Journal Wrap | Women are typically underrepresented in individual cardiac resynchronization therapy (CRT) clinical trials—making up only 20% of enrollees. To better understand how CRT benefits men and women with left branch bundle block (LBBB) differently, Zusterzeel et al. pooled individual patient data from three large CRT-defibrillator (CRT-D) versus implantable cardioverter-defibrillator (ICD) trials enrolling predominantly patients with mild heart failure (HF; New York Heart Association class II) to test the hypothesis that in patients with LBBB, women benefit more than men from CRT-D at a shorter QRS duration.

Of the 4,076 patients included in this pooled analysis, 3,198 (78%) were men and 878 (22%) were women. Women were more likely than men to have LBBB (85% vs. 68%), but less likely to have ischemic cardiomyopathy (33% vs. 67%).

In women, CRT-D resulted in a 60% relative reduction in HF or death (CRT-D to ICD HR = 0.40; absolute difference of 15%), and a 55% relative reduction in death alone (absolute difference of 6%). Men, however, experienced relative reductions of only 26% and 15% (absolute differences, 7% and 2%) in the two endpoints, respectively.

Neither group of patients benefited from CRT-D at QRS shorter than 130 milliseconds, while both sexes with LBBB benefited at QRS of 150 milliseconds or longer. When patients were given CRT-D at QRS durations between 130 and 149 milliseconds, the difference between male and female patients' responses became greater: women had a 76% reduction in HF or death (absolute CRT-D to ICD difference = 23%; HR = 0.24 [95% CI 0.11-0.53]; p < 0.001) and a 76% reduction in death alone (absolute difference 9%; HR = 0.24, [95% CI, 0.06-0.89]; p = 0.03). There was no significant benefit in men for either HF or death or death alone (absolute differences = 4% and 2%, respectively).

Notably, these findings are true for both the endpoints of HF or death and death alone. "This is important because recent professional society guidelines for CRT-D only assign a class I indication to patients with LBBB and QRS of 150 milliseconds or longer," the authors wrote. However, these indications are based on trials in which approximately 80% of enrollees were men. For patients with LBBB and QRS of 120-149 milliseconds, CRT-D gets only a class IIa thumbs up from the guidelines, added to the fact women receive CRT-D less often than men.

So, what explains this relationship? This is not exactly a simple question: heart disease presents differently in men and women, and the results in the current study seem to support the use of sex-specific criteria for prescribing CRT-D. "The effectiveness and safety of medical products such as drugs, devices, and biologics can differ between women and men due to differences in prevalence of disease, physiology, body size, and a plethora of other intrinsic and extrinsic factors," they added.

In order to ensure that devices are available to both sexes, it is important that both sexes are represented consistently with disease prevalence. "An individual-patient data meta-analysis such as this one is a summary of safety and effectiveness data and is a logical mechanism for reporting safety and effectiveness inpatient subgroups that are underrepresented in individual trials."

Zusterzeel R, Selzman KA, Sanders WE, et al. JAMA Intern Med. 2014 June 23. [Epub ahead of print]

Keywords: CardioSource WorldNews Interventions

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