemfibrozil, cyclosporine, or macrolide antibiotics 2
- Perioperative periods 2
Important Caveats
While observational data suggest myalgia may occur in up to 10% of statin users, the rate of life-threatening rhabdomyolysis remains extremely rare (less than 1 death per million prescriptions) across all statins. 1 The distinction between subjective muscle complaints and objective myopathy with CK elevation is critical, as many muscle symptoms occur at similar rates in placebo groups. 1
The only proven effective treatment for confirmed statin-induced myopathy is discontinuation or dose reduction, followed by rechallenge with a different statin at lower doses. 4