1. Effects of Clinical Characteristics and Treatments on Gender Difference in Outcomes after Acute Myocardial Infarction. A propensity score-matched analysis François Schiele, MD, PhD, Nicolas Meneveau, MD, PhD, Marie France Seronde, MD, Vincent Descotes-Genon, MD, Joanna Dutheil, MD, Romain Chopard, MD, Fiona Ecarnot, and Jean-Pierre Bassand, MD. On behalf on the “Reseau de Cardiologie de Franche Comté” Department of Cardiology, University Hospital Jean Minjoz, Besançon, France. Confli c t of Interest to Declare : Research Contracts and Consulting Servier, Sanofi, GSK, Astra-Zeneca, Takeda, Lilly

8. Baseline characteristics (1) Variables Women (%) Men (%) P Value Chi2/ t N 1119 (32) 2391 (68) STEMI 461 (41) 1117 (47) 0.0008 9.38 NSTEMI 658 (59) 1274 (53) <0.0001 9.38 Age (SD) 74 (13) 64 (13) <0.0001 18.9 Diabetes 301 (27) 495 (21) <0.0001 16.7 Hypertension 762 (68) 1143 (48) <0.0001 12.7 Hypercholesterolemia 451 (40) 1132 (47) <0.0001 15.9 Smoker 258 (23) 1583 (66) <0.0001 56.7 Previous MI 151 (13) 449 (19) <0.0001 15.2 Previous angioplasty 94 (8) 349 (15) <0.0001 26.5 Previous coronary surgery 37 (3) 105 (4) 0.12 2.33 Previous Stroke 79 (7) 121 (5) 0.002 5.6 Per. Vessel Disease 86 (8) 286 (12) <0.0001 14.8

9. Baseline characteristics (2) Variables Women (%) Men (%) P Value Chi2/ t N 1119 (32) 2391 (68) Time to admission STEMI 4 [2;15] 3 [2 ;9] <0.0001 Admission heart rate 80 (20) 77 (20) <0.0001 4.0 Admission Systolic BP 134 (29) 130 (28) 0.79 0.09 Killip class >2 94 (8) 127 (5) <0.0001 12.3 Cardiogenic shock 48 (4) 94 (4) 0.61 0.25 GRACE risk score 147 [124 ;167] 132 [110 ;152] <0.0001 Admission Glucose 7 (4.4) 6.7 (3.5) 0.0035 2.99 BNP 480 [180;1202] 217 [83;544] <0.0001 Hs-CRP 8 [3;27] 6 [2;22] <0.0001

10. In-hospital Treatments Variables Women (%) Men (%) P Value Chi2/ t Angiography 805 (72) 2080 (87) <0.0001 130 No obstructive disease 112(14) 92(4) <0.001 83 PCI of infarct related artery 552(49) 1662(69) <0.0001 133 GPIIbIIIa inhibitors (NSTEMI) 271 (40) 682 (53) <0.0001 25.9 Reperfusion (STEMI) 281/461 (61) 843/1117 (75) <0.001 30.5 Primary PCI (STEMI) 215/461 (47) 615/1117 (55) <0.0001 19.0 Thrombolysis (STEMI) 66/461 ( 14) 228/1117 (20) <0.009 8.0 Aspirin 1089 (97) 2360 (99) <0.0001 16.8 Clopidogrel 1075 (96) 2290 (96) <0.0001 25.0 Aspirin + Clopidogrel 1035 (92) 2290 (96) <0.0001 31.8 ACEI / ARB 667 (60) 2052 (86) <0.0001 23.9 Betablockers 791 (71) 1847 (77) <0.0001 17.5 Statins 982 (88) 2296 (96) <0.0001 75.3

11. Selection of the matched populations 3510 patients with Acute Myocardial Infarction 1578 (45%) STEMI, 1932 (55%) NSTEMI 1119 (32%) Women, 2391 (68%) Men Matching on propensity score 1 = 649 pairs Comparison of treatments Comparison of mortality Comparison of mortality Propensity score 1 (being male) with baseline characteristics Propensity score 2 (being male) with baseline characteristics and treatments Matching on propensity score 2 = 584 pairs

12. Effect of matching on sex differences P values for the difference between men and women Unmatched dataset 0.05

13. Effect of matching on sex differences P values for the difference between men and women Unmatched dataset Matched #1 dataset 0.05

14. Effect of matching on sex differences P values for the difference between men and women Unmatched dataset Matched #1 dataset Matched #2 dataset 0.05

15. KM Cumulative mortality Unmatched n=3510 p=0.001 Unmatched n=3510 p=0.001 Matched #1 n=649 pairs p=0.23 Log-Rank test: p=0.95 Days 0 5 10 20 30 At risk 584 574 565 544 529 584 573 562 550 530 Women Men Unmatched n=3510 p=0.001 Matched #1 n=649 pairs p=0.23 Matched #2 n=584 pairs p=0.95

16. 0.5 0.8 1 1.5 2 4 Aspirin unmatched OR= 1.35 [1.06; 1.80] Matched #1 OR= 1.10 [0.46; 2.62] Clopidogrel unmatched OR= 1.65 [1.38; 2.01] Matched #1 OR= 1.04 [0.58; 1.84] Aspirin and Clopidogel unmatched OR= 1.67 [1.40; 2.01] Matched #1 OR= 1.10 [0.46; 1.63] ACEI or ARB unmatched OR= 1.42 [1.24; 1.65] Matched #1 OR= 1.29 [0.97; 1.70] Beta blocker unmatched OR= 1.31 [1.15; 1.49] Matched #1 OR= 1.02 [0.64; 1.29] GPIIbIIIa (NSTEMI) unmatched OR= 1.66 [1.43; 1.96] Matched #1 OR= 1.40 [0.94; 1.56] Coronary Angiography unmatched OR= 2.82 [2.40; 3.41] Matched #1 OR= 1.57 [1.10; 2.18] Reperfusion /PPCI unmatched OR= 1.56 [1.29; 1.89] Matched #1 OR= 1.24 [1.12; 1.71] Reperfusion /FL unmatched OR= 1.82 [1.24; 2.12] Matched #1 OR= 1.72 [1.08; 2.73] In-Hospital mortality unmatched OR= 0.50 [0.37; 0.62] Matched #1 OR= 0.52 [0.32; 0.83] Matched #2 OR= 0.75 [0.45; 1.23] 30 day mortality unmatched OR= 0.53 [0.42; 0.57] Matched #1 OR= 0.70 [0.46; 1.01] Matched #2 OR= 0.89 [0.57; 1.36] Odds ratios for men versus women

17. Interaction between Gender and type of MI Mort ality more than twice as high in women than in men in STEMI, but no difference in NSTEMI patients; significant interaction No higher mortality and no interaction after adjustment for characteristics No higher mortality and no interaction after adjustment for characteristics and treatments Sub-groups (1) P=0.009 P=0.009 P=0.36 P=0.009 P=0.36 P=0.13

18. Interaction between Gender and Age: difference according to mean age Unadjusted cohort Sex-age interaction P=0.002 Matched #2 No sex-age interaction P=0.16 Matched #1 Sex-age interaction P=0.005 Sub-groups (2)