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

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

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

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

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

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 ≠ NSTEMI4. 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

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 ≠ NSTEMI4. Women receive fewer treatments and no difference in mortality

is observed after adjustment for co-morbidities and treatments

To assess the effects of Clinical Characteristics and Treatments on Gender Difference ,

using a Propensity Score-Matched Analysis.

Aim of the Study

Women fare worse than men after acute MI

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.

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

Baseline characteristics (1)

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

Baseline characteristics (2)

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 1035 (92) 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

In-hospital Treatments

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 treatmentsComparison 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

Effect of matching on sex differences

P values for the difference between men and women

Unmatched dataset

0.05

Effect of matching on sex differences

P values for the difference between men and women

Unmatched dataset Matched #1 dataset

0.05

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

KM Cumulative mortality

Unmatched n=3510 p=0.001Unmatched n=3510 p=0.001Matched #1 n=649 pairs p=0.23

Log-Rank test: p=0.95

Days0 5 10 20

30At risk584 574 565 544

529584 573 562 550

530

WomenMen

Unmatched n=3510 p=0.001Matched #1 n=649 pairs p=0.23Matched #2 n=584 pairs p=0.95

0.5 0.8 1 1.5 2 4

Aspirinunmatched OR= 1.35 [1.06; 1.80]Matched #1 OR= 1.10 [0.46; 2.62]Clopidogrelunmatched OR= 1.65 [1.38; 2.01]Matched #1 OR= 1.04 [0.58; 1.84]Aspirin and Clopidogelunmatched OR= 1.67 [1.40; 2.01]Matched #1 OR= 1.10 [0.46; 1.63]ACEI or ARBunmatched OR= 1.42 [1.24; 1.65]Matched #1 OR= 1.29 [0.97; 1.70]Beta blockerunmatched 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 Angiographyunmatched OR= 2.82 [2.40; 3.41]Matched #1 OR= 1.57 [1.10; 2.18]Reperfusion /PPCIunmatched OR= 1.56 [1.29; 1.89]Matched #1 OR= 1.24 [1.12; 1.71]Reperfusion /FLunmatched OR= 1.82 [1.24; 2.12]Matched #1 OR= 1.72 [1.08; 2.73]

In-Hospital mortalityunmatched 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 mortalityunmatched 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

Interaction with type of MI

P=0.15

P=0.24

P=0.10

STEMI NSTEMIWomenMen

WomenMen

Interaction with age

<68 years ≥68 years

WomenMen

WomenMen

P=0.04

P=0.01

P=0.29

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.Vaccarino, New Engl J Med 1999 Austin, Use of PS.., Stat Med 2005 Berger, JAMA 2009;302:874-82 Blomkalns, CRUSADE, JACC 2005;45:832-7 Rosengren Eur Heart J 2001; 22: 314–322,Milcent Circulation. 2007;115:833-839

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.