A randomized placebo controlled trial of early treatment of acute ischemic stroke with atorvastatin and irbesartan

Background Cholesterol and blood pressure lowering therapies are effective in the secondary prevention of ischemic stroke. Aim To determine whether 30 days of treatment with atorvastatin, or irbesartan, initiated within 96 h of symptom onset improves recovery from acute ischemic stroke. Methods Eighty-one patients with acute ischemic stroke participated in this double-blind, placebo-controlled, randomized trial of atorvastatin (80 mg) vs. placebo, and/or irbesartan (150 mg) vs. placebo. Fifty-two patients (randomized 53722 h after onset of symptoms) completed the 30-day primary outcome follow-up. Results The primary outcome, maximal brain infarct size at days 3 and 30 measured by perfusion computed tomography, was not significantly altered by random assignment to irbesartan (1088 (IQR 216, 2594) mm(2) at day 3, compared with 398 (144, 2053) mm(2) among the placebo group, P=50.79 controlling for baseline values; and 822 (159, 1717) mm(2) at day 30, cf 280 (76, 1330) mm(2); P=50.63); or atorvastatin (454 (107, 1765) mm(2) cf 825 (265, 2509) mm(2) at day 3; P=50.33; and 462 (43, 1399) mm(2) cf 280 (128, 1559) mm(2) at day 30, P=50.79). There were no other significant differences among the treatment groups with the exception of: high sensitivity C-reactive protein concentrations, which were lower in the irbesartan treatment group at day 30 (mean difference 12.6 mg/L; 95% CI: -25.1, -0.1; P=50.048); and the mean cerebral blood flow in the affected cerebral hemisphere at 30 days after stroke, which was significantly reduced by random assignment to irbesartan compared with placebo in both the affected cerebral hemisphere (-7.5 mL/100 mL/min (95% CI: -1.7 to -13.4, P=50.01)) and in the unaffected hemisphere (-7.3 mL/100 mL/min (95% CI: -1.3, -13.4; P=50.02)). Atorvastatin therapywaswell tolerated, but irbesartan therapy was associated with an increased rate of withdrawal from therapy (n=510 (29%), compared with n=3 (9%) who withdrew from placebo, P=50.04). Conclusions Treatment with atorvastatin and irbesartan, initiated on day 3 after acute ischemic stroke, did not appear to substantially modify infarct growth.