Differential effects of lipid-lowering therapies on stroke prevention: A meta-analysis of randomised trials

Background: Previous overviews have suggested that the FIMG-CoA reductase inhibitors (statins), but not other lipid lowering therapies (LLTs), may reduce stroke incidence in coronary patients. Our objective was to investigate the amplitude and sources of heterogeneity of LLT effects on stroke prevention. Methods: A literature search was performed from 1966-2001 to identify all English-language published trials testing LLT. We then conducted a meta-analysis including randomised primary and secondary coronary heart disease prevention trials, which tested statins, nonstatins, diet or other interventions, and providing data on stroke incidence. Results: The overall meta-analysis (38 individual trials, 83 161 patients, mean follow-up of 4.7 years) showed a significant relative risk reduction (RRR) of strokes by LLTs of 17% (p < 0.001), without significant heterogeneity between trials and between subgroups according to either the type of prevention (primary or secondary prevention) or type of LLT. Most demonstrative effects was obtained however with statins (RRR = 26%). Effect model analysis showed that the treatment benefits appeared constant whatever the risk of stroke, suggesting that LLTs may be effective in a population with a higher risk of stroke. Weighted regression showed a significant correlation between the RRR of stroke and total cholesterol levels (baseline, final, and change). Only final cholesterol level allowed a clear separation between benefit (RRR > 0) and no effect (RRR < 0) of LLTs on stroke incidence, with a cut-off for benefit of 6.0 mmol/L. Conclusion: LLTs reduce stroke incidence in coronary patients, especially when total cholesterol is under 6.0 mmol/L, this explains the better results obtained with statins.