What is the role of rosuvastatin (statin) in patients with intracerebral hemorrhage (ICH)?

Rosuvastatin in Intracerebral Hemorrhage (ICH)

Rosuvastatin and other statins should generally be avoided in patients with intracerebral hemorrhage, particularly those with lobar ICH, unless there are compelling indications for statin therapy such as high cardiovascular risk or established atherosclerotic disease. 1, 2

Risk Assessment for Statin Use in ICH Patients

• The risk-benefit ratio of statin therapy should be carefully evaluated in patients with prior ICH, with special caution for those with lobar ICH 1
• Risk factors that increase the likelihood of ICH recurrence include: lobar location of initial ICH, older age, presence and number of microbleeds on gradient echo MRI, ongoing anticoagulation, and presence of apolipoprotein E ε2 or ε4 alleles 1
• The SPARCL study found that high-dose atorvastatin was associated with an increased risk of ICH, particularly in patients with ICH as their qualifying stroke event 1
• However, a meta-analysis of 31 randomized controlled trials including 91,588 statin-treated patients found no significant association between statin use and ICH (OR, 1.08; 95% CI, 0.88–1.32; P=0.47) 1

Evidence for Statin Use After ICH

• The American Heart Association/American Stroke Association guidelines state that there are insufficient data to recommend restrictions on the use of statins in ICH patients (Class IIb; Level of Evidence C) 1
• The European Society of Cardiology recommends avoiding statins following hemorrhagic stroke unless there is evidence of atherosclerotic disease or high cardiovascular disease risk 2
• A large Danish cohort study found no evidence that statins increase the risk of recurrent ICH in individuals with prior ICH, and may even reduce risk in those with prior ischemic stroke 3
• A small retrospective study found that statin pre-treatment was associated with better functional outcomes at 3 months in ICH patients (OR: 4.21; CI 1.47-12.17; P = 0.008) 4

Intensity of Statin Therapy in ICH Patients

• If statin therapy is deemed necessary in ICH patients, recent real-world evidence suggests that moderate-intensity statin therapy may be preferable to high-intensity therapy 5
• Moderate-intensity statin therapy was associated with lower risks of recurrent ICH (23.4% vs 24.9%; HR, 0.91; 95% CI, 0.86-0.97; p=0.002) compared to high-intensity therapy 5
• Moderate-intensity therapy also showed reductions in ischemic stroke (7.1% vs 10.2%; HR, 0.68; 95% CI, 0.59-0.78; p<0.001) and all-cause mortality (9.0% vs 10.2%; HR, 0.87; 95% CI, 0.79-0.96; p=0.004) 5

Management Recommendations

• For patients with ICH who have compelling indications for statin therapy (e.g., established atherosclerotic disease):

  • Consider using moderate-intensity statin therapy rather than high-intensity therapy 5
  • Ensure strict blood pressure control with a long-term goal of BP <130 mm Hg systolic and 80 mm Hg diastolic 1
  • Monitor for signs of recurrent hemorrhage 2

• For patients with lobar ICH without compelling cardiovascular indications:

  • Consider avoiding statin therapy due to potentially higher risk of recurrence 1, 2
  • If statin therapy is necessary, use the lowest effective dose to achieve treatment goals 5

• For all ICH patients, implement additional preventive measures:

  • Strict blood pressure control (target <130/80 mmHg) 1
  • Lifestyle modifications including limiting alcohol consumption, smoking cessation, and treatment of obstructive sleep apnea 1
  • Avoid long-term anticoagulation with warfarin for nonvalvular atrial fibrillation after lobar ICH 1

Specific Considerations for Rosuvastatin

• There is limited data specifically on rosuvastatin in ICH patients
• In acute ischemic stroke, rosuvastatin 20mg was found to reduce hemorrhagic transformation compared to placebo (4.4% vs 14.5%, P=0.007) 6
• If rosuvastatin is used in patients with prior ICH, moderate-intensity dosing (5-10 mg) may be preferable to high-intensity dosing (20-40 mg) based on general statin safety data in ICH 5