title: Days alive and out of hospital and the patient journey in patients with heart failure: Insights from the candesartan in heart failure: assessment of reduction in mortality and morbidity (CHARM) program.
abstract: BACKGROUND
  Conventional composite outcomes in heart failure (HF) trials, for example, time to cardiovascular death or first HF hospitalization, have recognized limitations. We propose an alternative outcome, days alive and out of hospital (DAOH), which incorporates mortality and all hospitalizations into a single measure. A refinement, the patient journey, also uses functional status (New York Heart Association [NYHA] class) measured during follow-up. The CHARM program is used to illustrate the methodology.
  
  
  METHODS
  CHARM randomized 7,599 patients with symptomatic HF to placebo or candesartan, with median follow-up of 38 months. We related DAOH and percent DAOH (ie, percentage of time spent alive and out of hospital) to treatment using linear regression adjusting for follow-up time.
  
  
  RESULTS
  Mean increase in DAOH for patients on candesartan versus placebo was 24.1 days (95% CI 9.8-38.3 days, P < .001). The corresponding mean increase in percent DAOH was 2.0% (95% CI 0.8%-3.1%, P < .001). These findings were dominated by reduced mortality (23 days) but enhanced by reduced time in hospital (1 day). Percent time spent in hospital because of HF was reduced by 0.10% (95% CI 0.04%-0.14%, P < .001). The patient journey analysis showed that patients in the candesartan group spent more follow-up time in NYHA classes I and II and less in NYHA class IV.
  
  
  CONCLUSIONS
  Days alive and out of hospital, especially percent DAOH, provide a valuable tool for summarizing the overall absolute treatment effect on mortality and morbidity. In future HF trials, percent DAOH can provide a useful alternative perspective on the effects of treatment.
authors.affiliation: Department of Medical Statistics, London School of Hygiene and Tropical Medicine, United Kingdom. cono.ariti@lshtm.ac.uk
authors.forename: Cono A
authors.initials: CA
authors.lastname: Ariti
authors.forename: John G F
authors.initials: JG
authors.lastname: Cleland
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Pocock
authors.forename: Marc A
authors.initials: MA
authors.lastname: Pfeffer
authors.forename: Karl
authors.initials: K
authors.lastname: Swedberg
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Granger
authors.forename: John J V
authors.initials: JJ
authors.lastname: McMurray
authors.forename: Eric L
authors.initials: EL
authors.lastname: Michelson
authors.forename: Jan
authors.initials: J
authors.lastname: Ostergren
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
mesh_terms: D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage*; D001562:Benzimidazoles / Q000008:administration & dosage*; D001713:Biphenyl Compounds; D005260:Female; D006333:Heart Failure / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D016014:Linear Models; D008297:Male; D015233:Models, Statistical; D009026:Mortality; D016032:Randomized Controlled Trials as Topic; D012720:Severity of Illness Index; D013777:Tetrazoles / Q000008:administration & dosage*; D016896:Treatment Outcome; D014481:United States
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; C081643:candesartan