Gender Differences in Cardiovascular Disease - Society for ...

Gender Differences in
Cardiovascular
Disease
Susan K. Bennett, MD, FACC
Director, Women’s Women s Heart Program
George Washington University Hospital

1990
2006
History of Women in Clinical
Trials
�� Protectionism and Exclusion
�� 1993- 1993 NIH Health and Revitalization Act
“imperative imperative to determine whether intervention or
therapy being studied affects women differently”
differently
�� Equality through Single-Sex Single Sex Studies
�� PEPI, HERS, WHI, Nurses Health Study
�� Scientific Determination that Drugs/Devices
are Safe and Effective in Men and Women

Notable Achievements for Women and
Cardiovascular Disease
�� Women’s Women s Health Initiative (WHI)
�� “Lauded Lauded despite its Contrariness”
Contrariness
�� Hormone therapy (Premarin ( Premarin and Prempro) Prempro
�� Did not reduce heart attacks and strokes
�� Low fat diet did not reduce CV events
�� Anti-oxidant Anti oxidant vitamins did not reduce CV events
�� Women and Ischemic Syndromes (WISE)
�� Coronary artery disease can be different for women
�� More small vessel disease, microvascular angina
�� The Heart Truth Campaign

Working to Improve the Lives of Women!
American Heart Association

Awareness of Heart Disease as the
#1 Killer of American Women
(General Female Population)
% of women aware
60
50
40
30
20
10
0
30
34
46
55
1997 2000 2003 2005
Based on serial American Heart Association Surveys

Awareness of Heart Disease as the
#1 Killer of American Women
(Female Population by Race)
% of women aware
70
60
50
40
30
20
10
0
38
Circulation. 2006:113:525-534
34
43
62
black hispanic other white

Does Awareness Lead to Action?
�� Women who have seen, heard or read
about heart disease
�� Added more physical activity
�� Avoided unhealthy foods
�� Quit smoking
�� YES! Awareness leads to personal action!

Cardiovascular Disease Mortality
Trends for Males and Females
United States: 1979-2003*
1979 2003*
Deaths in Thousands
520
500
480
460
440
420
4000
79 80 85 90 95 00 03
Source: CDC/NCHS. * Preliminary
Years
Males Females

400,000
350,000
300,000
250,000
200,000
150,000
100,000
Leading Causes of Death for
50,000
0
American Women (2000)
366,000
Heart
Disease
103,000
Stroke
Source: The Healthy Heart Handbook for Women, NHLBI (2003)
65,000 62,000
Lung
Cancer
Causes of Death
COPD
42,000
Breast
Cancer

Compared with Men:
� 38% of women and 25% of men will die within
one year of a first recognized heart attack.
� 35% of women and 18% of men heart attack
survivors will have another heart attack within six
years.
.
� 46% of women and 22% of men heart attack
survivors will be disabled with heart failure within
six years.
� Women are almost twice as likely as men to die
after bypass surgery
Statistics complied from:
National Center on Health Statistics; National Heart, Lung and Blood Institute
American Heart Association's 2002 Heart and Stroke Statistical Update
which may be viewed online at: http://www.americanheart.org/downloadable/heart/10148328094661013190990123HS_State_02.pdf

Myths about Women and CVD
The Perception: "I hear more about women and heart
disease, but I really don’t don t see it in my practice” practice
The Environment: Unlike the community of women who
have been targeted with awareness messages,
physicians have not received medical education about
gender differences in the field of cardiology
The Reality: Health care providers have less knowledge
about women and heart disease than the community and
women are being treated differently contributing to a
worsening gender gap in care

Perception:
The Old Face of Heart Disease

Reality:
The New Face of Heart Disease

Awareness of Heart Disease as a Greater
Killer of American Women Than Men
(Physician Population by Specialty)
%
45
40
35
30
25
20
15
10
5
0
Basic Facts Seeking Knowledge
Mosca et al, 2005 Circulation 111:499
PCP
GYN
CARDS

Perception and Action
�� Physicians underestimate women’s women s risk
�� Perception of low risk leads to inaction
�� Uncontrolled high blood pressure
�� High cholesterol
�� Life Style change not stressed
Mosca et al, 2005 Circulation 111:499

Myths about Women and CVD
�� The Perception: “When When it comes to drugs and devices, I
don’t don t treat women any differently than men” men
�� The Environment: Pharmaceutical and Drug Device
companies and the FDA have made few (if any)
important recommendations about cardiovascular drugs
and devices that differ between men and women
�� The Reality: Women are being given drugs and devices
differently than men and we cannot assume that women
respond the same to cardiovascular drugs and devices
the same as men (we ARE different from womb to tomb)

Utilization of Procedures/Devices
Procedures in Thousands
1,400
1,200
1,000
800
600
400
200
0
40%
35%
men
women
cath PTCA stents CABG ICD
2001 data, American Heart Association. Heart Disease and Stroke Statistics – 2004 Update
35%
31% 20%

50
45
40
35
30
25
20
15
10
5
0
Representation of Women in RCT’s RCT of
Acute Coronary Syndromes
٭
Proportion of All Pt's with MI in the US
Proportion Enrolled in RCT's of MI
Proportion Enrolled in US RCT's of MI
1966-1970 1971-1980 1981-1990 1991-1995 1996-2000
*Proportion of all
patients with MI
based on Worcester
Heart Attack Study
Source: Lee et al,
JAMA 2001:268:708-
713

Ensuring Safety and Efficacy of
CV Drugs
�� FDA’s FDA s Office of Special Health Issues
�� “Race, Race, Age and Gender: A Review of
Demographic Subgroups in Clinical Trials of
FDA-Regulated FDA Regulated Drugs and Biologics” Biologics
�� 85% of IND protocols did not submit required data
analysis of safety and efficacy for sub-groups
sub groups

Ensuring Safety and Efficacy of
�� “Women Women’s s Participation in Clinical Trials
and Gender-Related Gender Related Labeling” Labeling (review of
New Molecular Entities Approved 1995- 1995
2000) published June 2001
�� 493,600 trial participants
�� 36% women
�� 38% male
�� 26% ???????
Drugs
Available at
http://www.fda.gov/cder/reports/womens_health/women_clin_trials.htm

Overall Participation by Gender in
Cardiovascular NDA’s NDA (N=461,267*)
66%
6%
* Excludes gender-specific products
28%
Women
Men
Unspecified

Medical Officer Findings
no comment
no analysis
conducted
data inadequate to
analyze gender effect
gender analysis not
applicable
no differences found
differences found
(185 reviews of drugs)
10
10
12
32
42
78
0 20 40 60 80 100
No. of Reviews
1/3 of all submissions

Summary
�� Education works in raising awareness
�� Apply to medical community
�� Apply to African American, Hispanic
populations
�� CVD trials must enroll population at risk
�� FDA must assure that drugs and devices are
safe and effective for women