Letter to the Editor Does smoking habit affect the randomized comparison of 6 versus 24-month dual antiplatelet therapy duration? Insights from the PRODIGY trial Marianna Adamo a,b , Francesco Costa a,c , Pascal Vranckx d , Sergio Leonardi e , Eliano P. Navarese f,g , Hector M. Garcia-Garcia a,h , Marco Valgimigli a, ⁎ a Thoraxcenter, Erasmus Medical Center, Rotterdam, The Netherlands b Cardiothoracic Department, Spedali Civili, University of Brescia, Italy c Department of Clinical and Experimental Medicine, Policlinico “G. Martino”, University of Messina, Italy d Department of Cardiology and Critical Care Medicine, Hartcentrum Hasselt, Jessa Ziekenhuis, Hasselt, Belgium e Fondazione I.R.C.C.S. Policlinico San Matteo, Pavia, Italy f Department of Internal Medicine, Division of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University, Düsseldorf, Germany g Systematic Investigation and Research on Interventions and Outcomes (SIRIO) MEDICINE Research Network, Düsseldorf, Germany h Cardialysis, Rotterdam, The Netherlands article info Article history: Received 1 April 2015 Accepted 18 April 2015 Available online 22 April 2015 Keywords: Smoking Clopidogrel Outcome Pharmacodynamics studies reported a greater inhibition of platelet aggregation among clopidogrel treated patients in smokers compared with non-smokers [1]. Cigarette smoking increases the catalytic activity of CYP1A2, which mediates the first oxidative step in the conversion of pro-drug clopidogrel to its active metabolite [2]. Therefore, in clopidogrel treated patients smoking habit may increase the effect of treatment, potentially leading to a higher protection against ischaemic events, but also to a higher bleeding risk. Based on available evidence, the impact of smoking habit on outcomes remains unclear [3–8]. We investigated whether smoking status may influence the effect of dual antiplatelet therapy (DAPT) duration with respect to ischaemic and bleeding events in an all-comer PCI population who were randomized either 6-month (short-term) or 24-month (long-term) treatment with clopidogrel on top of aspirin after coronary stenting. The design of the Prolonging Dual Antiplatelet Treatment After Grading Stent Induced Intimal Hyperplasia Study (PRODIGY) was previ- ously reported [9,10]. The study was conducted according to the ethical guidelines of the Declaration of Helsinki. The Ethics Committee approved the protocol; the informed consent was achieved from each patient. Out of 2013 patients enrolled into the study, 33 died within 30 days and 10 withdrew consent. Smoking status was recorded in all but 8 pa- tients who were excluded from this analysis. The final population included 1962 patients: 984 were allocated to receive 24-month DAPT (222 smokers and 762 non-smokers) and 978 were assigned to 6-month DAPT (247 smokers and 731 non- smokers). Compared with non-smokers, smokers were younger, less frequent- ly had history of hypertension, myocardial infarction (MI) or coronary revascularization and more frequently presented with STEMI or had higher creatinine clearance. Demographic, clinical and procedural fea- tures were well balanced in the patients treated with long-term versus short-term DAPT within both smoker and non-smoker groups (Table 1). The primary efficacy end-point (all-cause death, MI or cerebrovas- cular accident – CVA – at 2 years) occurred in 165 (11.1%) non- smokers and in 32 (6.8%) smokers without significant differences between the two groups after adjustment for variables which were differently distributed at an alpha of 5% (HR 1.03 with CI 95% of 0.67–1.50; p = 0.989). Among patients allocated to the long-term DAPT arm compared with those assigned to receive the short-term DAPT, no significant differences of primary end-point rate were noted in both smokers (5.9% in the long-term vs 7.7% in the short-term DAPT arms; HR 0.70, 95% CI 0.34–1.45; p = 0.339) and non-smokers (11.3% in the long- term vs 10.8% in the short-term DAPT arms; HR 1.04, 95% CI 0.77– 1.41; p = 0.793) with no evidence of interaction between smoking habit and DAPT duration (P INT = 0.426) (Fig. 1). Similarly, no differ- ences between short and long-term DAPT groups in terms of both International Journal of Cardiology 190 (2015) 242–245 ⁎ Corresponding author at: Marco Valgimigli MD PhD FESC, Thoraxcenter, Ba 587, Erasmus MC, Rotterdam, The Netherlands. E-mail address: m.valgimigli@erasmusmc.nl (M. Valgimigli). http://dx.doi.org/10.1016/j.ijcard.2015.04.159 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved. Contents lists available at ScienceDirect International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard