Level 1: Likely reliable evidence

The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial evaluated the effect of atorvastatin (Lipitor) 80 mg once daily on risk of stroke. The subjects were 4,731 functionally independent patients who had a stroke or transient ischemic attack (TIA) within the previous one to six months, an LDL of 100-190 mg/dL, and no known coronary artery disease (N Engl J Med. 2006;355:549-559). The median follow-up was 4.9 years. Follow-up was achieved for 96% of atorvastatin vs. 95% of placebo patients; all randomized patients were analyzed by intention to treat.

Comparing atorvastatin vs. placebo, the mean LDL was 73 vs. 129. Before the study ended, 15.4% vs. 20.2% of patients discontinued the atorvastatin.

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The rates of stroke (fatal or nonfatal) were 11.2% vs. 13.1% (P =.05, NNT 53), of which 10.4% vs. 11.8% were nonfatal (P =.14) and 1% vs. 1.7% were fatal (P =.04, NNT 143). Other outcomes that favored atorvastatin were rates of TIA (6.5% vs. 8.8%, P =.004, NNT 44), nonfatal MI (1.8% vs. 3.5%, P =.001, NNT 59), and major cardiovascular event (14.1% vs. 17.2%, P =.005, NNT 33). There were no significant differences in mortality (9.1% vs. 8.9%).

The only significant adverse effect was an elevation in alanine or aspartate aminotransferase more than three times the upper limit of normal, which occurred in 2.2% of atorvastatin patients compared with 0.5% of placebo patients (P <.001, NNH 58). Study treatment was discontinued due to adverse effects in 17.5% of atorvastatin patients compared with 14.5% of placebo patients (NNH 33).