keith dawkins md frcp facc southampton university hospital uk is primary angioplasty equally...
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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
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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…