Cholesterol reduction and non-illness mortality: Meta-analysis of randomised clinical trials

Abstract

Objective: To investigate the association between cholesterol lowering interventions and risk of death from suicide, accident, or trauma (non-illness mortality). Design: Meta-analysis of the non-illness mortality outcomes of large, randomised clinical trials of cholesterol lowering treatments. Studies reviewed: 19 out of 21 eligible trials that had data available on non-illness mortality. Interventions reviewed: Dietary modification, drug treatment, or partial ileal bypass surgery for 1-10 years. Main outcome measure: Deaths from suicides, accidents, and violence in treatment groups compared with control groups. Results: Across all trials, the odds ratio of non-illness mortality in the treated groups, relative to control groups, was 1.18 (95% confidence interval 0.91 to 1.52; P = 0.20). The odds ratios were 1.28 (0.94 to 1.74; P = 0.12) for primary prevention trials and 1.00 (0.65 to 1.55; P = 0.98) for secondary prevention trials. Randomised clinical trials using statins did not show a treatment related rise in non-illness mortality (0.84, 0.50 to 1.41; P = 0.50), whereas a trend toward increased deaths from suicide and violence was observed in trials of dietary interventions and non-statin drugs (1.32, 0.98 to 1.77; P = 0.06). No relation was found between the magnitude of cholesterol reduction and non-illness mortality (P = 0.23). Conclusion: Currently available evidence does not indicate that non-illness mortality is increased significantly by cholesterol lowering treatments. A modest increase may occur with dietary interventions and non-statin drugs.