1. S. HUNT Tenth International Symposium HEART FAILURE & Co. CARDIOLOGY SCIENCE UPDATE FEMALE DOCTORS SPEAKING ON FEMALE DISEASES Milano 9 - 10 aprile 2010

2. Tenth International Symposium HEART FAILURE & Co. Milano 9-10 Abrille 2010 Epidemiology of Heart Failure: The Need for Sex Specific Data Sharon A. Hunt, MD Stanford University, California

3. INTRODUCTION There is actually some good data on gender specific epidemiology in heart failure* *See (among others): Rosamond et al Heart disease and stroke statistics—2008 update: a report from the AHA statistics committee and stroke statistics subcommittee. Circ 2008;117:e25-146.

4. HEART FAILURE ITSELF APPEARS TO HAVE DIFFERENT EPIDEMIOLOGIC CHARACTERISTICS IN MEN AND WOMEN, ATTRIBUTABLE TO… Age. Age. Women older at onset Ventricular function. Ventricular function. Systolic more often preserved in women Systolic more often preserved in women Cause of HF. Cause of HF. Less often ischemic in women. Survival Survival Overall better for women Overall better for women

5. Copyright ©2008 American Heart Association Rosamond, W. et al. Circulation 2008;117:e25-e146 Prevalence of HF by sex and age 1999-2004

6. HEART FAILURE ITSELF APPEARS TO HAVE DIFFERENT EPIDEMIOLOGIC CHARACTERISTICS IN MEN AND WOMEN, ATTRIBUTABLE TO… Age. Age. Women older at onset Ventricular function. Ventricular function. Systolic more often preserved in women Systolic more often preserved in women Cause of HF. Cause of HF. Less often ischemic in women. Survival Survival Overall better for women Overall better for women

7. Hsich, E. M. et al. J Am Coll Cardiol 2009;54:491-498 Framingham Database – People with HF

8. Better LVEF, more CHF  Despite having a more preserved LV ejection fraction than men, women have higher rates of heart failure, likely reflecting differences in LV modeling and incidence of diastolic heart failure in women

9. HEART FAILURE ITSELF APPEARS TO HAVE DIFFERENT EPIDEMIOLOGIC CHARACTERISTICS IN MEN AND WOMEN, ATTRIBUTABLE TO… Age. Age. Women older at onset Ventricular function. Ventricular function. Systolic more often preserved in women Systolic more often preserved in women Cause of HF. Cause of HF. Less often ischemic in women. Survival Survival Overall better for women Overall better for women

10. Women less often have ischemic etiology of HF Pooled populations of 5 large clinical HF trials which included 8,791 men and 2,851 women showed: ISCHEMIC NON-ISCHEMIC MALE 57% 43% FEMALE 40% 60%

11. HEART FAILURE ITSELF APPEARS TO HAVE DIFFERENT EPIDEMIOLOGIC CHARACTERISTICS IN MEN AND WOMEN, ATTRIBUTABLE TO… Age. Age. Women older at onset Ventricular function. Ventricular function. Systolic more often preserved in women Systolic more often preserved in women Cause of HF. Cause of HF. Less often ischemic in women. Survival Survival Overall better for women Overall better for women

12. Hsich, E. M. et al. J Am Coll Cardiol 2009;54:491-498 Kaplan-Meier Curves for All-Cause Mortality in the CHARM Study

13. Frazier, C. G. et al. J Am Coll Cardiol 2007;49:1450-1458 Kaplan-Meier Probabilities of Survival by Etiology of Heart Failure and Gender POOLED DATA FROM 5 LARGE HF TRIALS

14. Overall, however, HF is getting more prevalent and costing more REASONS INCLUDE Increasing survival post-MI Increasing survival post-MI Better therapy prolonging lives Better therapy prolonging lives “Ageing” of the population “Ageing” of the population

15. Copyright ©2008 American Heart Association Rosamond, W. et al. Circulation 2008;117:e25-e146 Incidence of heart failue 1980-2003

16. Copyright ©2008 American Heart Association Rosamond, W. et al. Circulation 2008;117:e25-e146 Hospital discharges for HF by sex 1979-2005

17. Cost is Astronomical Estimated direct and indirect cost of HF in the US alone for the year 2008 $34.8 BILLION

18. Despite these striking epidemiological differences in HF between the sexes… Most clinical trials have not planned to prospectively analyze the female cohort or enroll any certain percentage of women.

19. Enrollment of Women in NHLBI RCTs Kim et al. J Am Coll Cardiol 2008;52:672-675 Mean percent of women enrolled in all trials (27%) vs. mean percent of all patients with CVD who were women (53%)

20. Some data have been teased out with meta-analyses: ACE INHIBITORS Probably work as well in women as in men, at least for treatment Probably work as well in women as in men, at least for treatment Possibly not for prevention of HF Possibly not for prevention of HF

21. Copyright ©2003 American College of Cardiology Foundation. Restrictions may apply. Shekelle, P. G. et al. J Am Coll Cardiol 2003;41:1529-1538 Effect of angiotensin-converting enzyme inhibitors on mortality in male and female patients with heart failure (random effects pooled estimate) MALE FEMALE

22. Some data have been teased out with meta-analyses: BETA BLOCKERS Similar meta-analysis strongly suggests similar reduced mortality when men and women with symptomatic HF treated with beta blockers There are, of course, no prevention Trials with beta blockers

23. Some data have been teased out with post-hoc analyses: ALDOSTERONE ANTAGONISTS Both RALES and EPHESUS show a total mortality benefit for women with systolic HF HYDRALAZINE/NITRATES A-HeFT was stopped prematurely for benefit in both men and women

24. Some data have been teased out with post-hoc analyses: DEVICE THERAPY CRT and ICD’S CRT and ICD’S Few of the large multicenter trials have reported sex-specific data Post-hoc analyses of the few women enrolled suggest that they do benefit