Cardiac Resynchronization Therapy in Women: US Food and Drug Administration Meta-Analysis of Patient-Level Data
Do women with left bundle branch block (LBBB) benefit from cardiac resynchronization therapy-defibrillators (CRT-Ds) at a shorter QRS duration than men with LBBB do?
Individual patient data were pooled from three CRT-D versus implantable cardioverter-defibrillator (ICD) trials (4,076 patients) enrolling predominantly patients with New York Heart Association (NYHA) class II heart failure and follow-up to 3 years. The effect of CRT-D compared with ICD on outcomes was assessed using random-effects Cox proportional hazards.
Women benefited from CRT-D more than men. The main difference occurred in patients with LBBB and a QRS of 130-149 ms. In this group, women had a 76% reduction in heart failure or death (absolute CRT-D to ICD difference, 23%; hazard ratio [HR], 0.24; 95% confidence interval [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), while there was no significant benefit in men for heart failure or death (absolute difference, 4%; HR, 0.85; 95% CI, 0.60-1.21; p = 0.38) or death alone (absolute difference, 2%; HR, 0.86; 95% CI, 0.49-1.52; p = 0.60). Neither women nor men with LBBB benefited from CRT-D at a QRS shorter than 130 ms, whereas both sexes with LBBB benefited at a QRS of 150 ms or longer.
In this population of patients with primarily mild heart failure, women with LBBB benefited from CRT-D at a shorter QRS duration than men with LBBB. This is important because recent guidelines limit the Class I indication for CRT-D to patients with LBBB and QRS of 150 ms or longer. While guidelines do give a Class IIa indication to patients with LBBB and a QRS of 120-149 ms, the present findings are important to communicate because women are less likely to receive a CRT-D than men. This study exemplifies the potential public health and regulatory science value of combining data from multiple clinical trials submitted to the Food and Drug Administration.
The current study lends support to the use of sex-specific criteria for LBBB. It has been suggested that men have a higher incidence of left ventricular hypertrophy with left anterior fascicular block masquerading as LBBB. Furthermore, because of potential sex-specific differences in outcomes, this study highlights the need for greater representation of women in clinical studies.
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