Keith Dawkins MD FRCP FACCKeith Dawkins MD FRCP FACCSouthampton University HospitalSouthampton University HospitalUKUK

Is Primary Angioplasty Equally Effective in Both Men and Women ?

Conflicts of InterestConflicts of InterestResearch Grant Support

Boston Scientific Corporation

Advisory Board/ConsultantAbbott VascularBoston Scientific CorporationConor MedsystemsEli LillyMedtronicNycomed

Women in CardiologyWomen in CardiologyEngland, Wales & N. Ireland (RCP Census)

0100200300400500600700

1993 1994 1995 1996 1997 1998 1999 2000 2001 2002

Women Men

Heart 2005;91:283-289Heart 2005;91:283-289

Cons

ulta

nt C

ardi

olog

ists (

n)

Establish mentors for women in cardiologyEncourage flexible trainingEstablish more part-time postsImprove access for women to popular specialities (e.g. coronary intervention)Refuse to tolerate sexism or gender based discrimination in the work place

Eur Heart J 2000;21:1135-1140Eur Heart J 2000;21:1135-1140

OldOld

Are we following the flock…?

Women are poorly represented in cardiologyWomen with cardiac disease are under investigated and under treated Most cardiologists are men All men are bastards…

Deaths by Cause (Women) Deaths by Cause (Women) 20042004

Office of National Statistics (2005)Office of National Statistics (2005)Scotland General Register Office (2005)Scotland General Register Office (2005)Northern Ireland General Register Office Northern Ireland General Register Office

(2005)(2005)

CHD (15%)CVA (12%)Other CVD (9%)

Lung Ca (4%)

Breast Ca (4%)

ColorectalCa (2%)

Other Ca (14%)

Respiratory Disease (14%) Injuries & Poisoning (3%)All Other Causes (22%)

Age-Standardised Coronary Events Age-Standardised Coronary Events (Women 35-64 yrs) MONICA Project(Women 35-64 yrs) MONICA Project

Lancet 1999;353:1547-1557 Lancet 1999;353:1547-1557

Coronary Events/100,000 population

UK GlasgowUK GlasgowUK BelfastUK Belfast

0 50 100 150 200 250 300

Acute Myocardial Infarction (ISIS-3)Acute Myocardial Infarction (ISIS-3)

0

10

20

30

40

<50 50- 59 60- 69 70- 79 >79

Male Female

Age at Presentation

Perc

ent (

%)

NEJM 1998;338:8-14NEJM 1998;338:8-14

p<0.001

AMI: Cumulative Mortality (AMI: Cumulative Mortality (Day 0-Day 0-35)35)

NEJM 1998;338:8-14NEJM 1998;338:8-14

Mor

talit

y (%

)M

orta

lity

(%)

15 -

10 -

5 -

0 -

Days after Study Entry0 7 14 21 28 35

Women (n=6,600)

Men (n=26,480)9.1%

14.8%

CI: 1.73 [1.61-1.86]

Plaque-fissure and intracoronary thrombus

MJ DaviesMJ Davies

Acute myocardial infarction (transmural)Acute myocardial infarction (transmural)

Complications of acute myocardial infarctionComplications of acute myocardial infarctionPapillary Muscle Rupture

VSD

LV Rupture

Infarct Vessel Patency and MortalityInfarct Vessel Patency and MortalityGUSTO-I angiographic trialGUSTO-I angiographic trial

02468

1012

Mor

talit

y at

30

days

(%)

Infarct vessel patency at 90 minutes

TIMI-0 TIMI-1 TIMI-2 TIMI-3

Circ 1998;97:1549-1556Circ 1998;97:1549-1556

Long-term survival after randomisation to Long-term survival after randomisation to Streptokinase: influence of myocardial blood Streptokinase: influence of myocardial blood flowflow

JACC 1999;34:62-69JACC 1999;34:62-69

0

20

40

60

Mor

talit

y (%

)

Infarct vessel patency at 3-4 weeksTIMI-0/1 TIMI-2 TIMI-3

p=0.005p=0.023

5 years 12 years

AHJ 2004;147:133-139AHJ 2004;147:133-139

xSmall numbersNo gender matched controlsPost hocSub-analysisUnderpowered etc

Effect of Door-to-Balloon Time on Effect of Door-to-Balloon Time on Mortality: Mortality: NRMI 3-4 NRMI 3-4 (n=29,222)(n=29,222)

JACC 2006;47:2180-2186JACC 2006;47:2180-2186

Door-to-Balloon Time (mins)≤90 >90-120 >120-150 >150

12 -

10 -

8 -

6 -

4 -

2 -

0

In-H

ospi

tal M

orta

lity

(%) No Risk Factors

JACC 2006;47:2180-2186JACC 2006;47:2180-2186

Door-to-Balloon Time (mins)≤90 >90-120 >120-150 >150

12 -

10 -

8 -

6 -

4 -

2 -

0

In-H

ospi

tal M

orta

lity

(%) No Risk Factors

≥1 Risk Factors

Effect of Door-to-Balloon Time on Effect of Door-to-Balloon Time on Mortality: Mortality: NRMI 3-4 NRMI 3-4 (n=29,222)(n=29,222)

STEMI (NIRMI 3-4)STEMI (NIRMI 3-4)Gender Prelevance Gender Prelevance (n=29,222)(n=29,222)

0

5000

10000

15000

20000

25000

Prel

evan

ce (n

) 70.9%

29.1%

Male Female

JACC 2006;47:2180-2186JACC 2006;47:2180-2186

JACC 2006;47:2180-2186JACC 2006;47:2180-2186

90

95

100

105

110

0

2

4

6

8

10

Door

-to-B

allo

on T

ime

(min

s)

Mor

talit

y (%

)

Male MaleFemale Female

100

108

3.6%

6.9%

p<0.0001 p<0.0001

STEMI (NIRMI 3-4)STEMI (NIRMI 3-4)Gender Differences Gender Differences (n=29,222)(n=29,222)

PPCI: PPCI: Relationship between Door-to-Balloon Relationship between Door-to-Balloon time and Gendertime and Gender

0

5

10

15

Perc

enta

ge (%

)

3.9%7.3%

Male Female

JAMA 2000;283:2941-2947JAMA 2000;283:2941-2947

6.5%

9.9%

Male Female

p=0.05 p=0.05

≤2 hours >2 hours

Sex-Based Differences in Early Mortality of Sex-Based Differences in Early Mortality of Patients undergoing Primary Angioplasty for Patients undergoing Primary Angioplasty for First Acute Myocardial InfarctionFirst Acute Myocardial Infarction

Circ 2001;104:3034-3038Circ 2001;104:3034-3038

Variable WomenN=317

Men N=727

In-Hospital Mortality 7.9% 2.3%Unadjusted OR [95% CI] 3.58 [1.9-6.7] 1.00

OR adjusted for age [95% CI] 2.47 [1.3-4.7] 1.00OR adjusted for age and medical history [95% CI] 2.69 [1.4-5.2] 1.00

OR adjusted for age, medical history, time to treatment, and haemodynamic status [95% CI]

2.33 [1.2-4.6] 1.00

Prognosis after Myocardial InfarctionPrognosis after Myocardial Infarction

Prognosis may be worse in women per se

Women are older at the time of presentationWomen may have more co-morbidity (e.g. shock, hypertension, obesity, renal impairment, diabetes)Women present later and delay seeking medical attentionWomen are under investigatedWomen are under treated (less lysis, PCI or CABG)

Physicians recommendations for CardiacPhysicians recommendations for CardiacCatheterization: Effects of Race and GenderCatheterization: Effects of Race and Gender

NEJM 1999;340:618-626NEJM 1999;340:618-626

Variable Odds Ratio [95% CI] P ValueMaleFemale

1.00.6 [0.4-0.9] 0.02

WhiteBlack

1.00.6 [0.4-0.9] 0.02

Gender Differences in Gender Differences in Revascularisation Rates following AMIRevascularisation Rates following AMI

AJC 2006;97:1722-1726AJC 2006;97:1722-1726

0

10

20

30

40

50

Reva

scul

arisa

tion

Rate

(%)

Male Female

32%

20%

p<0.001

0

5

10

15

20

Mor

talit

y (%

)

Male Female

9.6%

14.5%p<0.001

Admission Patterns and Admission Patterns and Revascularisation Rates following AMIRevascularisation Rates following AMI

AJC 2006;97:1722-1726AJC 2006;97:1722-1726

0

10

20

30

40

50

60

70

Reva

sc R

ate

in H

REV

+ve

hosp

itals

(%)

Male Female

60%54%

p<0.001

0

10

20

30

40

50

60

70

Patie

nts a

dmitt

ed H

REV

+ve

(%)

Male Female

52%45%

p<0.001

Age-adjusted in-hospital mortality with STEMIAge-adjusted in-hospital mortality with STEMIMen Men vs.vs. Women Women

AJC 2006;97:1722-1726AJC 2006;97:1722-1726

0 0.5 1.0 1.5 1.75

Odds Ratio [95% CI]

All PatientsAll PatientsPatients in HREV +vePatients in HREV +vePatients in HREV –vePatients in HREV –ve

Patients REV +vePatients REV +vePatients REV -vePatients REV -ve

Women Fare BetterWomen Fare Better Men Fare BetterMen Fare Better

Failure of perfusion with thrombolyticsalone…

RCA occlusion LAD occlusion

Coronary ReperfusionCoronary ReperfusionFibrinolysis Fibrinolysis vs.vs. Percutaneous Intervention Percutaneous Intervention

Heart 2002;88:298-305Heart 2002;88:298-305

>90% Availability

<50% Treated

54% TIMI 3

10% Reocclusion

1% CVA

25% LateOcclusion

Fibrinolysis100%

50%

0%

PCIPCI

10% Availability 5% Reocclusion

0.1% CVA

>90% Treated

>90% TIMI 3

STEMI (PPCI STEMI (PPCI vs.vs. Thrombolysis) Thrombolysis)Short-term OutcomeShort-term Outcome

0

4

8

12

16Primary PCI Lysis

Lancet 2003;361:13-20Lancet 2003;361:13-20

Death Death(Non-shock)

Non-fatalAMI

Stroke Combined

p=0.0002 p=0.0003 p<0.0001 p=0.0004

p<0.0001

Freq

uenc

y (%

)

Gender?Gender?

Clinical Benefits of Abciximab is Clinical Benefits of Abciximab is Independent of GenderIndependent of GenderEPIC, EPILOG, EPISTENT meta-analysis (n=6,595)EPIC, EPILOG, EPISTENT meta-analysis (n=6,595)

JACC 2000;36:381-386JACC 2000;36:381-386

2.2

6.71.3

3.0

0

2

4

6

8

10

12

Patie

nts %

)

Male Female

p<0.001

Bleeding with Abciximab

Major BleedMinor Bleed

0

5

10

15

20

Even

t Rat

e (%

)

Male Female

11.3%12.7%

p<0.001

6.5%5.8%

p<0.001

Death, MI, TVR (30 Day)

Abciximab Placebo

CADILLAC: CADILLAC: Gender based OutcomesGender based Outcomes

Circ 2005;111:1611-1618Circ 2005;111:1611-1618

STEMI <12 hrs, No shock (N=2,681)STEMI <12 hrs, No shock (N=2,681)

Angiographic Criteria fulfilledAngiographic Criteria fulfilledN=2,082N=2,082

(73% men, 27% women)(73% men, 27% women)

Randomise

Primary PCIPrimary PCI(N=518)(N=518)

Men = 370Men = 370Women = 148Women = 148

Primary PCIPrimary PCI+ Abciximab+ Abciximab

(N=528)(N=528)Men = 391Men = 391

Women = 137Women = 137

Multilink StentMultilink Stent(N=512)(N=512)

Men = 371Men = 371Women = 141Women = 141

Multilink StentMultilink Stent+ Abciximab+ Abciximab

(N=524)(N=524)Men = 388Men = 388

Women = 136Women = 136

CADILLAC:CADILLAC: Determinants of One Year Determinants of One Year MortalityMortality

Multivariate Predictors OR 95% CI PFemale Gender 1.77 1.03-3.04 0.037Age 1.06 1.03-1.09 <0.0001Killip Class 2/3 2.24 1.19-4.20 0.0003Final TIMI 3 0.54 0.31-0.93 0.007Pre-TIMI 3 0.68 0.53-0.87 0.012Insulin treated DM 2.70 1.03-7.11 0.012

Sx to procedure Start 1.07 1.01-1.11 0.031

LAD vessel (vs. others) 2.38 1.39-4.07 0.035

# Diseased vessels 1.54 1.10-2.16 0.019

Circ 2005;111:1611-1618Circ 2005;111:1611-1618

CADILLAC:CADILLAC: Baseline Variables Baseline Variables

Multivariate Predictors Men Women PNumber 1520 562 ---Chest pain to ER (hrs) 2.6 ± 2.5 3.0 ± 2.6 <0.001ER to procedure (hrs) 1.9 ± 2.2 2.1 ± 2.3 <0.001Stent Use 57% 57% NSAbciximab Use 54% 51% NS

Circ 2005;111:1611-1618Circ 2005;111:1611-1618

CADILLAC:CADILLAC: Multivariate Predictors of One Multivariate Predictors of One Year Mortality in WomenYear Mortality in Women

Circ 2005;111:1611-1618Circ 2005;111:1611-1618

Multivariate Predictors OR 95% CI PFinal MBG 0/1 5.15 1.98-13.41 0.0008Final TIMI 0/1 10.47 1.09-100.40 0.0042Creatinine 3.87 1.86-8.02 0.0003Age (yrs) 1.09 1.04-1.14 0.0006Hypertension 4.31 1.24-14.95 0.0212

Conclusions: Conclusions: AHA Scientific StatementAHA Scientific Statement

There is a rising mortality burden in women with CVDPCI is performed less frequently and with greater delays in womenBetter understanding of this disparity should be a priorityRCTs should be developed to specifically assess gender-based, ethnic and racial results of interventional therapy with appropriately matched controls

Circ 2005;111:940-953Circ 2005;111:940-953

Conclusions:Conclusions:

Mortality from STEMI is higher in womenWomen present later for PPCIPPCI is performed less frequently in womenOutcomes following PPCI are less favourable in womenComplications of PPCI are higher in womenPresent gender specific data are inadequate

XXXX

Time for the Ladies to stop Time for the Ladies to stop selling themselves short…selling themselves short…

No more heads in the sand…No more heads in the sand…