title: Persistent use of evidence-based pharmacotherapy in heart failure is associated with improved outcomes.
abstract: BACKGROUND
  Undertreatment with recommended pharmacotherapy is a common problem in heart failure and may influence prognosis. We studied initiation and persistence of evidence-based pharmacotherapy in 107,092 patients discharged after first hospitalization for heart failure in Denmark from 1995 to 2004.
  
  
  RESULTS
  Prescriptions of dispensed medication and mortality were identified by an individual-level linkage of nationwide registers. Inclusion was irrespective of left ventricular function. Treatment with renin-angiotensin inhibitors (eg, angiotensin-converting enzyme inhibitors and angiotensin-2 receptor blockers), beta-blockers, spironolactone, and statins was initiated in 43%, 27%, 19%, and 19% of patients, respectively. Patients who did not initiate treatment within 90 days of discharge had a low probability of later treatment initiation. Treatment dosages were in general only 50% of target dosages and were not increased during long-term treatment. Short breaks in therapy were common, but most patients reinitiated treatment. Five years after initiation of treatment, 79% patients were still on renin-angiotensin inhibitors, 65% on beta-blockers, 56% on spironolactone, and 83% on statins. Notably, multiple drug treatment and increased severity of heart failure was associated with persistence of treatment. Nonpersistence with renin-angiotensin inhibitors, beta-blockers, and statins was associated with increased mortality with hazard ratios for death of 1.37 (95% CI, 1.31 to 1.42), 1.25 (95% CI, 1.19 to 1.32), 1.88 (95% CI, 1.67 to 2.12), respectively.
  
  
  CONCLUSIONS
  Persistence of treatment was high once medication was started, but treatment dosages were below recommended dosages. Increased severity of heart failure or increased number of concomitant medications did not worsen persistence, but nonpersistence identified a high-risk population of patients who required special attention. A focused effort on early treatment initiation, appropriate dosages, and persistence with the regimen is likely to provide long-term benefit.
authors.affiliation: Department of Cardiology, Gentofte University Hospital, Hellerup, Denmark. gg@heart.dk
authors.forename: Gunnar H
authors.initials: GH
authors.lastname: Gislason
authors.forename: Jeppe N
authors.initials: JN
authors.lastname: Rasmussen
authors.forename: Steen Z
authors.initials: SZ
authors.lastname: Abildstrom
authors.forename: Tina Ken
authors.initials: TK
authors.lastname: Schramm
authors.forename: Morten Lock
authors.initials: ML
authors.lastname: Hansen
authors.forename: Pernille
authors.initials: P
authors.lastname: Buch
authors.forename: Rikke
authors.initials: R
authors.lastname: Sørensen
authors.forename: Fredrik
authors.initials: F
authors.lastname: Folke
authors.forename: Niels
authors.initials: N
authors.lastname: Gadsbøll
authors.forename: Søren
authors.initials: S
authors.lastname: Rasmussen
authors.forename: Lars
authors.initials: L
authors.lastname: Køber
authors.forename: Mette
authors.initials: M
authors.lastname: Madsen
authors.forename: Christian
authors.initials: C
authors.lastname: Torp-Pedersen
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000627:therapeutic use; D000328:Adult; D057912:Angiotensin II Type 2 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D002303:Cardiac Output, Low / Q000188:drug therapy* / Q000401:mortality; D003718:Denmark; D011307:Drug Prescriptions / Q000706:statistics & numerical data; D019317:Evidence-Based Medicine; D017052:Hospital Mortality; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D010349:Patient Compliance; D013148:Spironolactone / Q000008:administration & dosage / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D057912:Angiotensin II Type 2 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D013148:Spironolactone