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CLINICAL RESEARCH: LIPID-LOWERING AND STROKE

Cholesterol-Lowering Interventions and Stroke

Insights From a Meta-Analysis of Randomized Controlled Trials

Raffaele De Caterina, MD, PhD^_*,,_*, Marco Scarano, MSc, RosaMaria Marfisi, MSc, Giuseppe Lucisano, MSc, Francesco Palma, MD^_*, Alfonso Tatasciore, MD^_* and Roberto Marchioli, MD

^_* Institute of Cardiology and University Cardiology Division, "G. d'Annunzio" University, Chieti, Italy
National Research Council (CNR) Institute of Clinical Physiology and Fondazione G. Monasterio, Pisa, Italy
Consorzio Mario Negri Sud, S. Maria Imbaro, Chieti, Italy

Manuscript received April 27, 2009; revised manuscript received July 20, 2009, accepted July 27, 2009.

^_* Reprint requests and correspondence to: Dr. Raffaele De Caterina, Institute of Cardiology, "G. d'Annunzio" University, Chieti, c/o Ospedale SS Annunziata, Via dei Vestini, Chieti 66013, Italy (Email: rdecater{at}unich.it).

Objectives: This meta-analysis was performed to determine the effects of various cholesterol-lowering treatments on the risk of stroke and its relationship with the extent of cholesterol lowering.

Background: Statins reduce the incidence of stroke, and it has been proposed that such effect is independent of cholesterol lowering and is explained by alternative mechanisms.

Methods: We performed a meta-analysis of randomized trials of cholesterol-lowering treatments in cardiovascular disease reporting on stroke, involving 266,973 patients investigated and a cumulative 946,582 person-years of exposure, and a meta-regression analysis of the extent of stroke reduction as a function of changes in total cholesterol.

Results: The odds ratio (OR) for the incidence of stroke in actively treated groups versus controls was 0.88 (95% confidence interval: 0.83 to 0.94, p < 0.001). No treatment affected fatal strokes. Whereas statins decreased the risk of total stroke significantly (OR: 0.85, 95% confidence interval: 0.78 to 0.92; p < 0.001), the benefit of nonstatin interventions was smaller and not statistically significant (diet OR: 0.92, fibrates OR: 0.98, other treatments OR: 0.81). We found a significant relationship between percent reduction of total (and low-density lipoprotein) cholesterol and percent reduction of total strokes (p = 0.0017), with each 1% reduction of total cholesterol predicting a 0.8% relative risk reduction of stroke. We found no significant association between stroke reduction and changes of high-density lipoprotein cholesterol levels, and inconsistent associations with reduction of triglycerides.

Conclusions: Among cholesterol-lowering treatments, statins are the most effective at decreasing the risk of total stroke, but their benefit is proportional to the percent reduction of total cholesterol and low-density lipoprotein cholesterol. No lipid-lowering intervention was associated with a reduction of fatal stroke.

Key Words: statins • HMG-CoA reductase inhibition • stroke • cholesterol • pleiotropic effects • neuroprotection

Abbreviations and Acronyms   CHD = coronary heart disease   CI = confidence interval   HDL-C = high-density lipoprotein cholesterol   LDL-C = low-density lipoprotein cholesterol   OR = odds ratio   RCT = randomized clinical trial   RR = relative risk   TC = total cholesterol

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