Keith Dawkins MD FRCP FACC Southampton University Hospital UK Is Primary Angioplasty Equally Effective in Both Men and Women ?

Conflicts of Interest Research Grant Support Boston Scientific Corporation Advisory Board/Consultant Abbott Vascular Boston Scientific Corporation Conor Medsystems Eli Lilly Medtronic Nycomed

Women in Cardiology Women in Cardiology England, Wales & N. Ireland (RCP Census) Heart 2005;91: Consultant Cardiologists (n)

Establish mentors for women in cardiology Encourage flexible training Establish more part-time posts Improve 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: Old

Are we following the flock…? Women are poorly represented in cardiology Women with cardiac disease are under investigated and under treated Most cardiologists are men All men are bastards…

Deaths by Cause (Women) 2004 Office of National Statistics (2005) Scotland General Register Office (2005) Northern Ireland General Register Office (2005) CHD (15%) CVA (12%)Other CVD (9%) Lung Ca (4%) Breast Ca (4%) Colorectal Ca (2%) Other Ca (14%) Respiratory Disease (14%) Injuries & Poisoning (3%) All Other Causes (22%)

Age-Standardised Coronary Events (Women yrs) MONICA Project Lancet 1999;353: Coronary Events/100,000 population UK Glasgow UK Belfast

Acute Myocardial Infarction (ISIS-3) Age at Presentation Percent (%) NEJM 1998;338:8-14 p<0.001

AMI: Cumulative Mortality ( Day 0-35) NEJM 1998;338:8-14 Mortality (%) Days after Study Entry Women (n=6,600) Men (n=26,480) 9.1% 14.8% CI: 1.73 [ ]

Plaque-fissure and intracoronary thrombus MJ Davies

Ruptured plaque-fissure

Acute myocardial infarction (transmural)

Complications of acute myocardial infarction Papillary Muscle Rupture VSD LV Rupture

Infarct Vessel Patency and Mortality GUSTO-I angiographic trial Mortality at 30 days (%) Infarct vessel patency at 90 minutes TIMI-0 TIMI-1 TIMI-2 TIMI-3 Circ 1998;97:

Long-term survival after randomisation to Streptokinase: influence of myocardial blood flow JACC 1999;34:62-69 Mortality (%) Infarct vessel patency at 3-4 weeks TIMI-0/1 TIMI-2 TIMI-3 p=0.005 p= years 12 years

AHJ 2004;147: x Small numbers No gender matched controls Post hoc Sub-analysis Underpowered etc

Effect of Door-to-Balloon Time on Mortality: NRMI 3-4 (n=29,222) JACC 2006;47: Door-to-Balloon Time (mins) ≤90> > > In-Hospital Mortality (%) No Risk Factors

JACC 2006;47: Door-to-Balloon Time (mins) ≤90> > > In-Hospital Mortality (%) No Risk Factors ≥1 Risk Factors Effect of Door-to-Balloon Time on Mortality: NRMI 3-4 (n=29,222)

STEMI (NIRMI 3-4) Gender Prelevance (n=29,222) Prelevance (n) 70.9% 29.1% MaleFemale JACC 2006;47:

Door-to-Balloon Time (mins) Mortality (%) Male Female % 6.9% p< STEMI (NIRMI 3-4) Gender Differences (n=29,222)

PPCI: Relationship between Door-to-Balloon time and Gender Percentage (%) 3.9% 7.3% Male Female JAMA 2000;283: % 9.9% Male Female p=0.05 ≤2 hours >2 hours

Sex-Based Differences in Early Mortality of Patients undergoing Primary Angioplasty for First Acute Myocardial Infarction Circ 2001;104: Variable Women N=317 Men N=727 In-Hospital Mortality 7.9%2.3% Unadjusted OR [95% CI] 3.58 [ ]1.00 OR adjusted for age [95% CI] 2.47 [ ]1.00 OR adjusted for age and medical history [95% CI] 2.69 [ ]1.00 OR adjusted for age, medical history, time to treatment, and haemodynamic status [95% CI] 2.33 [ ]1.00

Prognosis after Myocardial Infarction Prognosis may be worse in women per se Women are older at the time of presentation Women may have more co-morbidity (e.g. shock, hypertension, obesity, renal impairment, diabetes) Women present later and delay seeking medical attention Women are under investigated Women are under treated (less lysis, PCI or CABG)

Physicians recommendations for Cardiac Catheterization: Effects of Race and Gender NEJM 1999;340: Variable Odds Ratio [95% CI] P Value Male Female [ ] 0.02 White Black [ ] 0.02

Gender Differences in Revascularisation Rates following AMI AJC 2006;97: Revascularisation Rate (%) MaleFemale 32% 20% p<0.001 Mortality (%) MaleFemale 9.6% 14.5% p<0.001

Admission Patterns and Revascularisation Rates following AMI AJC 2006;97: Revasc Rate in HREV +ve hospitals (%) MaleFemale 60% 54% p<0.001 Patients admitted HREV +ve (%) MaleFemale 52% 45% p<0.001

Age-adjusted in-hospital mortality with STEMI Men vs. Women AJC 2006;97: Odds Ratio [95% CI] All Patients Patients in HREV +ve Patients in HREV –ve Patients REV +ve Patients REV -ve Women Fare Better Men Fare Better

Failure of perfusion with thrombolytics alone… Failure of perfusion with thrombolytics alone… RCA occlusion LAD occlusion

Coronary Reperfusion Fibrinolysis vs. Percutaneous Intervention Heart 2002;88: >90% Availability <50% Treated 54% TIMI 3 10% Reocclusion 1% CVA 25% Late Occlusion Fibrinolysis 100% 50% 0% PCI 10%Availability 5% Reocclusion 0.1% CVA >90% Treated >90% TIMI 3

STEMI (PPCI vs. Thrombolysis) Short-term Outcome Lancet 2003;361:13-20 Death (Non-shock) Non-fatal AMI Stroke Combined p= p= p<0.0001p= p< Frequency (%) Gender?

Clinical Benefits of Abciximab is Independent of Gender EPIC, EPILOG, EPISTENT meta-analysis (n=6,595) JACC 2000;36: Patients %) MaleFemale p<0.001 Bleeding with Abciximab Major Bleed Minor Bleed Event Rate (%) Male Female 11.3% 12.7% p< % 5.8% p<0.001 Death, MI, TVR (30 Day) Abciximab Placebo

CADILLAC: Gender based Outcomes Circ 2005;111: STEMI <12 hrs, No shock (N=2,681) Angiographic Criteria fulfilled N=2,082 (73% men, 27% women) Randomise Primary PCI (N=518) Men = 370 Women = 148 Primary PCI + Abciximab (N=528) Men = 391 Women = 137 Multilink Stent (N=512) Men = 371 Women = 141 Multilink Stent + Abciximab (N=524) Men = 388 Women = 136

CADILLAC: Determinants of One Year Mortality Multivariate Predictors OR 95% CIP Female Gender Age < Killip Class 2/ Final TIMI Pre-TIMI Insulin treated DM Sx to procedure Start LAD vessel (vs. others) # Diseased vessels Circ 2005;111:

CADILLAC: Baseline Variables Multivariate Predictors Men Women P Number Chest pain to ER (hrs) 2.6 ± ± 2.6<0.001 ER to procedure (hrs) 1.9 ± ± 2.3<0.001 Stent Use 57% NS Abciximab Use 54%51%NS Circ 2005;111:

CADILLAC: Multivariate Predictors of One Year Mortality in Women Circ 2005;111: Multivariate Predictors OR 95% CIP Final MBG 0/ Final TIMI 0/ Creatinine Age (yrs) Hypertension

Conclusions: AHA Scientific Statement There is a rising mortality burden in women with CVD PCI is performed less frequently and with greater delays in women Better understanding of this disparity should be a priority RCTs should be developed to specifically assess gender-based, ethnic and racial results of interventional therapy with appropriately matched controls Circ 2005;111:

Why do women fare less well after Percutaneous Coronary Interventions? Increased peri-procedural complications Vascular access Bleeding Coronary dissection Abrupt vessel closure Oestrogen status Use of IIb/IIIa antagonists Smaller body habitus Women are older at the time of presentation Co-morbidity Diabetes mellitus Renal dysfunction

Conclusions: Mortality from STEMI is higher in women Women present later for PPCI PPCI is performed less frequently in women Outcomes following PPCI are less favourable in women Complications of PPCI are higher in women Present gender specific data are inadequate

XX Time for the Ladies to stop selling themselves short…

No more heads in the sand…