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Statin Therapy and Outcome After Ischemic Stroke Systematic Review and Meta-Analysis of Observational Studies and Randomized Trials

Journal

STROKE
Volume 44, Issue 2, Pages 448-456

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/STROKEAHA.112.668277

Keywords

cerebral infarction; ischemia; neuroprotective agents; outcomes assessment; stroke; therapy

Funding

  1. National Institutes of Health/NINDS [K23NS064052]
  2. National Health and Medical Research Council of Australia [438700]
  3. Irish Health Services Executive
  4. National Lottery of Ireland
  5. Servier
  6. Boehringer Ingelheim
  7. Pfizer Inc
  8. Sanofi-aventis
  9. Shire plc
  10. Kaethe-Zingg-Schwichtenberg-Fonds of the Swiss Academy of Medical Sciences
  11. Swiss Heart Foundation
  12. Swiss National Funds
  13. Health Research Board of Ireland
  14. Irish Heart Foundation
  15. Instituto de Salud Carlo III

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Background and Purpose-Although experimental data suggest that statin therapy may improve neurological outcome after acute cerebral ischemia, the results from clinical studies are conflicting. We performed a systematic review and meta-analysis investigating the relationship between statin therapy and outcome after ischemic stroke. Methods-The primary analysis investigated statin therapy at stroke onset (prestroke statin use) and good functional outcome (modified Rankin score 0 to 2) and death. Secondary analyses included the following: (1) acute poststroke statin therapy (<= 72 hours after stroke), and (2) thrombolysis-treated patients. Results-The primary analysis included 113 148 subjects (27 studies). Among observational studies, statin treatment at stroke onset was associated with good functional outcome at 90 days (pooled odds ratio [OR], 1.41; 95% confidence interval [CI], 1.29-1.56; P<0.001), but not 1 year (OR, 1.12; 95% CI, 0.9-1.4; P=0.31), and with reduced fatality at 90 days (pooled OR, 0.71; 95% CI, 0.62-0.82; P<0.001) and 1 year (OR, 0.80;95% CI, 0.67-0.95; P=0.01). In the single randomized controlled trial reporting 90-day functional outcome, statin treatment was associated with good outcome (OR, 1.5; 95% CI, 1.0-2.24; P=0.05). No reduction in fatality was observed on meta-analysis of data from 3 randomized controlled trials (P=0.9). In studies restricted to of thrombolysis-treated patients, an association between statins and increased fatality at 90 days was observed (pooled OR, 1.25; 95% CI, 1.02-1.52; P=0.03, 3 studies, 4339 patients). However, this association was no longer present after adjusting for age and stroke severity in the largest study (adjusted OR, 1.14; 95% CI, 0.90-1.44; 4012 patients). Conclusion-In the largest meta-analysis to date, statin therapy at stroke onset was associated with improved outcome, a finding not observed in studies restricted to thrombolysis-treated patients. Randomized trials of statin therapy in acute ischemic stroke are needed. (Stroke. 2013;44:448-456.)

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