title: Cardiac resynchronization therapy in women: US Food and Drug Administration meta-analysis of patient-level data.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.
authors.affiliation: Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Robbert
authors.initials: R
authors.lastname: Zusterzeel
authors.affiliation: Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Selzman
authors.affiliation: Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, Maryland.
authors.forename: William E
authors.initials: WE
authors.lastname: Sanders
authors.affiliation: Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Caños
authors.affiliation: Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: O'Callaghan
authors.affiliation: Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Carpenter
authors.affiliation: Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Ileana L
authors.initials: IL
authors.lastname: Piña
authors.affiliation: Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, Maryland.
authors.forename: David G
authors.initials: DG
authors.lastname: Strauss
mesh_terms: D000368:Aged; D002037:Bundle-Branch Block / Q000401:mortality / Q000628:therapy*; D058406:Cardiac Resynchronization Therapy / Q000379:methods*; D058409:Cardiac Resynchronization Therapy Devices; D017147:Defibrillators, Implantable; D005260:Female; D006333:Heart Failure / Q000401:mortality / Q000628:therapy*; D006801:Humans; D008875:Middle Aged; D016016:Proportional Hazards Models; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration