# Presentation: 489223

## Cardiovascular Disease in WomenModule V: Prognosis and Treatment Outcomes

## Women Receive Less Interventions to Prevent and Treat Heart Disease

**Less cholesterol screening**
**Less lipid-lowering therapies**
**Less use of heparin, beta-blockers and aspirin during myocardial infarction**
**Fewer referrals to cardiac rehabilitation**

**      ****Source:  **Chandra 1998, Nohria 1998, Scott 2004, O’Meara 2004, Hendrix 2005

**Notes:**
SLIDE INFORMATION SOURCES:  Chandra NC, et al.  Observations of the treatment of women in the United States with myocardial infarction; a report from the National Registry of Myocardial Infarction-I. Arch Intern Med 1998; 158:981-988; Nohria A, et al. Gender differences in coronary artery disease in women: gender differences in mortality after myocardial infarction: why women fare worse than men. Cardiol Clin 1998; 16:45-57. Scott LB, Allen JK. Providers perceptions of factors affecting women’s referral to outpatient cardiac rehabilitation programs: an exploratory study. J Cardiopulm Rehab 2004; 24:387-391. O’Meara JG, et al.  Ethnic and sex differences in the prevalence, treatment, and control of dyslipidemia among hypertensive adults in the GENOA study. Arch Intern Med 2004; 164:1313-1318.  Hendrix KH, et al.  Ethnic, gender, and age-related differences in treatment and control of dyslipidemia in hypertensive patients. Ethn Dis 2005; 15:11-16.

## Prognosis After MI

**38% of women die within first year**
- Compared to 25% of men
**35% of women will have second MI within 6 years**
- Compared to 18% of men

**      ****Source:  **Wenger 2004

**Notes:**
SLIDE INFORMATION SOURCE:  Wenger NK.  Cardiovascular health and disease in women problems and prospects.  Circulation 2004; 109:558-560.

## Prognosis

**Women < 65 yrs have 2 X mortality rate after MI compared to men of same age**
**After MI, women have significantly higher rates of:**
- Depression
- Physical disability
**After CABG, women have significantly higher rates of:**
- Hospital readmission
- Reduced mental health and physical functioning

**      ****Source: **Vaccarino 1999, Ades 2002, Lauzon 2003, Vaccarino 2003

**Notes:**
SLIDE INFORMATION SOURCE:  Vaccarino V, et al.  Sex-based differences in early mortality after myocardial infarction.  N Engl J Med 1999. 341:217-225. ; Ades PA, et al.  Determinants of disability in older coronary patients.  Am Heart J 2002. 143:151-156.  Lauzon C, et al.   Depression and prognosis following hospital admission because of acute myocardial infarction.  CMAJ 2003. 168:547-552, Vaccarino V, et al.  Sex differences in health status after coronary artery bypass surgery. Circulation 2003; 108:2642-2647.

## Undertreatment of MI in Women

**Compared with men:**
- Less emergent thrombolysis
- Less acute catheterization and angioplasty
- Less acute surgical revascularization
- Less use of heparin, beta-blockers, and aspirin

**      ****Source:  **Chandra 1998, Nohria 1998

**Notes:**
SLIDE INFORMATION SOURCES:  Chandra NC, et al.  Observations of the treatment of women in the United States with myocardial infarction; a report from the National Registry of Myocardial Infarction-I. Arch Intern Med 1998. 158:981-988; Nohria A, et al.  Gender differences in coronary artery disease in women: gender differences in mortality after myocardial infarction: why women fare worse than men. Cardiol Clin 1998. 16:45-57.

## Cardiac Rehabilitation for Women

**Cardiac rehabilitation programs benefit both men and women**
**Participation rates for eligible women are 15-20%, compared to 25-31% for eligible men**
**Women are more likely to drop out after beginning cardiac rehabilitation**
**Healthcare providers are less likely to encourage rehabilitation for female patients**

**      ****Source: **Scott 2004

**Notes:**
SLIDE INFORMATION SOURCE: Scott LB, Allen JK. Providers perceptions of factors affecting women’s referral to outpatient cardiac rehabilitation programs: an exploratory study. J Cardiopulm Rehab 2004. 24:387-391.

## Benefits of ASA in Women with Established CAD

***  P = 0.002 **P = 0.0001**

- *

- **

**      ****Source: **Adapted from Harpaz 1996

**Notes:**
SLIDE INFORMATION SOURCE:  Harpaz D, et al.  Effect of aspirin on mortality in women with symptomatic or silent myocardial ischemia.  Am J Cardiol 1996; 78:1215-1219.

This graph shows results of a prospective cohort study of 2,418 women with CAD.  Aspirin use significantly decreased both CVD and overall mortality at 3 years of follow-up (1).
In the randomized ISIS-2 trial, aspirin use decreased 5-week vascular mortality in women by 16.5% compared to placebo (2).. 
An overview of randomized trials of antiplatelet therapies published before 1990 suggested that women with prior vascular events randomized to antiplatelet therapy had a 25% reduction in subsequent vascular events (3).  

(1) Harpaz D, et al.  Effect of aspirin on mortality in women with symptomatic or silent myocardial ischemia.  Am J Cardiol 1996; 78:1215-1219.
(2) ISIS-2 Collaborative Group. Randomized trial of intravenous streptokinase, oral aspirin, both, or neither. Lancet 1988; 8607:349-360.
(3) Antiplatelet Trialists’ Collaboration. Collaborative overview of randomized trials of antiplatelet therapies in various categories of patients.  BMJ 1994; 308:81-106.

## Addition of Clopidogrel to Aspirin and Fibrinolytic Therapy for MI with ST-Segment Elevation in Women

**P < 0.05; reduction in odds = 38%**

**Source:** Sabatine 2005

**Notes:**
SLIDE INFORMATION SOURCE:  Sabatine MS, et al.  Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med 2005. 352:1179-1189.

This study of 3491 patients included 688 women randomized to clopidogrel 300 mg loading dose followed by 75 mg daily or placebo until coronary angiography, hospital discharge, or hospital day 8, whichever occurred first. Patients also received a fibrinolytic agent, aspirin, and , when appropriate, heparin.  Women’s reduction in a composite endpoint of angiographic reocclusion, death, and recurrent MI before angiography was similar to men’s (1).
A previous study showed a statistically significant benefit to this regimen continued for 3-12 months in women with acute coronary syndromes without ST-segment elevation, also with a benefit similar to men (9.5% of women w. death from CVD, nonfatal MI or CVA compared to 10.7% for placebo) (2).

(1) Sabatine MS,  et al.  Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med 2005. 352:1179-1189.
(2) Yusuf S, et al.  Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001. 345:494-502.

## Gender Gap in Dyslipidemia Treatment

**Significantly more men than women have annual cholesterol measurements**
**Significantly more men than women receive effective lipid-lowering therapy**
**African Americans receive less lipid-lowering treatment compared to whites**

**      ****Source:  **O’Meara 2004, Hendrix 2005

**Notes:**
SLIDE INFORMATION SOURCES:  O’Meara JG, et al.  Ethnic and sex differences in the prevalence, treatment, and control of dyslipidemia among hypertensive adults in the GENOA study. Arch Intern Med 2004. ;164:1313-1318.  Hendrix KH, et al.   Ethnic, gender, and age-related differences in treatment and control of dyslipidemia in hypertensive patients. Ethn Dis 2005; 15:11-16.

## Meta-Analysis of 11 Clinical Trials of Statin Therapy Including 15,917 Women with Known CHD

**CHD Events**

**Non-Fatal MI**

**CHD Mortality**

**      ****Source: **Grady 2003.

**Notes:**
SLIDE INFORMATION SOURCE:  Grady D.  Diagnosis and treatment of coronary heart disease in women: systematic reviews of evidence on selected topics.  U.S. Department of Health and Human Services, Public Health Service, Agency for Healthcare Research and Quality, Evidence Report/Technology Assessment Number 81, 2003.

A meta-analysis of 11 clinical trials of lipid lowering therapy including 15,917 women with known CHD showed a 26% risk reduction for CHD mortality, a 36% risk reduction for  nonfatal MI, and a 21% reduction in CHD events (1).

(1)  Grady D.  Diagnosis and treatment of coronary heart disease in women: systematic reviews of evidence on selected topics.  U.S. Department of Health and Human Services, Public Health Service, Agency for Healthcare Research and Quality, Evidence Report/Technology Assessment Number 81, 2003.

## Simvastatin and Gender Risk for CHD and Mortality

***P <0.05**

**      ****Source: **Scandinavian Simvastatin Survival Study Group 1994

**Notes:**
SLIDE INFORMATION SOURCE:  Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)  Lancet. 1994.;344:1383-1389. 
The 4S trial (Scandinavian Simvastatin Survival Study) included 827 women w/ previous coronary events or angina randomized to simvastatin at escalating dosages or placebo.  All participants were encouraged to follow a lipid-lowering diet.  Over a 5.6 year period, women experienced a  35% risk reduction for major coronary events (1).

(1) Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)  Lancet. 1994; 344:1383-1389. 

## Heart Protection Study: Major Findings

**Randomized, placebo-controlled trial of over 20,000 patients at risk for CVD**
**Statin treatment reduced the risk of heart attacks and strokes by at least one third, as well as reducing the need for arterial surgery, angioplasty and amputations.**
**Major CV events were reduced in women (5082 enrolled) as well as men, and in all age groups, across all cholesterol levels.**

**      ****Source: **HPS Writing Group, Lancet 2002

**Notes:**
SLIDE INFORMATION SOURCE:  MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002. 360(9326):7-22.

## Primary Prevention of CHD Events with Statin Treatment: AFCAPS/TexCAPS

**Relative Risk of First Major Coronary Events**

**P < 0.001 compared to placebo**

**      ****Source: **Downs 1998

**Notes:**
SLIDE INFORMATION SOURCE:   Downs JR, et al.  Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS.  JAMA 1998; 279:1615-1622.

AFCAPS/TexCAPS was a randomized, double-blind, placebo-controlled primary prevention trial that included 6605 men and women and was conducted at 2 sites in Texas. The study included 997 postmenopausal women (1).
AFCAPS/TexCAPS was powered to investigate whether long-term lipid lowering with lovastatin would decrease the rate of first acute major coronary events compared with placebo during at least 5 years of follow-up in a cohort without clinical evidence of atherosclerotic cardiovascular disease and with average TC and LDL-C levels and below-average HDL-C levels (1). 

(1) Downs JR, Clearfield M, Weis S, et al.  Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS.  JAMA 1998; 279:1615-1622.

## Implanted Cardioverter Defibrillator (ICD) Therapy in Women

**Women appear to have a lower incidence of sudden cardiac death then men**
**Women present more frequently with ventricular fibrillation than men**
**Women have similar survival rates after ICD implantation compared to men **

**      ****Source:  **Pires 2002

**Notes:**
SLIDE INFORMATION SOURCE:  Pires LA, et al. Outcome of women versus men with ventricular tachyarrythmias treated with the implantable cardioverter defibrillator. J Cardiovasc Electrophysiol 2002. 13:563-568.

## Interventional Procedures and Surgery

**Higher complication and death rates**
- Smaller artery size
- More co-existing illnesses (older at presentation)
- Higher rates of diabetes
- More urgent and emergent presentations
- Higher incidence of congestive heart failure in women from diastolic dysfunction

**      ****Source:  **Jacobs 2003

**Notes:**
SLIDE INFORMATION SOURCE:  Jacobs AK.  Coronary revascularization in women in 2003: sex revisited.  Circulation 2003; 107:375-377.

## Coronary Revascularization in Women Compared to Men

**Increased use of PTCA compared to stents, because of smaller vessel size**
**Decreased rates of glycoprotein IIb/IIIa inhibitor use, possibly because of increased bleeding complications in women**
**Higher in-hospital mortality for CABG and PCI**
- Higher rates of vascular complications
- Higher transfusion rates

**      ****Source: **Jacobs 2003

**Notes:**
SLIDE INFORMATION SOURCE:  Jacobs AK.  Coronary revascularization in women in 2003: sex revisited.  Circulation 2003;107:375-377.

## Revascularization Outcomes in Women: Improvements in Recent Years

**NHLBI registry data shows improved clinical success rates and lower major complication rates for women undergoing PTCA**
**Retrospective data suggest that women have lower mortality rates when undergoing off-pump CABG, compared to standard CABG**

**      ****Source:  **Jacobs 1997, Petro 2000

**Notes:**
SLIDE INFORMATION SOURCES:  Jacobs AK, et al.  Documentation of decline in morbidity in women undergoing coronary angioplasty (a report from the 1993-94 NHLBI percutaneous transluminal coronary angioplasty registry). Am J Cardiol 1997; 80:979-984.  Petro KR, et al.  Minimally invasive coronary revascularization in women: a safe approach in a high risk group.  Heart Surg Forum 2000; 3:41-46.

## Sex Differences for In-Hospital Mortality After CABG: Higher Mortality in Younger Women

**P for interaction between  sex and age = 0.002.**

**≥**

**      ****Source: **Adapted from Vaccarino 2002

**Notes:**
SLIDE INFORMATION SOURCE:: Vaccarino V, et al.  Sex differences in hospital mortality after coronary artery bypass surgery: evidence for a higher mortality in younger women.  Circulation 2002; 105(10): 1176-1181.

Data was available for 51 187 patients (30% women) included in the National Cardiovascular Network database who received CABG b between October 1993 and December 1999 (1). 
In all age groups  women had higher left ventricular ejection fraction and fewer diseased vessels (1). 
Women had higher in-hospital mortality rates than men, but sex differences in mortality were more marked among younger patients. Women <50 years of age were 3 times more likely to die than men (3.4% versus 1.1%), and women 50 to 59 years of age were 2.4 times more likely to die than men (2.6% versus 1.1%). In the older age categories, the sex difference in in-hospital mortality was less marked (P<0.001 for the interaction between sex and age)(1). Adjustment for preoperative risk factors only slightly decreased the strength of this interaction (1). 

(1) Vaccarino V, et al.  Sex differences in hospital mortality after coronary artery bypass surgery: evidence for a higher mortality in younger women.  Circulation 2002. 105(10): 1176-1181.

## CABG Outcomes in Women: A Vicious Cycle

**Perception: Higher post-operative morbidity/mortality in women**

**Prompt referral for CABG discouraged in women**

**Women referred at later stages ****of disease, w/ more comorbidities**

**Higher operative risk for women**

**Fewer long-term benefits for women**

**      ****Source:  **Adapted from Vaccarino 2003

- Final May 2006

**Notes:**
SLIDE INFORMATION SOURCE:  Vaccarino V, Zhen QL, Stanislav VK, et al.  Sex differences in health status after coronary artery bypass surgery. Circulation 2003; 108:2642-2647.