• Robbert Zusterzeel, Kimberly A Selzman, William E Sanders, Daniel A Caños, Kathryn M O'Callaghan, Jamie L Carpenter, Ileana L Piña, and David G Strauss.
• Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, Maryland.
• JAMA Intern Med. 2014 Aug 1; 174 (8): 1340-8.

ImportanceWomen 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.ObjectiveTo 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 ParticipantsIndividual 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 MeasuresTime to heart failure event or death (primary) and death alone (secondary).ResultsWomen 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 RelevanceIn 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.

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