title: Prognosis and response to therapy of first inpatient and outpatient heart failure event in a heart failure clinical trial: MADIT-CRT.
abstract: OBJECTIVE
  Hospitalization for worsening heart failure (HF) is known to increase mortality and morbidity risk and has been frequently used as an endpoint in randomized clinical trials. Whether outpatient management of HF exacerbation carries similar prognostic and therapeutic information is less well known, but could be important for the design of trials that use HF hospitalization as an endpoint.
  
  
  RESULTS
  MADIT-CRT randomized patients with mild HF symptoms to resynchronization therapy vs. control with an average follow-up of 3.3 years and a total of 191 deaths. HF events were centrally adjudicated for receiving i.v. decongestive therapy in an outpatient setting, or an augmented HF regimen during a hospital stay. Patients were compared according to whether their first HF was an out- or inpatient event. The first primary event was non-fatal outpatient HF, non-fatal inpatient HF, and death in 52, 331, and 78 patients, respectively. Patients with inpatient HF tended to be older and more likely to have HF of ischaemic aetiology than subjects who developed outpatient HF events. The risk of death following either type of non-fatal HF events was extremely high [hazard ratio (HR) 12.4, 95% confidence interval (CI) 9.1-16.9 for inpatient HF; HR 10.7, 95% CI 6.1-18.7 for outpatient HF] compared with subjects without non-fatal HF events. Allocation to CRT-D was associated with significant reduction in both types of HF.
  
  
  CONCLUSIONS
  Outpatient management of worsening HF portends a high risk of death, similar to inpatient HF events, and may be equally sensitive to the effects of therapy. These findings suggest that outpatient HF events should be considered in publicly reported outcomes measures and future HF clinical trials.
  
  
  BACKGROUND
  NCT01294449.
authors.affiliation: Harvard Medical School, Brigham and Women's Hospital, Cardiovascular Division, Boston, MA, USA.
authors.forename: Hicham
authors.initials: H
authors.lastname: Skali
authors.forename: Edward M
authors.initials: EM
authors.lastname: Dwyer
authors.forename: Robert
authors.initials: R
authors.lastname: Goldstein
authors.forename: Mark
authors.initials: M
authors.lastname: Haigney
authors.forename: Ronald
authors.initials: R
authors.lastname: Krone
authors.forename: Marrick
authors.initials: M
authors.lastname: Kukin
authors.forename: Edgar
authors.initials: E
authors.lastname: Lichstein
authors.forename: Scott
authors.initials: S
authors.lastname: McNitt
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Moss
authors.forename: Marc A
authors.initials: MA
authors.lastname: Pfeffer
authors.forename: Scott D
authors.initials: SD
authors.lastname: Solomon
mesh_terms: D000367:Age Factors; D000368:Aged; D058406:Cardiac Resynchronization Therapy / Q000379:methods*; D017147:Defibrillators, Implantable; D018450:Disease Progression; D005260:Female; D006333:Heart Failure / Q000175:diagnosis / Q000209:etiology / Q000401:mortality / Q000503:physiopathology / Q000628:therapy; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007297:Inpatients / Q000706:statistics & numerical data*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000150:complications; D010045:Outpatients / Q000706:statistics & numerical data*; D011379:Prognosis; D012307:Risk Factors; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014481:United States
keywords: Clinical trials; Endpoint; Heart failure; Outpatient