Background & Aims: The risk reduction of major vascular events per 1.0 mmol/L further reduction in LDL-cholesterol did not depend on the baseline LDL-cholesterol concentration. However, the desirable LDL-cholesterol level for preventing stroke recurrence has still not been defined. To define desirable LDL-cholesterol levels for preventing stroke recurrence, subanalysis was made on J-STARS.
Methods: In J-STARS, patients with non-cardioembolic ischemic stroke (atherothrombotic infarction, lacunar infarction, infarction of undetermined etiology) were randomized into the pravastatin group (10 mg/day, n=793) or the control group (n=785) received no statin treatment. The primary endpoint was the recurrence of stroke and transient ischemic attack (TIA). The subjects were divided based on tertile of LDL-cholesterol at enrollment, mean during observation period, just before the event, and their differences. Adjusted hazard ratio (HR) (95% confidence interval [CI]) were analyzed for each tertile adjusting the factors that showed inter-group differences, including age, body mass index, hypertension, diabetes mellitus, duration until an enrollment following stroke events, and the usage of statin. Reference was set at the highest tertile.
Results: Adjusted HR of stroke and TIA lowered in accordance with the reduction of LDL-cholesterol from enrollment both to mean during observation period and to just before the event (p<0.001 and <0.001 for trend). The occurrence of intracranial hemorrhage showed a significantly low relative risk in the middle tertile of LDL-cholesterol reduction (2.0 to 28.0 mg/dl) from enrollment to just before the event (adjusted HR 0.15 [95%CI 0.03, 0.68]). But, this risk reduction of intracranial hemorrhage was diminished in the lowest tertile. And, a relatively high risk of intracranial hemorrhage was observed in the lowest tertile of LDL-cholesterol (less than 101.0 mg/dl) just before the event (2.68 [0.82, 8.77]).
Conclusions: The composite risk of stroke and TIA reduced according to the reduction of LDL-cholesterol adjusting the statin usage. The risk of intracranial hemorrhage reduced with mild reduction of LDL-cholesterol, but not when LDL-cholesterol reduced more than 28.0 mg/dl. (NCT00221104)