Hemorrhagic stroke in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels study

Background: In the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) study, atorvastatin 80 mg/day reduced the risk of stroke in patients with recent stroke or TIA. Post hoc analysis found this overall benefit included an increase in the numbers of treated patients having hemorrhagic stroke (n = 55 for active treatment vs n = 33 for placebo). Methods: We explored the relationships between hemorrhage risk and treatment, baseline patient characteristics, most recent blood pressure, and most recent low-density lipoprotein (LDL) cholesterol levels prior to the hemorrhage. Results: Of 4,731 patients, 67% had ischemic strokes, 31% TIAs, and 2% hemorrhagic strokes as entry events. In addition to atorvastatin treatment (HR 1.68, 95% CI 1.09 to 2.59, p = 0.02), Cox multivariable regression including baseline variables significant in univariable analyses showed that hemorrhagic stroke risk was higher in those having a hemorrhagic stroke as the entry event (HR 5.65, 95% CI 2.82 to 11.30, p < 0.001), in men (HR 1.79, 95% CI 1.13 to 2.84, p = 0.01), and with age (10y increments, HR 1.42, 95% CI 1.16 to 1.74, p = 0.001). There were no statistical interactions between these factors and treatment. Multivariable analyses also found that having Stage 2 (JNC-7) hypertension at the last study visit before a hemorrhagic stroke increased risk (HR 6.19, 95% CI 1.47 to 26.11, p = 0.01), but there was no effect of most recent LDL-cholesterol level in those treated with atorvastatin. Conclusions: Hemorrhagic stroke was more frequent in those treated with atorvastatin, in those with a hemorrhagic stroke as an entry event, in men, and increased with age. Those with Stage 2 hypertension at the last visit prior to the hemorrhagic stroke were also at increased risk. Treatment did not disproportionately affect the hemorrhagic stroke risk associated with these other factors. There were no relationships between hemorrhage risk and baseline low-density lipoprotein (LDL) cholesterol level or recent LDL cholesterol level in treated patients.