Is Lipitor (atorvastatin) or Crestor (rosuvastatin) more likely to cause musculoskeletal pain (myalgia)?

Lipitor vs Crestor: Comparative Risk of Musculoskeletal Pain

There is no clinically meaningful difference in the risk of muscle pain between Lipitor (atorvastatin) and Crestor (rosuvastatin)—both statins carry equivalent risk for myalgia and severe myopathy. 1, 2

Evidence Supporting Equivalent Risk

The FDA conducted a comprehensive analysis of fatal rhabdomyolysis rates across all marketed statins and found no clinically important differences among atorvastatin, rosuvastatin, and other currently available statins, with rates considered equivalent at less than 1 death per million prescriptions. 1 The 2019 ACC/AHA cholesterol guidelines explicitly state that myalgias occur at comparable frequencies across all statins in both randomized controlled trials (1-5%) and observational studies (5-10%). 1

All currently marketed statins have similar potential for causing severe myopathy, with rates considered equivalent by regulatory authorities. 1, 2

Critical Context: Most Muscle Pain Is Not Actually Statin-Related

A systematic analysis of 26 randomized trials found myalgia incidence of 12.7% in statin groups versus 12.4% in placebo groups (p=0.06), demonstrating that most muscle complaints occur at similar rates regardless of statin exposure. 2 However, one blinded controlled trial (STOMP) specifically with atorvastatin 80 mg confirmed that statins do increase muscle complaints compared to placebo (19 versus 10 subjects, P=0.05), though without decreasing muscle strength or exercise performance. 3

Real-world observational data shows higher rates than clinical trials: approximately 10% of statin-treated patients report muscular symptoms in practice settings, with 30% of symptomatic patients discontinuing therapy. 4

Risk Factors That Matter More Than Statin Choice

The following patient characteristics increase myalgia risk far more than the specific statin selected: 1, 2, 5

• Advanced age (especially >80 years), with women at higher risk than men
• Small body frame and frailty
• Chronic renal insufficiency (particularly from diabetes)
• Polypharmacy and drug-drug interactions (CYP3A4 inhibitors, gemfibrozil, macrolide antibiotics, antifungal agents)
• Hypothyroidism or vitamin D deficiency
• Higher statin doses

Practical Management Algorithm

If Starting Therapy in High-Risk Patients:

For patients with multiple risk factors for myalgia, start with pravastatin due to its hydrophilic nature and lower risk of drug interactions, not because atorvastatin or rosuvastatin are inherently more myalgic. 2, 5 If higher potency is needed, rosuvastatin can be effective at lower doses (5-10 mg) rather than using higher doses of less potent statins. 2, 5

If Myalgia Develops on Either Atorvastatin or Rosuvastatin:

1. Temporarily discontinue the statin until symptoms resolve completely (typically 2-4 weeks). 1, 6

2. Rule out other causes: Check CK, TSH, vitamin D, renal/hepatic function, and review for drug interactions. 6, 5

3. Rechallenge with the same statin at lower dose OR switch to an alternative statin with different metabolic properties: 6

   • Pitavastatin (minimal CYP3A4 dependence, superior tolerability data)
   • Pravastatin (hydrophilic, non-CYP3A4 dependent)
   • Rosuvastatin if coming from atorvastatin, or vice versa (both hydrophilic but different metabolism)
   • Fluvastatin (lower muscle-related adverse events)

4. 92.2% of initially intolerant patients can successfully tolerate rechallenge with an alternative strategy. 2, 6

Common Pitfalls to Avoid

Do not abandon statin therapy after a single episode of myalgia without proper rechallenge. The ACC/AHA guidelines emphasize a "reassess, rediscuss, and rechallenge" approach, as most patients can tolerate an alternative regimen. 1, 2 Only after failing at least 2-3 different statins (including one at the lowest approved dose) should you consider the patient truly statin-intolerant. 6

Do not attribute pre-existing musculoskeletal symptoms to the statin. Document baseline muscle symptoms before initiating therapy, as musculoskeletal complaints are common in the general adult population. 1, 2

Do not use ezetimibe monotherapy as a first alternative. Combining ezetimibe 10 mg with a maximally tolerated low-dose statin is superior to either drug alone and provides better cardiovascular outcomes than ezetimibe monotherapy. 6

Alternative Dosing Strategies

If standard daily dosing fails with multiple statins, consider alternate-day dosing with long half-life statins (atorvastatin or rosuvastatin at lowest doses), which may reduce myalgia risk while maintaining efficacy. 2, 6