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.
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
1. Women admitted for acute MI have 40-100% higher mortality at
30 days, as compared with men. This over-mortality is reduced
after adjustment for age and co-morbidities.
Malacrida, ISIS-3, N Engl J Med 1998;338:8-14

3. Women fare worse than men after acute MI
1. Women admitted for acute MI have 40-100% higher mortality at
30 days, as compared with men. This over-mortality is reduced
after adjustment for age and co-morbidities.
2. Sex-age interaction : discrepancy between studies
Greater difference with older age Decrease in difference with age
Malacrida, N Engl J Med 1998;338:8-14 Vaccarino, N Engl J Med 1999;341:217-25

4. Women fare worse than men after acute MI
1. Women admitted for acute MI have 40-100% higher mortality at
30 days, as compared with men. This over-mortality is reduced
after adjustment for age and co-morbidities.
2. Sex-age interaction : discrepancy between studies
3. Sex-type of MI interaction : STEMI ≠ NSTEMI
Berger, JAMA 2009;302:874-82

5. Women fare worse than men after acute MI
1. Women admitted for acute MI have 40-100% higher mortality at
30 days, as compared with men. This over-mortality is reduced
after adjustment for age and co-morbidities.
2. Sex-age interaction : discrepancy between studies
3. Sex-Type of MI interaction : STEMI ≠ NSTEMI
4. Women receive fewer treatments and no difference in mortality
is observed after adjustment for co-morbidities and treatments
Gan, N Engl J Med 2000;343:8-15

6. Women fare worse than men after acute MI
1. Women admitted for acute MI have 40-100% higher mortality at
30 days, as compared with men. This over-mortality is reduced
after adjustment for age and co-morbidities.
2. Sex-age interaction : discrepancy between studies
3. Sex-Type of MI interaction : STEMI ≠ NSTEMI
4. 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.

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 (STEMI vs NSTEMI).

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 133
552(49) 1662(69) <0.0001
GPIIbIIIa inhibitors (NSTEMI) 271 (40) 682 (53) <0.0001 25.9
Reperfusion (STEMI) 281/461 (61) 843/1117 (75) 30.5
<0.001
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
Propensity score 1 (being male) Propensity score 2 (being male)
with baseline characteristics with baseline characteristics
and treatments
Matching on propensity score 1 Matching on propensity score 2
= 649 pairs = 584 pairs
Comparison of treatments Comparison of mortality
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
Women
Men
Log-Rank test: p=0.95
Unmatched n=3510 p=0.001
Matched #1 n=649 pairs p=0.23
Matched #2 n=584 pairs p=0.95
Days
0 5 10 20
30
At risk
584 574 565 544
529

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]
0.5 0.8 1 1.5 2 4
Odds ratios for men versus women

17. Sub-groups (1)
Interaction between Gender and type of MI
P=0.009
P=0.36
P=0.13
Mortality 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

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

19. Discussion
• Matching on propensity score with analysis by pairs
• Differences in characteristics, treatments and mortality
• Sex-age interaction : significant interaction with greater
gender difference in older patients, disappears after matching.
• Sex-type of MI interaction 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.
Milcent UseNewHeart J Med 1999 314–322, Berger, JAMA 2009;302:874-82
Vaccarino, EurPS.., 2007;115:833-839
Rosengren CRUSADE, JACC 2005;45:832-7
Blomkalns, of Engl J 2001; 22:
Austin, Circulation. Stat Med 2005

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.