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1 Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Collet J-P, Cuisset T, Rangé G, et al. Bedside monitoring to adjust antiplatelet therapy for coronary stenting. N Engl J Med 2012;367: DOI: /NEJMoa

2 Supplementary Appendix Figures Author s affiliations Contributors Conflict of Interest Acknowledgments Study Investigators 1

3 Appendix Figure legends Figure S1: Study flow chart Figure S2: Flow diagram of antiplatelet therapy during the entire study in both groups. Figure S3: Rate of patients (in the monitoring group) with high on-treatment platelet reactivity before first treatment adjustment and stenting and, days after stenting but before second treatment adjustment. Average levels of platelet reactivity are presented below the figure. Figure S4: Primary end point (top - A) and main secondary end point (Bottom B) in pre-specified subgroups Figure S5: Rate of the primary end point when using 5 times the upper limit of normal of troponin in the definition of type 4a myocardial infarction (sensitivity analysis). Figure S6: Rate of the primary end point when using 10 times the upper limit of normal of troponin in the definition of type 4a myocardial infarction (sensitivity analysis). 2

4 Figure S randomizations by IVRS 1252 were assigned to conventional therapy 8 randomization technical errors/ 2 ineligible patients 15 absence of adequately signed consent 1248 were assigned to monitoring therapy 4 randomization technical errors/ 6 ineligible patients 25 absence of adequately signed consent 1227 in conventional therapy arm 1213 in monitoring therapy arm 11 withdrew consent/1 investigator s decision 32/27/47 were lost to follow up at D14/M6/M12 respectively 19 withdrew consent/2 investigator s decision 8/40/23 were lost to follow up at D14/M6/M12 respectively 1227 were included in the intention-to-treat analysis 1213 were included in the intention-to-treat analysis 3

5 Figure S2 4

Figure S3 40 35 34,5 Baseline Day -14-30 30 25 20 15 P<0.001 15,6 P<0.

on-aspirin platelet reactivity Baseline 14 days P value PRU level, mean

6 Figure S ,5 Baseline Day P< ,6 P< ,6 5 3,9 0 High on-clopidogrel platelet reactivity High on-aspirin platelet reactivity Baseline 14 days P value PRU level, mean 180 (96;257) 141 (78;202.5) <.0001 ARU level, mean 411 (388; 480) 398 (386; 446) <

7 Figure S4 A M o nito ring T reatment C o nventio nal treatment n % n % R elative risk (95%C I) P Interactio n Full population % ,1% 1.13 (0.98 ; 1.29) 0.1 Age > % % 1.28 (0.90; 1.82) Age % % 1.10 (0.95; 1.28) 0.43 Women % % 1.03 (0.76; 1.40) Men % % 1.15 (0.99; 1.35) 0.52 BMI % % 1.20 (1.03; 1.41) BMI > % % 0.85 (0.63; 1.16) 0.05 No diabetes % % 1.12 (0.94; 1.33) Diabetes % ,10% 1.14 (0.90; 1.43) 0.91 No Smoking % % 1.18 (1.01; 1.38) Smoking % % 0.97 (0.73; 1.29) 0.25 No ACS % % 1.10 (0.93; 1.29) ACS % % 1.20 (0.92; 1.56) 0.57 Number of stent= % % 1.17 (0.96; 1.42) Number stent % ,20% 1.06 (0.87; 1.30) B M o nito ring T reatment C o nventio nal treatment R elative risk (95%C I) P Interactio n n % n % Full population % ,6% 1.06 (0.74; 1.52) 0.77 Age > % % 0.89 (0.36; 2.19) Age % % 1.09 (0.73; 1.62) 0.69 Women % % 0.96 (0.48; 1.91) M en % % 1.11 (0.72; 1.70) 0.72 BMI % % 1.12 (0.73; 1.71) BMI > % % 0.91 (0.43; 1.90) 0.63 No diabetes % % 1.00 (0.63; 1.60) Diabetes % % 1.14 (0.64; 2.02) 0.74 No Smoking % % 1.11 (0.74; 1.66) Smoking % % 0.87 (0.37; 2.04) 0.61 No ACS % % 0.98 (0.63; 1.53) ACS % % 1.23 (0.65; 2.33) 0.57 Number of stent= % % 1.30 (0.79; 2.15) Number stent % % 0.81 (0.46; 1.43) Favours monitoring Favours conventional 6

8 Event probability Primary end point (10 times ULN) Event Probability Primary end point (5 times ULN) Figure S5 Conventional Monitoring HR = 1.17 [ ] p= Follow-up (Days) N at risks Conventional Monitoring Figure S6 Conventional Monitoring HR = 1.23 [ ] p= Follow-up (Days) N at risks Conventional Monitoring

9 Author s affiliations JPC, GM, JS, SOC, JA, MK, PS, OB, FB, Institut de Cardiologie Hôpital Pitié-Salpêtrière (APHP) and Université Pierre et Marie Curie, Paris, France GC, Cardiologie, CHU Carémeau, Nîmes, France TC, Département de Cardiologie, CHU La Timone, Marseille, France SE, Cardiologie, CH de Lagny - Marne la Vallée, Lagny-sur-Marne, France GR, Les Hôpitaux de Chartres, Le Coudray, France PH, Cardiologie, Hôpital Lariboisière (AP-HP), Paris, France HR, EV, Unité de Recherche Clinique-Hôpital Lariboisière (APHP), Paris, France and Université Denis Diderot, Paris, France PA, Centre Hospitalier Bichat (APHP), Paris, France JM, HIA Du Val de Grâce, Paris, France. EVB, CHRU, Lille, France DC, CHU Rangueil, Toulouse, France CP, Clinique Ste Clotilde, La Réunion PM, CHU de Clermont-Ferrand, France ZB, Centre Hospitalier de Bastia, France LB, Centre Hospitalier Annecy, France CSE, CHU Trousseau, Tours, France. Contributors GM, JPC and EV designed the study, analyzed and interpreted the data. GC, TC, SE, GR, JPC, GM participated to the Steering Committee, contributed to implementation of the study, enrolment and follow-up of patients, and revised the manuscript. HR and EV did all statistical analyses. GM and JPC wrote the first draft and submitted the final version for publication. TC, GR, GC, SE, CP, PH, PM, DC, ZB, LB, EV, PA, JM, PS, SOC, JA, MK, CSE, OB, FB, JS participated to the study, commented on the manuscript and approved the final version. All authors have seen the version of the article and agree with the content and conclusions. Conflict of Interest J-PC reports receiving research grants from Bristol-Myers Squibb, Sanofi-Aventis, Eli Lilly, Medtronic, Boston Scientific, Cordis, Stago, Fondation de France, INSERM, Nanospheres, Fédération Française de Cardiologie and SociétéFrançaise de Cardiologie; consulting fees from Sanofi-Aventis, Eli Lilly, and Bristol- Myers Squibb; and lecture fees from Bristol-Myers Squibb, Sanofi-Aventis, Eli Lilly, and AstraZeneca. TC reports receiving a research grant from Eli Lilly; consulting fees from Daiichi Sankyo and Eli Lilly; support for travel to meetings from Eli Lilly Daiichi Sankyo; lecture fees from AstraZeneca, Eli Lilly, Sanofi, Abbott Vascular, Biotronik, Boston Scientific, Cordis, Edwards, Iroko Cardio, Medtronic, Servier; travel and meetings expenses from Abbott Vascular, AstraZeneca, Biotronik, Boston Scientific, Cordis, Daiichi Sankyo, Edwards, Eli Lilly, Iroko Cardio, Medtronic, Servier. GR has no COIs. GC reports receiving a research grant from la Fédération Française de Cardiologie; consultant fees from Abbott Vascular, AstraZeneca, CLS, Behring, Daiichi Sankyo, and Eli Lilly; and lecture fees from Abbott Vascular, AstraZeneca, Biotronik, CLS Behring, Daiichi Sankyo, Eli Lilly, and Iroko Cardio. SE has no COIs. CP reports receiving research support and consulting fees from Sanofi-Aventis and The Medicines Company. PH has no COIs. PM: Consultancy: St Jude Medical, Terumo. ZB has no COIs. DC has no COIs. LB has no COIs. 8

10 EVB has no COIs. HR has no COIs. PA has no COIs. JM has no COIs. PS reports receiving fees for board membership from BMS; consulting fees from Daiichi Sankyo and Eli Lilly; lecture fees from MSD and Sanofi. SOC reports receiving grants from A. Menarini and the European Society of Cardiology. JA reports receiving a grant from FERCM. MK reports receiving a grant from Fédération Française de Cardiologie. CSE has no COIs. OB has no COIs. FB reports receiving grants from Pfizer, Brahms and Fédération Française de Cardiologie; lecture fees from Roche, Sanofi-Aventis, Pfizer and Astellas. JS reports receiving research grants from Sanofi-Aventis, Daiichi-Sankyo, Eli Lilly, Brahms, INSERM, FédérationFrançaise de Cardiologie, and SociétéFrançaise de Cardiologie; consulting fees from Daiichi- Sankyo and Eli Lilly; and speakers honoraria from AstraZeneca, Daiichi Sankyo, Eli Lilly, and Servier. EV reports receiving research grants from Sanofi-Aventis, Medtronic, Cordis, Boston Scientific, Fondation SGAM, Fondation de France, ACTION and APHP; consulting fees from Pfizer, Eli Lilly, Sanofi, LFB, Abbott, Frensenius; grant from Boehringer Ingelheim; lecture fees from Merck, Pfizer. GM reports receiving grant support from Abbott Vascular, Boston Scientific, Cordis, Eli Lilly, Fédération Française de Cardiologie, Fondation de France, Guerbet Medical, INSERM, ITC Edison, Medtronic, Pfizer, Sanofi-Aventis, Société Française de Cardiologie, and Stago; consulting or board fees and lecture fees from AstraZeneca, Bayer, Boehringer Ingelheim, Cardiovascular Research Foundation, Cleveland Clinic Research Foundation, Daiichi-Sankyo, Duke Institute, Eli Lilly, Europa, Lead-up, GlaxoSmithKline, Institut de Cardiologie de Montréal, Menarini, Nanospheres, Novartis, Pfizer, Portola, Sanofi -Aventis, The Medicines Company, and the TIMI study group. Acknowledgments: Yannick Vacher, Abdel Ait Bachir, Andrea Bardon, Nabil Brouk, Julie Bussone, Hermione Folal, Vanessa Gallois, Sophie Gérard,Véronique Jouis, Azizath Karibou, Nathalie Kingue,Valérie Mazur, Hélène Mauro, Ghislain N Gouala, Luminita Neculaita, Sissel Paulsrud, Virginie Rochaud, Corinne Tchokothe. Study investigators Centers: CHU Pitié-Salpêtrière, Paris, Prs Montalescot/Collet Hôpital Cardiologique du Haut Lévêque, Pessac, Pr Coste Hôpital Pontchaillou, Rennes, Pr Le Breton CH de Lagny, Marne-la-Vallée, Drs Elhadad/Cohen Hôpital privé Beauregard, Marseille, Dr Wittenberg Hôpital Arnaud de Villeneuve, Montpellier, Pr Leclercq Hôpital Cochin, Paris, Dr Varenne CHU Carémeau, Nîmes, Drs Ledermann/Cayla Hôpital de la Timone, Marseille, Drs Cuisset Hôpital Cardiologique Albert Calmette, Lille, Dr Van Belle Hôpital Lariboisière, Paris, Pr Henry CHU Jean Minjoz, Besançon, Pr Bassand Hôpital Cardio-Vasculaire Louis Pradel, Lyon, Pr Finet Hôpital Nord Marseille Dr Paganelli 9

11 Hôpital de Rangueil, Toulouse, Dr Carrié Clinique de l'orangerie, Strasbourg, Dr Aleil CH de la Région Annecienne, Annecy, Dr Belle Clinique Nantaise, Nantes, Dr Brunel CH de Chartres, Dr Rangé CH d Avignon, Drs Pansieri/Barney GH du Centre Alsace, Drs Lhoest/Levai CH Marie Lannelongue, Le Plessis-Robinson, Dr Caussin CH de Cannes, Drs Tibi/Zemour Hôpital François Mitterrand, Pau, Dr Delarche Hôpital Saint-Joseph, Marseille, Dr D Houdain CHU de Poitiers, Dr Christiaens Clinique Sainte Clothilde, La Réunion, Dr Pouillot Polyclinique de Bordeaux Caudéran, Bordeaux, Dr Casteigt Hôpital Pasteur, Nice, Pr Ferrari CH Dijon, Pr Cottin CHR Strasbourg, Pr Ohlmann CH Lens, Dr Pecheux CH de Compiègne, Dr Sayah CH Clermont-Ferrand, Dr Motreff Clinique du Tonkin, Villeurbanne, Dr Champagnac Clinique de l Europe, Amiens, Dr Py Clinique du Parc, Castelnau-le-Lez, Dr Shadfar CH de Bastia, Dr Boueri 10

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