Cardiac Resynchronization Therapy With Defibrillators May Reduce Mortality in Women

Implantable cardioverter-defibrillators (ICDs) are equally effective at reducing all-cause and cardiac mortality in men and women, and cardiac resynchronization therapy with defibrillators (CRT-D) may lower all-cause and cardiac mortality in women more than in men according to a study in Heart Rhythm.

Researchers evaluated sex-based differences regarding the mode of death and device efficacy of ICD and CRT-D in the MADIT-II, MADIT-CRT, and MADIT-RIT trials.

The overall population included 3038 men and 1000 women with ischemic cardiomyopathy (ICM) or nonischemic cardiomyopathy (NICM) who received an ICD or CRT-D. The women with ICM (n=375) had a mean age at death of 66.9±9.6 years vs 71.0±8.7 years for men with ICM (n=2135). The women with NICM (n=625) had a mean age at death of 69.2±14.1 years vs 61.0±14.2 years for men with NICM (n=903).


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The most frequent type of death in men was nonarrhythmic cardiac death (41%), followed by noncardiac death (34%) and arrhythmic cardiac death (17%). For women, noncardiac death was most common (33%), followed by nonarrhythmic cardiac death (29%) and arrhythmic cardiac death (20%).

A total of 295 men and 66 women died (9.7% vs 6.6%; P =.003) during a median follow-up of 26 months. Men had a significantly higher cumulative probability of all-cause death compared with women, with an annual mortality rate of 4% per year for men and 2.5% per year for women (P =.004).

Men had a nonsignificant difference in all-cause mortality compared with women for ischemic heart disease (5% vs 3.3% per year; P =.222), and no difference occurred for nonischemic heart disease (2.3% vs 2.3% per year; P =.889).

The mortality risk for men was substantially increased (41%) but not statistically significant compared with women with ischemic heart disease (hazard ratio [HR], 1.41; 95% CI, 0.98-2.04; P =.063) after controlling for relevant clinical covariates. A similar risk was observed between men and women with nonischemic heart disease (HR, 1.05; P =.524) according to Cox proportional hazards regression analysis.

A trend toward an approximate 2-fold increase was observed in the risk of nonarrhythmic cardiac death in men vs women with ischemic heart disease (HR, 1.88; P =.057), and no difference was found in those with nonischemic disease, per Cox proportional regression analysis.

Noncardiac death was 2-fold higher in men and women with ICM compared with patients with NICM. After adjustment, no difference was found in noncardiac death by sex with ischemic (HR, 1.20; P =.538) or nonischemic heart disease (HR, 1.30; P =.524).

All-cause mortality was increased significantly in men who qualified for but did not receive an ICD (19.4%-27.2%) vs men who received an ICD (10.3%) or CRT-D (9.1%). Women had a similarly lower rate of all-cause mortality for those who received an ICD (10%) or CRT-D (3.9%) vs historical cohorts (21.9%-22.6%). The lower rate of all-cause mortality was mainly accounted for by a lower rate of arrhythmic and nonarrhythmic cardiac death in men and women with an ICD or CRT-D vs patients without a defibrillator.

Some study limitations are that cohorts from 3 trials are used in the analysis, and enrollment criteria are not identical and could introduce selection bias. Also, the 3 trials were conducted over 14 years, and this study does not include recent advances in medical therapies.

“Our findings provide important clinical implications when assessing mortality risk in male and female patients with an implanted ICD or CRT-D,” the investigators wrote. “Women are generally thought to be at a lower risk of all-cause mortality and nonarrhythmic cardiac death than men, but our data suggest that this may not be the case in those with nonischemic cardiomyopathy.”

Disclosure: The original MADIT studies were supported by research grants from Boston Scientific. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Tompkins CM, Zareba W, Greenberg H, et al. Differences in mode of death between men and women receiving implantable cardioverter defibrillators or cardiac resynchronization therapy in the MADIT trials. Heart Rhythm. Published online August 21, 2022. doi: 10.1016/j.hrthm.2022.08.018

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