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Cigarette smokers have an unexplained low mortality following ST-segment elevation acute myocardial infarction (STEMI). Our aim was to determine whether the presence of active smoking has a beneficial effect on myocardial reperfusion following primary percutaneous intervention (PCI).A total of 140 STEMI patients treated with primary PCI were included in the analysis. All patients have 24-h ST-segment monitoring, each analyzed by an independent, blinded core laboratory. We divided the population according to the smoking status: active (n = 56) and nonactive smokers (n = 84).Both groups had similar baseline characteristics, except that active smokers were younger than nonsmokers. Postprocedural thrombolysis in myocardial infarction (TIMI) flow grade and TIMI frame were better in smokers whereas myocardial blush grade was similar between groups. Percentage of complete (≥70%) ST-segment resolution (STR) at 60 min was higher in active smokers than in nonactive smokers (76.4 versus 50%, P = 0.002). Multivariate logistic regression analysis identified active smoking as an independent predictor of complete STR at 60 min (OR 3.47; 95% CI 1.48–8.14; P = 0.004). At 30 days, no significant differences were found either in mortality (P = 0.62) or in major adverse cardiac events rates (death, reinfarction and congestive heart failure; P = 0.82) between the two groups.In STEMI patients undergoing primary PCI, active smoking is associated with better myocardial reperfusion than nonsmoking. This finding may be the mechanism behind the smoker's paradox and its beneficial effect in the short-term clinical outcome. These results await further confirmation in larger primary PCI databases.