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

Int J Stroke. 2012 Feb;7(2):104-11. doi: 10.1111/j.1747-4949.2011.00653.x. Epub 2011 Nov 2.

Abstract

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 53 ± 22 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) mm² at day 3, compared with 398 (144, 2053) mm² among the placebo group, P= 0.79 controlling for baseline values; and 822 (159, 1717) mm² at day 30, cf 280 (76, 1330) mm²; P=0.63); or atorvastatin (454 (107, 1765) mm² cf 825 (265, 2509) mm² at day 3; P= 0.33; and 462 (43, 1399) mm² cf 280 (128, 1559) mm² at day 30, P= 0.79). 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= 0.048); 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= 0.01)) and in the unaffected hemisphere (- 7.3 mL/100 mL/min (95% CI: - 1.3, -13.4; P= 0.02)). Atorvastatin therapy was well tolerated, but irbesartan therapy was associated with an increased rate of withdrawal from therapy (n=10 (29%), compared with n=3 (9%) who withdrew from placebo, P= 0.04).

Conclusions: Treatment with atorvastatin and irbesartan, initiated on day 3 after acute ischemic stroke, did not appear to substantially modify infarct growth.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angiotensin II Type 1 Receptor Blockers / adverse effects
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Atorvastatin
  • Biphenyl Compounds / adverse effects
  • Biphenyl Compounds / therapeutic use*
  • Brain Ischemia / complications
  • Brain Ischemia / drug therapy*
  • Cerebral Infarction / pathology
  • Disease Progression
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Heptanoic Acids / adverse effects
  • Heptanoic Acids / therapeutic use*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Irbesartan
  • Male
  • Middle Aged
  • Monitoring, Physiologic
  • Pyrroles / adverse effects
  • Pyrroles / therapeutic use*
  • Sample Size
  • Stroke / drug therapy*
  • Stroke / etiology
  • Tetrazoles / adverse effects
  • Tetrazoles / therapeutic use*
  • Tomography, X-Ray Computed
  • Treatment Outcome

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Biphenyl Compounds
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • Tetrazoles
  • Atorvastatin
  • Irbesartan