What statins (HMG-CoA reductase inhibitors) are used for stroke (cerebrovascular accident, CVA) prevention?

Statins for Stroke (CVA) Prevention

High-dose atorvastatin (80 mg daily) is the primary statin indicated for prevention of ischemic stroke recurrence, with a target LDL-C of <70 mg/dL for patients with atherosclerotic disease. 1

Indications for Statin Therapy in Stroke Prevention

• Statins should be initiated in all patients with established atherosclerotic disease and in patients at high risk for developing cardiovascular disease (CVD) for primary stroke prevention 1
• After a cerebrovascular event, statins should be started in patients with a history of non-cardioembolic ischemic stroke or transient ischemic attack (TIA) for prevention of further cardiovascular events 1
• Statins should be avoided following hemorrhagic stroke unless there is evidence of atherosclerotic disease or high CVD risk 1

Specific Statin Recommendations for Stroke Prevention

• Atorvastatin 80 mg daily is indicated for patients with ischemic stroke with no known coronary heart disease, no major cardiac sources of embolism, and LDL-C >100 mg/dL to reduce risk of stroke recurrence 1, 2
• In patients with ischemic stroke or TIA and atherosclerotic disease, lipid-lowering therapy with a statin and ezetimibe (if needed) to a goal LDL-C of <70 mg/dL is recommended 1, 2
• Rosuvastatin is indicated to reduce the risk of stroke in adults without established coronary heart disease who are at increased risk of CV disease 3

Efficacy of Statins in Stroke Prevention

• The SPARCL trial demonstrated that high-dose atorvastatin reduced stroke recurrence by 16% compared to placebo over 4.9 years 1, 4
• The 5-year absolute risk reduction for major cardiovascular events was 3.5% with atorvastatin (HR, 0.80; 95% CI, 0.69 to 0.92; p=0.002) 1, 4
• Treating 258 patients with atorvastatin 80mg daily for one year would prevent one recurrent stroke 4
• Greater LDL-C reduction correlates with improved outcomes, with patients achieving ≥50% reduction in LDL-C having a 35% reduction in combined risk of fatal and nonfatal stroke 4

Safety Considerations

• There was a higher incidence of hemorrhagic stroke in the atorvastatin treatment arm in SPARCL (2.3% vs 1.4% for placebo; HR, 1.66; 95% CI, 1.08 to 2.55) 1, 5
• Risk factors for hemorrhagic stroke with atorvastatin include:
  • Previous hemorrhagic stroke (HR, 5.65; 95% CI, 2.82 to 11.30) 4
  • Male sex (HR, 1.79; 95% CI, 1.13 to 2.84) 5, 4
  • Advanced age (HR, 1.42 per 10-year increment; 95% CI, 1.16 to 1.74) 5, 4
  • Stage 2 hypertension 5, 4
• Statin therapy is generally well tolerated, with a mildly increased rate of elevated liver enzymes and creatine kinase 1
• 5-10% of patients receiving statins develop myopathy, but rhabdomyolysis is extremely rare 1

Monitoring Recommendations

• Check lipid levels 4-12 weeks after initiating statin therapy and every 3-12 months thereafter to assess adherence and efficacy 1, 2
• For patients who experienced an acute coronary syndrome, blood lipids should be checked 4-6 weeks after the event to determine whether the target level has been reached 1

Algorithm for Statin Use in Stroke Prevention

1. For primary prevention: Initiate statins in patients at high risk for developing CVD 1
2. For secondary prevention after ischemic stroke/TIA:
   • Start atorvastatin 80 mg daily for patients with LDL-C >100 mg/dL 1, 2
   • Target LDL-C <70 mg/dL for patients with atherosclerotic disease 1, 2
   • If target LDL-C is not achieved with maximum tolerated statin, add ezetimibe 1, 2
   • For very high-risk patients still not at goal, consider a PCSK9 inhibitor 1
3. After hemorrhagic stroke: Avoid statins unless there is evidence of atherosclerotic disease or high CVD risk 1

Drug Interactions and Precautions

• The risk of myopathy can be increased when statins are used concomitantly with:
  • Cyclosporin, tacrolimus
  • Macrolides (azithromycin, clarithromycin, erythromycin)
  • Azole antifungals (itraconazole, ketoconazole, fluconazole)
  • Calcium antagonists (mibefradil, diltiazem, verapamil)
  • HIV protease inhibitors
  • Other drugs including digoxin, niacin, and fibrates (particularly gemfibrozil) 1