Tenth International Symposium
HEART FAILURE & Co.
CARDIOLOGY SCIENCE UPDATE
FEMALE DOCTORS SPEAKING
ON FEMALE DISEASES
Milano
9 - 10 aprile 2010
ICD data in Women are Inconclusive:
Do we need a sex specific trial?
Valeria Calvi
Università di Catania
U.O. di Aritmologia Ospedale Ferrarotto
Cattedra di Cardiologia
Università di Catania
ICD Trials
Cattedra di Cardiologia
Università di Catania
2004
Cattedra di Cardiologia
Università di Catania
Survival Free From Overall
Arrhythmic
Death or Cardiac Arrest
Survival
2004
Cattedra di Cardiologia
Università di Catania
■ 1232 patients: 192 (16%) women and 1,040 (84%) men
■ The cumulative probability of sudden cardiac death in
conventionally treated patients was similar by gender
■ In the ICD treatment arm, the 2-year mortality rate was
found to be 16% in both men and women
2005
Cattedra di Cardiologia
Università di Catania
■ 2-year probability of appropriate ICD therapy for
VT/VF was significantly lower in women
■ Cumulative probability of death after first
appropriate ICD therapy was non significantly
different
■ Women presented with somewhath higher risk of
hospitalization for CHF in both treatment groups
2005
Cattedra di Cardiologia
Università di Catania
■ 458 patients: 326 man (71%), 132 women (29%)
■ No difference in the incidence of arrhythmic death in
men (n = 10; 6%) versus women (n = 4; 6%)
■ No evidence for a sex difference in the effectiveness
of the ICD in reducing mortality among patients with
NISCM
2008
Cattedra di Cardiologia
Università di Catania
■ A total of 2,521 patients, 588 (23%) women and
1,933 (77%) men
■ Treatment effects appear different between
genders with a smaller ICD benefit among women;
but this difference was not significant (P=0,54)
2008
Cattedra di Cardiologia
Università di Catania
■ No difference in risk of cardiac arrhythmic death in
men versus women (36% vs. 39%, P = 0.34)
■ No difference in the risk of appropriate shock
therapy for men versus women (P = 0.25).
2008
Cattedra di Cardiologia
Università di Catania
2008
Cattedra di Cardiologia
Università di Catania
■1.530 patients, women comprised 19%
(293/1.530)
■After adjusting for baseline characteristics
and medical therapy, there was no
significant difference in the outcome and
mortality between women and men (HR =
1.05, P = 0.83)
2009
Cattedra di Cardiologia
Università di Catania
■ A total of 6% of men and 8% of women received an
■
appropriate ICD shock during the follow-up (HR = 1.37, P =
0.19)
Adverse events (pulse generator-, lead-, and patient-related
cardiovascular events) were observed more commonly in
women
2009
Cattedra di Cardiologia
Università di Catania
Mortality
Mortalityamong
amongwomen
men with
withsystolic
systolicdysfunction
dysfunctionrandomized
randomizedtotoICD
ICD
implantation vs medical therapy for the primary prevention of SCD
Cattedra di Cardiologia
Università di Catania
Cattedra di Cardiologia
Università di Catania
Benefits of ICD in women
No trial powered to separately examine outcomes in men
and women or test for difference in ICD effectiveness
Small numbers of women enrolled
Limited post-hoc analyses for females do not clearly
demonstrate a mortality benefit:
-
SCD-HeFT: benefit not clear (not powered for gender)
MADIT II: nonsignificant trend to lower mortality in females
but analysis limited by too few female subjects
Meta-analysis: 934 females in 5 trials; no difference in allcause mortality for women with ICD vs medical Rx
Cattedra di Cardiologia
Università di Catania
Am Heart J 1998
Cattedra di Cardiologia
Università di Catania
JACC 2009
 The prevalence of HF increases with age for both
sexes, with more women than men having HF after
79 years of age
 Survival is better for women
- Women with acute decompensated HF tend to have
preserved LV function almost twice as often as men and
those with impaired LV systolic function tend to present
with a higher LVEF when compared with men
- Women have less ischemic cardiomyopathy
- Other?
Gender differences in geometric remodeling, myocyte cell
loss, and gene expression have been reported
Cattedra di Cardiologia
Università di Catania
SCD in Women
CAD is the most common
urderlying cardiovascular
disease in patients with SCD
JACC 2009
Cattedra di Cardiologia
Università di Catania
Demographics and Cardiac Arrest Circumstances
in Men and Women Age >35 Years With SCA
(n 1,568)
Portland, Oregon, Metropolitan Area, Feb 2002 to Jan 2007
Cattedra di Cardiologia
Università di Catania
Conclusions
Since fewer women may be eligible for ICD
implantation based on LVEF criteria alone, the
identification of novel SCA risk predictors for
women becomes an important priority.
JACC 2009
Cattedra di Cardiologia
Università di Catania
ICD in Women
Men are significantly more likely to undergo
ICD implantion for both primary and
■ Community-based
studies reported
secondary prevention
of SCAthat
only 25% to 30% of SCAs occur in subjects
who have severely reduced LV systolic
function
■ Women account for only 10%-29% of the
study populations in ICD clinical trials
Cattedra di Cardiologia
Università di Catania
■Women represent 27% of patients receiving ICD for primary
prevention in clinical practice in USA.
■Possible explanations:
- Selection criteria are applied more stringently to women
- Trial criteria are being applied more stringently among
older women than older men with no significant gender
differences among younger patients
- Women are less commonly referred for invasive cardiac
procedures
- Older women have more coexisting illnesses and higher
complication rates and are therefore viewed as less likely
to benefit from therapy
- Older women may be more likely to refuse ICD therapy
compared to men
- Higher complications rates of ICD implantation in women
Am Heart J 2009
Cattedra di Cardiologia
Università di Catania
2009
161.470 pts, 27% women
Cattedra di Cardiologia
Università di Catania
Conclusions
■ Females with lower rates of SCD than
males
■ Differences in arrhythmia susceptibility
■ 30% of ICDs are implanted in females
■ Even though the benefit is less, it may
represent a clinically significant reduction
in deaths
Ghanbari et al. Arch Int Med 2009
Redberg RF. Arch Int Med 2009
Cattedra di Cardiologia
Università di Catania
Conclusions
A trial targeting women is needed
 To detect the same ICD benefit in women
as was observed in men with 90% power
and α=0.05, a study larger than SCDHeFT
would be required (1.585 women in each
treatment arm, 3.170 total)
 It may now even be considered “unethical”
to withhold ICD therapy in women meeting
the SCD-HeFT enrollment criteria.
Cattedra di Cardiologia
Università di Catania
L’ingiustizia di
sempre…