Statin Therapy and Outcome After Ischemic Stroke

Abstract

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, 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. 5-12 Experimental and clinical data also provide some evidence that statins may have neuroprotective effects after acute cerebral ischemia. [7][8][9][10][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] In animal models, treatment with statins either before, or early after, cerebral arterial occlusion has been associated with reduced infarct volume and improved neurological function. [5][6][7][8][9][10]13,14 Data are conflicting regarding the relationship between acute statin therapy and outcome after human ischemic stroke. Some authors have reported improved survival and functional outcome associated with statin treatment, but these findings have not been consistently replicated. [15][16][17][18][19][20][21][22][23][24][25][26][27][28][31][32][33][34][35][36] Interpretations can be difficult because of limited sample sizes in some reports and possible bias in statin allocation in other studies, particularly those in which statins were allocated in a nonrandomized fashion. Some authors have also reported worse outcomes in patients treated with the combination of acute statins and intravenous thro...

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