Statin Use and Brain Hemorrhage

The relationship between statin use and intracerebral hemorrhage (ICH) has not been definitively established. Studies show both benefit and detriment. Statins may decrease the level of platelet aggregation and thrombogenesis and thus worsen an ICH, but they also modulate the immune system, inhibit the inflammatory process, and improve cerebral blood flow, promoting neuroprotection and tissue recovery. Despite physiological and clinical evidence on both sides of the argument, the idea that statins should be avoided whenever brain hemorrhage is involved has permeated stroke practice. Indeed, early and more recent epidemiological studies have shown a convincing inverse association between low levels of low-density lipoprotein cholesterol and the risk of hemorrhagic stroke. 1 Whether this association can be applied to patients treated with statins is less clear. Is the fear of statin use for ICH justified? What is the basis on which clinicians have come to avoid statins for their hemorrhage risk, and how should this information guide our practice in light of newer evidence? Part of the confusion arises from a lack of clarity of the association between statin use and hemorrhage under different ICH etiologies. The pathophysiology may be quite different if the brain hemorrhage occurs in the setting of ischemic stroke vs after thrombolytic therapy, in hypertensive ICH, or in other conditions such as amyloid angiopathy. In the last decade, 2 large randomized trials suggested an association between treatment with statins and increased risk of ICH in the setting of acute ischemic stroke. The 2004 Heart Protection Study, 2 a large multicenter, randomized trial of simvastatin 40 mg vs placebo for patients with dyslipidemia and cerebrovascular disease, coronary disease, some other occlusive coronary disease, diabetes mellitus, or treated hypertension showed a nonsignificant increase in the rate of hemorrhagic stroke (1.3% of patients who received 40 mg of simvastatin vs 0.7% of patients who received placebo) in the treatment arm of patients who had a prior cerebrovascular event. The 2008 Stroke Prevention by Aggressive Reduction in Cholesterol Levels trial 3 showed that hemorrhagic stroke was more frequent among those treated with atorvastatin calcium (unadjusted hazard ratio, 1.68 [95% CI, 1.09-2.69]) than among those who received placebo, although hemorrhagic stroke as an entry level event, male sex, and advanced age at baseline accounted for 86% of the increased risk of hemorrhage. Two additional clinical studies 4,5 have shown no evidence of increased