Person:

Bhatt, Deepak

Background: The relationship between “on‐treatment” low platelet reactivity and longitudinal risks of major bleeding dual antiplatelet therapy following acute coronary syndromes remains uncertain, especially for patients who do not undergo percutaneous coronary intervention. Methods and Results: We analyzed 2428 medically managed acute coronary syndromes patients from the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trial who had serial platelet reactivity measurements (P2Y12 reaction units; PRUs) and were randomized to aspirin+prasugrel versus aspirin+clopidogrel for up to 30 months. Contal's method was used to determine whether a cut point for steady‐state PRU values could distinguish high versus low bleeding risk using 2‐level composites: Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) severe/life‐threatening or moderate bleeding unrelated to coronary artery bypass grafting (CABG) and non‐CABG Thrombolysis In Myocardial Infarction (TIMI) major or minor bleeding. Exploratory analyses used 3‐level composites that incorporated mild and minimal GUSTO and TIMI events. Continuous measures of PRUs (per 10‐unit decrease) were not independently associated with the 2‐level GUSTO (adjusted hazard ratio [HR], 1.01; 95% CI, 0.96–1.06) or TIMI composites (1.02; 0.98–1.07). Furthermore, no PRU cut point could significantly distinguish bleeding risk using the 2‐level composites. However, the PRU cut point of 75 differentiated bleeding risk with the 3‐level composites of GUSTO (26.5% vs 12.6%; adjusted HR, 2.28; 95% CI, 1.77–2.94; P<0.001) and TIMI bleeding events (25.9% vs 12.2%; adjusted HR, 2.30; 95% CI, 1.78–2.97; P<0.001). Conclusions: Among medically managed non‐ST‐segment elevation acute coronary syndromes patients receiving prolonged dual antiplatelet therapy, PRU values were not significantly associated with the long‐term risk of major bleeding events, suggesting that low on‐treatment platelet reactivity does not independently predict serious bleeding risk. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00699998.

Background: Prior studies have found that smokers undergoing thrombolytic therapy for ST‐segment elevation myocardial infarction have lower in‐hospital mortality than nonsmokers, a phenomenon called the “smoker's paradox.” Evidence, however, has been conflicting regarding whether this paradoxical association persists in the era of primary percutaneous coronary intervention. Methods and Results: We used the 2003–2012 National Inpatient Sample databases to identify all patients aged ≥18 years who underwent primary percutaneous coronary intervention for ST‐segment elevation myocardial infarction. Multivariable logistic regression was used to compare in‐hospital mortality between smokers (current and former) and nonsmokers. Of the 985 174 patients with ST‐segment elevation myocardial infarction undergoing primary percutaneous coronary intervention, 438 954 (44.6%) were smokers. Smokers were younger, were more often men, and were less likely to have traditional vascular risk factors than nonsmokers. Smokers had lower observed in‐hospital mortality compared with nonsmokers (2.0% versus 5.9%; unadjusted odds ratio 0.32, 95% CI 0.31–0.33, P<0.001). Although the association between smoking and lower in‐hospital mortality was partly attenuated after baseline risk adjustment, a significant residual association remained (adjusted odds ratio 0.60, 95% CI 0.58–0.62, P<0.001). This association largely persisted in age‐stratified analyses. Smoking status was also associated with shorter average length of stay (3.5 versus 4.5 days, P<0.001) and lower incidence of postprocedure hemorrhage (4.2% versus 6.1%; adjusted odds ratio 0.81, 95% CI 0.80–0.83, P<0.001) and in‐hospital cardiac arrest (1.3% versus 2.1%; adjusted OR 0.78, 95% CI 0.76–0.81, P<0.001). Conclusions: In this nationwide cohort of patients undergoing primary percutaneous coronary intervention for ST‐segment elevation myocardial infarction, we observed significantly lower risk‐adjusted in‐hospital mortality in smokers, suggesting that the smoker's paradox also applies to ST‐segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention.