Should statins (HMG-CoA reductase inhibitors) be given to patients with intracerebral hemorrhage?

Statin Use in Patients with Intracerebral Hemorrhage

In patients with spontaneous intracerebral hemorrhage (ICH) and an established indication for statin therapy, the risks and benefits of statin therapy on ICH outcomes and recurrence relative to overall prevention of cardiovascular events are uncertain, and statins should generally be avoided following ICH, particularly in cases with lobar location. 1

Risk Assessment for Statin Use After ICH

• The 2022 American Heart Association/American Stroke Association guideline states that in patients with spontaneous ICH who have an established indication for statin therapy, the risks and benefits on ICH outcomes and recurrence relative to overall prevention of cardiovascular events are uncertain (Class 2b, Level of Evidence B-NR) 1

• Risk factors that should be considered when evaluating statin use after ICH include:

  • Lobar location of the initial ICH (higher risk of recurrence) 1
  • Older age 1
  • Presence and number of microbleeds on gradient echo MRI 1
  • Presence of apolipoprotein E ε2 or ε4 alleles 1

• Post-hoc analysis of the SPARCL trial identified that patients with hemorrhagic stroke as the qualifying event had the highest risk of recurrent hemorrhagic stroke when treated with high-dose atorvastatin 1, 2

Evidence for Avoiding Statins After ICH

• A decision analysis study found that avoiding statins should be considered for patients with a history of ICH, particularly those with lobar location 3

• In survivors of lobar ICH without prior cardiovascular events, avoiding statins yielded a life expectancy gain of 2.2 quality-adjusted life-years compared with statin use 3

• The 2015 Canadian Stroke Best Practice Recommendations state that statin therapy is not indicated for prevention of ICH 1

• For ICH patients who have a clear concomitant indication for cholesterol-lowering treatment, statin therapy should be individualized and should take into account the patient's overall thrombotic risk as well as the possibility of increased risk of ICH on statin therapy 1

Evidence Supporting Statin Use After ICH

• A large Danish population-based study found no evidence that statins increase the risk of recurrent ICH in individuals with prior ICH, and may even lower the risk in those with prior ischemic stroke 4

• Early statin therapy in patients with acute ICH without prior statin use was not associated with increased risk of recurrent ICH and might be associated with lower all-cause mortality during follow-up 5

• Early continuation of statin therapy after ICH has been associated with favorable functional outcome at 90 days 6

Clinical Decision Algorithm

1. For patients with lobar ICH:

   • Generally avoid statin therapy unless there is a compelling indication for cardiovascular risk reduction 3, 2
   • If the patient has had prior cardiovascular events, the annual recurrence risk of myocardial infarction would need to exceed 90% to favor statin therapy 3

2. For patients with deep (non-lobar) ICH:

   • Consider avoiding statins, although the margin of benefit is smaller than for lobar ICH 3
   • If there is a strong indication for statin therapy (e.g., established atherosclerotic disease), carefully weigh risks and benefits 2, 7

3. For all ICH patients on statin therapy:

   • Ensure strict blood pressure control with a long-term goal of BP <130 mm Hg systolic and 80 mm Hg diastolic 1
   • Avoid concomitant medications that increase bleeding risk when possible, such as NSAIDs 1
   • Consider lifestyle modifications including avoidance of alcohol use greater than 2 drinks per day, tobacco use, and illicit drug use 1

Common Pitfalls and Caveats

• Discontinuing statins in patients with high cardiovascular risk may increase their risk of ischemic events 7

• The evidence regarding statin use after ICH is conflicting, with some studies showing potential benefit and others suggesting harm 1, 8

• Regular monitoring of lipid levels and assessment of cardiovascular risk factors should be performed in all ICH patients, regardless of statin use 7

• The decision to use statins after ICH should consider the specific type of ICH (lobar vs. deep), the patient's cardiovascular risk profile, and the potential for recurrent ICH 2, 3