Smoking diminishes the beneficial effect of statins: observations from the landmark trials.

The landmark statin trials showed a significant reduction in morbidity and mortality associated with ischemic heart disease. However, it may not be widely appreciated that smoking had a marked adverse effect on outcome in these trials. In both the primary and secondary prevention setting, the effect of smoking was broadly similar. Smoking markedly increased the risk of events in the placebo and treatment groups. For example, in the primary prevention trials, this risk was 74-86% higher when smokers were compared with nonsmokers in the placebo groups. The corresponding figures for the secondary prevention trials were 23-61%. The risk of events in untreated nonsmokers was of a similar order to that seen in smokers taking statins. Although statin treatment was associated with a significant reduction in events in smokers, the best outcome was observed in nonsmokers treated with statins (primary prevention: lovastatin or pravastatin; secondary prevention: pravastatin or simvastatin). The highest risk of events in any group was in the smokers on placebo. This information may increase clinician and patient awareness as to the marked harmful effect of smoking relative to effective, evidence-based treatment (ie, the use of statins).