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A propensity score-matched analysis

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1 A propensity score-matched analysis
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. Conflict of Interest to Declare : Research Contracts and Consulting Servier, Sanofi, GSK, Astra-Zeneca, Takeda, Lilly

2 Women fare worse than men after acute MI
Women admitted for acute MI have % higher mortality at 30 days, as compared with men. This over-mortality is reduced after adjustment for age and co-morbidities. ISIS3 = il y a 20 ans (publié lancet 92) Malacrida, ISIS-3, N Engl J Med 1998;338:8-14

3 Women fare worse than men after acute MI
Women admitted for acute MI have % higher mortality at 30 days, as compared with men. This over-mortality is reduced after adjustment for age and co-morbidities. Sex-age interaction : discrepancy between studies Malacrida, N Engl J Med 1998;338:8-14 Greater difference with older age Vaccarino, N Engl J Med 1999;341:217-25 Decrease in difference with age Malacrida= 20 ans; Vaccarino = patients de NRMI, exclu les transferts, >90 ans, <30 ans, admission depuis 1998

4 Women fare worse than men after acute MI
Women admitted for acute MI have % higher mortality at 30 days, as compared with men. This over-mortality is reduced after adjustment for age and co-morbidities. Sex-age interaction : discrepancy between studies Sex-type of MI interaction : STEMI ≠ NSTEMI Meta analyse depuis Gusto2b (93) jusqu’à Gusto4 (2001), pts Berger, JAMA 2009;302:874-82

5 Women fare worse than men after acute MI
Women admitted for acute MI have % higher mortality at 30 days, as compared with men. This over-mortality is reduced after adjustment for age and co-morbidities. Sex-age interaction : discrepancy between studies Sex-Type of MI interaction : STEMI ≠ NSTEMI Women receive fewer treatments and no difference in mortality is observed after adjustment for co-morbidities and treatments Medicare, patients, pas de transferts, admis entre 94 et 95 Gan, N Engl J Med 2000;343:8-15

6 Aim of the Study Women fare worse than men after acute MI
Women admitted for acute MI have % higher mortality at 30 days, as compared with men. This over-mortality is reduced after adjustment for age and co-morbidities. Sex-age interaction : discrepancy between studies Sex-Type of MI interaction : STEMI ≠ NSTEMI Women receive fewer treatments and no difference in mortality is observed after adjustment for co-morbidities and treatments Aim of the Study To assess the effects of Clinical Characteristics and Treatments on Gender Difference , using a Propensity Score-Matched Analysis. CRUSADE entre 2000 et 2002

7 Methods All consecutive patients admitted between January 2006 and December 2007 CARDS dataset, dedicated team of data managers. Endpoint: 30 day all-cause mortality Use of matched pairs comparison: Two Propensity scores for being male by logistic regression, PS#1 with baseline characteristics (16 variables) PS#2 with baseline characteristics and treatments 1:1 matching on best 8 digits of the propensity score (match allowed for PS<0.015) 30 day mortality (Kaplan Meier curves and Odds ratios from conditional logistic regression) in unadjusted and matched cohorts Interactions : age, type of MI by Breslow-Day test.

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 Age (SD) 74 (13) 64 (13)  18.9 Diabetes 301 (27) 495 (21) 16.7 Hypertension 762 (68) 1143 (48) 12.7 Hypercholesterolemia 451 (40) 1132 (47) 15.9 Smoker 258 (23) 1583 (66) 56.7 Previous MI 151 (13) 449 (19) 15.2 Previous angioplasty 94 (8) 349 (15) 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) 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) 4.0 Admission Systolic BP 134 (29) 130 (28) 0.79 0.09 Killip class >2 94 (8) 127 (5) 12.3 Cardiogenic shock 48 (4) 94 (4) 0.61 0.25 GRACE risk score 147 [124 ;167] 132 [110 ;152] Admission Glucose 7 (4.4) 6.7 (3.5) 0.0035 2.99 BNP 480 [180;1202]  217 [83;544] Hs-CRP 8 [3;27] 6 [2;22] 

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) 133 GPIIbIIIa inhibitors (NSTEMI) 271 (40) 682 (53)  25.9 Reperfusion (STEMI) 281/461 (61) 843/1117 (75) 30.5 Primary PCI (STEMI) 215/461 (47) 615/1117 (55) 19.0 Thrombolysis (STEMI) 66/461 (14) 228/1117 (20) <0.009 8.0 Aspirin 1089 (97) 2360 (99) 16.8 Clopidogrel 1035 (92) 2290 (96) 25.0 Aspirin + Clopidogrel 31.8 ACEI / ARB 667 (60) 2052 (86) 23.9 Betablockers 791 (71) 1847 (77) 17.5 Statins 982 (88) 2296 (96) 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 Propensity score 1 (being male) with baseline characteristics Propensity score 2 (being male) with baseline characteristics and treatments Matching on propensity score 1 = 649 pairs Matching on propensity score 2 = 584 pairs Comparison of mortality Comparison of treatments Comparison of mortality

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

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

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

15 KM Cumulative mortality
Unmatched n= p=0.001 Matched #1 n=649 pairs p=0.23 Matched #2 n=584 pairs p=0.95 Log-Rank test: p=0.95 Days At risk Women Men Unmatched n= p=0.001 Matched #1 n=649 pairs p=0.23 Unmatched n= p=0.001

16 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 with type of MI
Women Men Women Men STEMI NSTEMI

18 Interaction with age ≥68 years <68 years P=0.04 P=0.01 P=0.29 Women

19 Discussion Matching on propensity score with analysis by pairs
Differences in characteristics, treatments and mortality Significant interaction with age: gender difference in older patients, disapears after matching. No significant interaction with the type of MI: higher mortality in women with STEMI, disappears after matching Sex differences in aspirin, clopidogrel, betablockers, ACEI and statins are explained by characteristics. Sex differences in coronary angiography and reperfusion in STEMI are not explained by characteristics No difference in mortality after matching on characteristics and treatments. Rosengren Eur Heart J 2001; 22: 314–322, Milcent Circulation. 2007;115: Blomkalns, CRUSADE, JACC 2005;45:832-7 Austin, Use of PS.., Stat Med 2005 Vaccarino, New Engl J Med 1999 Berger, JAMA 2009;302:874-82

20 Conclusions As compared with men, women admitted for acute MI receive fewer effective treatments and have a twofold higher 30 day mortality. Comparison of cohorts matched on baseline characteristics shows that co-morbidities explain the lower use of treatments. Nevertheless, women are less often submitted to coronary angiography and reperfusion (STEMI) and have a higher in-hospital mortality. Comparison of cohorts matched on baseline characteristics and treatments shows similar in-hospital and 30 day mortality between genders, suggesting that a higher use of invasive procedures and reperfusion strategy could reduce the difference in mortality.


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