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

Tenth International Symposium

HEART FAILURE & Co.CARDIOLOGY SCIENCE UPDATE FEMALE DOCTORS SPEAKING

ON FEMALE DISEASES

Milano9 - 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 CardiologiaUniversità di Catania

ICD Trials


2004


Survival Free From Arrhythmic Death or Cardiac ArrestOverall Survival

2004


■ 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


2005

■ 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


■ 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


■ 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


■ 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


2008


■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


■ 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


Mortality among men with systolic dysfunction randomized to ICD implantation vs medical therapy for the primary prevention of SCD

Mortality among women with systolic dysfunction randomized to ICD implantation vs medical therapy for the primary prevention of SCD



Benefits of ICD in womenNo 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 all-cause mortality for women with ICD vs medical Rx


Am Heart J 1998


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

JACC 2009


SCD in Women

JACC 2009

CAD is the most common urderlying cardiovascular disease in patients with SCD


Portland, Oregon, Metropolitan Area, Feb 2002 to Jan 2007(n 1,568)

Demographics and Cardiac Arrest Circumstancesin Men and Women Age >35 Years With SCA


ConclusionsSince 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


ICD in Women

■ Community-based studies reported that 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

Men are significantly more likely to undergo ICD implantion for both primary and

secondary prevention of SCA


■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 womenAm Heart J 2009


2009

161.470 pts, 27% women


■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

Conclusions


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.


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