The "smoker's paradox" in patients with acute coronary syndrome: a systematic review

Abstract

Background: Smokers have been shown to have lower mortality after acute coronary syndrome than non-smokers. This has been attributed to the younger age, lower co-morbidity, more aggressive treatment and lower risk profile of the smoker. Some studies, however, have used multivariate analyses to show a residual survival benefit for smokers; that is, the "smoker's paradox". The aim of this study was, therefore, to perform a systematic review of the literature and evidence surrounding the existence of the "smoker's paradox".

Methods: Relevant studies published by September 2010 were identified through literature searches using EMBASE (from 1980), MEDLINE (from 1963) and the Cochrane Central Register of Controlled Trials, with a combination of text words and subject headings used. English-language original articles were included if they presented data on hospitalised patients with defined acute coronary syndrome, reported at least in-hospital mortality, had a clear definition of smoking status (including ex-smokers), presented crude and adjusted mortality data with effect estimates, and had a study sample of > 100 smokers and > 100 non-smokers. Two investigators independently reviewed all titles and abstracts in order to identify potentially relevant articles, with any discrepancies resolved by repeated review and discussion.

Results: A total of 978 citations were identified, with 18 citations from 17 studies included thereafter. Six studies (one observational study, three registries and two randomised controlled trials on thrombolytic treatment) observed a "smoker's paradox". Between the 1980s and 1990s these studies enrolled patients with acute myocardial infarction (AMI) according to criteria similar to the World Health Organisation criteria from 1979. Among the remaining 11 studies not supporting the existence of the paradox, five studies represented patients undergoing contemporary management.

Conclusion: The "smoker's paradox" was observed in some studies of AMI patients in the pre-thrombolytic and thrombolytic era, whereas no studies of a contemporary population with acute coronary syndrome have found evidence for such a paradox.

Figure 1

Selection of studies.

Figure 2

Forest plots of adjusted mortality in smokers vs. non-smokers. Odds ratios (OR)/hazard ratios (HR) with 95% confidence intervals for death during follow-up for smokers compared with non-smokers in the studies included. Circles indicate data derived from randomised trials. Squares indicate data derived from observational studies or registries. Open symbols indicate contemporary studies enrolling patients mainly after 2000. Closed symbols indicate older studies enrolling patients in the pre-thrombolytic and thrombolytic era. Symbol size reflects the sample size of the studies and registries. *Inverted OR from original paper. ^§The adjusted HR is for the conservative treatment cohort (2003) only. For the invasive cohort (2006) there was no difference in mortality for smokers and non-smokers (data not published).