BACKGROUND: Patients enrolled in randomized clinical trials (RCTs) may not reflect those seen in real-life practice. Our goal was to compare patients eligible for enrollment but not enrolled in contemporary RCTs of reperfusion therapy with patients who would have been ineligible and also with patients with acute myocardial infarction (AMI) participating in RCTs. METHODS: Consecutive patients with AMI (n = 8469) enrolled in the GRACE registry (Global Registry of Acute Coronary Events) were divided into 3 groups: RCT participants (11%; n = 953), eligible nonenrolled patients (55%; n = 4669), and ineligible patients (34%; n = 2847). Our main outcome measures were hospital mortality rates. RESULTS: Based on baseline characteristics or GRACE risk-score distribution, RCT participants had the lowest a priori risk of death; eligible patients had a higher risk; and ineligible patients had the highest risk. Actual hospital mortality showed a similar gradient (3.6%, 7.1%, and 11.4%, respectively) (P<.001). Multivariable analysis adjusting for baseline risk, use and type of reperfusion therapy, and delay from symptom onset to admission consistently showed a higher mortality rate for eligible nonenrolled patients than for RCT participants (odds ratio, 1.61; 95% confidence interval, 1.06-2.43; and odds ratio, 1.97; 95% confidence interval, 1.24-3.13, respectively). CONCLUSIONS: Patients with AMI participating in RCTs have a lower baseline risk and experience lower mortality than nonenrolled patients, even when they are trial eligible. This difference is not entirely explained by differences in baseline risk, use and type of reperfusion therapy, and/or delays in presentation. Caution is necessary when extending the findings obtained in RCTs to the general population with AMI.

PURPOSE: To determine the impact of cigarette smoking on the presentation, treatment, and in-hospital outcomes of patients admitted with the full spectrum of acute coronary syndromes. METHODS: GRACE is a multinational observational registry involving 94 hospitals in 14 countries. This analysis is based on 19,325 patients aged at least 18 years admitted for acute coronary syndromes as a presumptive diagnosis with at least one of the following: electrocardiographic changes consistent with acute coronary syndromes, serial increases in serum biochemical markers of cardiac necrosis, and/or documentation of coronary artery disease. The main outcomes measured were mode of presentation, treatment and in-hospital death in the ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, and unstable angina groups to assess the impact of smoking status. RESULTS: Smokers were more frequently diagnosed with ST-segment elevation myocardial infarction (46.0%) than former smokers (27.4%) and non-smokers (30.2%) (P<0.001). Smokers were mostly men, were younger and more aggressively treated than former smokers and non-smokers across the three acute coronary syndrome groups. Unadjusted in-hospital mortality rates were lower in smokers compared with former smokers and non-smokers in the study population (3.3%, 4.5%, and 6.9%, respectively, P<0.001), and in the ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction groups. However, by multivariate logistic analysis, the adjusted in-hospital mortality rate was similar regardless of smoking status. CONCLUSIONS: There is no survival advantage related to current or prior cigarette smoking in patients admitted with acute coronary syndromes, regardless of presentation. In this large multinational registry, the smokers' paradox does not exist.