Side Effects of Statins
Statins are generally safe and well-tolerated medications, but they can cause muscle-related symptoms (the most common side effect), modest increases in diabetes risk, and rarely, liver enzyme elevations—though the cardiovascular benefits far outweigh these risks in appropriate patients. 1
Most Common Side Effects
Muscle-Related Symptoms (Statin-Associated Muscle Symptoms - SAMS)
Muscle symptoms are the most frequent side effect, occurring in 1-5% of patients in clinical trials but 5-20% in real-world practice. 1
- Myalgia (muscle pain/aches) is the most common presentation, typically bilateral, involving proximal muscles, with normal creatine kinase (CK) levels 1
- Symptoms usually begin within weeks to months after starting therapy and resolve after discontinuation 1
- Myositis/myopathy (elevated CK with concerning symptoms or objective weakness) is rare 1
- Rhabdomyolysis (CK >10 times upper limit of normal with renal injury) is exceedingly rare and typically occurs only with multiple predisposing factors 1
- Statin-associated autoimmune myopathy (with HMGCR antibodies and incomplete resolution) is rare 1
Risk Factors for Muscle Symptoms:
- Advanced age (especially >80 years), with women at higher risk than men 1, 2
- Small body frame and frailty 2
- Low body mass index 1
- Multisystem disease (particularly chronic renal insufficiency from diabetes) 1, 2
- Polypharmacy and drug interactions (CYP3A4 inhibitors, OATP1B1 inhibitors, cyclosporine, gemfibrozil, macrolide antibiotics, antifungal agents) 1, 2
- Asian ancestry 1
- Excess alcohol consumption 1
- High levels of physical activity and trauma 1
- Perioperative periods 2
- Higher statin doses 2
New-Onset Diabetes Mellitus
Statins modestly increase the risk of developing type 2 diabetes in susceptible individuals, but this should NOT be cause for discontinuation. 1
- Risk is higher in patients with pre-existing diabetes risk factors: BMI ≥30, fasting glucose ≥100 mg/dL, metabolic syndrome, or HbA1c ≥6% 1
- Continue statin therapy if diabetes develops, with added emphasis on adherence, moderate-intensity physical activity, healthy dietary patterns, and modest weight loss 1
Liver-Related Effects
- Transaminase elevation (>3 times upper limit of normal) is infrequent 1
- Hepatic failure is rare 1
- Statins can be used in patients with chronic, stable liver disease (including non-alcoholic fatty liver disease) after obtaining baseline measurements and establishing monitoring schedules 1
Less Common or Unproven Side Effects
Gastrointestinal Symptoms
- Headache and dyspepsia occur but are generally mild 1
Neurological Effects
- Peripheral neuropathy is rare, with risk increasing with higher doses and longer duration (>1 year) 3
- Memory/cognition concerns are rare and not supported by large-scale randomized trials 1
Other Effects with No Definite Association
The following have been raised as concerns but are unfounded or not definitively associated with statin use: 1
- Cancer
- Renal dysfunction (recent data suggest possible protective effects)
- Cataracts
- Tendon rupture
- Hemorrhagic stroke
- Interstitial lung disease
- Low testosterone
Monitoring Recommendations
What TO Monitor:
- Evaluate muscle symptoms at baseline, 6-12 weeks after starting therapy, and at each follow-up visit 1
- Measure CK levels only in patients with severe muscle symptoms or objective muscle weakness—NOT routinely 1
- Measure liver transaminases (ALT/AST) initially, at approximately 12 weeks, then annually or if symptoms suggest hepatotoxicity 1
- Measure hepatic panel (including total bilirubin and alkaline phosphatase) if symptoms suggest hepatotoxicity 1
What NOT to Monitor:
- Routine CK and transaminase measurements are NOT useful in asymptomatic patients 1
Management of Side Effects
For Muscle Symptoms:
Use a "reassess, rediscuss, and rechallenge" approach—the majority of patients can successfully tolerate at least one statin with this strategy. 1
- Discontinue the statin until symptoms improve 1, 2
- Rechallenge with a reduced dose, alternative agent, or alternative dosing regimen (including alternate-day dosing) 1, 2
- Consider pravastatin as first choice for high-risk patients due to lower risk of drug interactions 2
- Use lower doses of more potent statins (e.g., rosuvastatin at lower doses) if higher potency is needed 2
- Avoid high-dose simvastatin due to higher myopathy risk, especially with drug interactions 2
- Consider combination therapy with ezetimibe and low-dose statin for patients who cannot tolerate standard doses 2
For Diabetes Risk:
- Continue statin therapy with lifestyle modifications (physical activity, healthy diet, weight loss) 1
For Peripheral Neuropathy:
- Consider dose reduction or temporary discontinuation 3
- Evaluate for other causes, particularly in diabetic patients 3
- Reinstitute therapy based on symptom resolution and risk-benefit assessment 3
Special Populations
Asian Patients:
- Approximately 2-fold increase in rosuvastatin exposure compared to White patients 4
- Adjust dosage accordingly 4
Severe Renal Impairment:
- Rosuvastatin exposure increases significantly in patients with CrCl <30 mL/min/1.73 m² not on hemodialysis 4
- Start with 5 mg daily and do not exceed 10 mg daily 4
- Renal impairment is a risk factor for myopathy and rhabdomyolysis 4
Hepatic Impairment:
- Contraindicated in acute liver failure or decompensated cirrhosis 4
- Chronic alcohol liver disease increases rosuvastatin exposure 4
Key Clinical Pitfalls to Avoid
- Do NOT routinely measure CK or liver enzymes in asymptomatic patients—this leads to unnecessary discontinuation 1
- Do NOT discontinue statins if diabetes develops—continue with lifestyle modifications 1
- Do NOT attribute all muscle symptoms to statins without evaluating other causes, as musculoskeletal symptoms are common in the general population 1
- Do NOT use coenzyme Q10 for routine prevention or treatment of muscle symptoms—it is not recommended 1
- Do NOT avoid statins in patients with stable liver disease—they can be used safely with appropriate monitoring 1