Impact of cigarette smoking in high-risk patients participating in a clinical trial. A substudy from the Heart Outcomes Prevention Evaluation (HOPE) trial

Background In recent large cardiovascular trials done in stable patients, 14–31% of the participants were smokers; the consequences of smoking in these trials using medications known to reduce cardiovascular events, have not been assessed. Design We evaluated the cardiovascular outcomes according to smoking status of men and women participating in the Heart Outcomes Prevention Evaluation trial. Methods The occurrence of cardiovascular events was documented among participants who did not change their smoking status during the trial. There were 2728 ‘never smokers’, 5241 ‘former smokers’ and 936 ‘current smokers’, and all had stable cardiovascular disease or diabetes with at least one other risk factor. None had previous congestive heart failure or known left ventricular ejection fraction < 0.40. Results During the 4.5-year follow-up, there were 641 cardiovascular deaths, 978 myocardial infarctions, 358 strokes and 1021 deaths. In comparison to ‘never smokers’, smokers had relative risks adjusted for confounding variables including medications known to reduce cardiovascular mortality and morbidity, for cardiovascular death of 1.65 [95% confidence interval (CI), 1.28–2.14], for myocardial infarction of 1.26 (95% CI, 1.01–1.58), for stroke of 1.42 (95% CI, 1.00–2.04), and for total mortality of 1.99 (95% CI, 1.63–2.44). The rates of these events among ‘former smokers’ were not different from those of ‘never smokers’. Conclusions Smoking increased the risk of mortality and morbidity among high-risk patients despite the use of medications known to reduce cardiovascular events. Smoking cessation programs should be reinforced even for patients participating in clinical trials.