Cardiac resynchronization therapy in women: US Food and Drug Administration meta-analysis of patient-level data

Abstract

Importance: Women were underrepresented in cardiac resynchronization therapy (CRT) trials for heart failure (making up about 20% of enrollees). Combining individual patient data from multiple clinical trials would enable assessment of CRT benefit in women.

Objective: To evaluate whether women with left bundle branch block (LBBB) benefit from CRT-defibrillators (CRT-D) at a shorter QRS duration than men with LBBB do.

Design, setting, and participants: Individual patient data were pooled from 3 CRT-D vs implantable cardioverter defibrillator (ICD) trials (4076 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.

Main outcomes and measures: Time to heart failure event or death (primary) and death alone (secondary).

Results: Women benefited from CRT-D more than men. The main difference occurred in patients with LBBB and a QRS of 130 to 149 milliseconds. 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% CI, 0.11-0.53]; P < .001) and a 76% reduction in death alone (absolute difference 9%; HR, 0.24, [95% CI, 0.06-0.89]; P = .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 = .38) or death alone (absolute difference 2%; HR, 0.86 [95% CI, 0.49-1.52]; P = .60). Neither women nor men with LBBB benefited from CRT-D at QRS shorter than 130 milliseconds, while both sexes with LBBB benefited at QRS of 150 milliseconds or longer.

Conclusions and relevance: 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 milliseconds or longer. While guidelines do give a class IIa indication to patients with LBBB and a QRS of 120 to 149 milliseconds, the present findings are important to communicate because women are less likely to receive CRT-D than men are. This study exemplifies the potential public health and regulatory science value of combining data from multiple clinical trials submitted to the FDA.