title: Treatment Initiation Patterns, Modifications, and Medication Adherence Among Newly Diagnosed Heart Failure Patients: A Retrospective Claims Database Analysis.
abstract: BACKGROUND
  Heart failure (HF) is a debilitating disease associated with high mortality and frequent hospitalizations. American College of Cardiology Foundation and American Heart Association (ACCF/AHA) guidelines recommend the following drug classes for HF treatment: angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor II blocker (ARB) for patients intolerant to ACEI, beta blocker (BB), and aldosterone antagonist (AA).
  
  
  OBJECTIVE
  To examine, in a real-word setting, the treatment initiation pattern among newly diagnosed HF patients in the United States, subsequent treatment modifications, hospitalizations and the impact of hospitalizations on therapy changes, and treatment adherence and persistence.
  
  
  METHODS
  Using medical and pharmacy claims data from the Truven Health MarketScan database, this retrospective cohort study included adult patients with ≥ 2 medical claims corresponding to an HF diagnosis (ICD-9-CM codes 428.x, 402.11, 402.91, 404.01, 404.11, 404.91, 404.03, 404.13, and 404.93) between April 2009 and March 2012. The date of the first claim was defined as the index date. Patients with continuous medical and pharmacy eligibility for a minimum of 12 months pre- and post-index were included in the analysis. Patients with an HF diagnosis in the 12 months before the index date were excluded. Index treatment (within 30 days post-index), subsequent treatment modification (class addition/removal) during the study period, hospitalization, and change in treatment after hospitalization (within 15 days after hospital discharge) were determined. Adherence was evaluated using the proportion of days covered (PDC) method, and persistence was defined as the proportion of patients remaining on index treatment after a defined period of time (12 months).
  
  
  RESULTS
  A total of 235,758 patients meeting the sample selection criteria were included in the analysis and were followed for a median of 28 months after the index date. Approximately 42% of patients were not prescribed any HF-specific treatment within 30 days post-index. Among those treated, prescriptions for ACEIs were filled by 46.42% of patients, ARBs by 17.07%, BBs by 75.62%, and AAs by 9.83%. Based on HF therapy class, monotherapy was prescribed to 51% of patients, bi-therapy to 40%, and triple therapy to 9%. More than 80% of patients experienced treatment modification during the median 28 months of follow-up. A total of 174,563 (74.0%) patients had at least 1 all-cause hospitalization (mean 1.11 [SD = 0.98]) per year, with a mean length of stay (LOS) of 7.19 [SD = 8.69] days. Within 12 months post-index, 85.7% of these patients experienced an all-cause hospitalization, with 29.6% having HF-related hospitalization (mean 0.18 [0.36]) and mean LOS of 5.85 [5.45] days. More than 60% of patients continued on the same therapy after all-cause or HF hospitalization. More patients on multiple therapies remained on the same treatment (73%-89%) compared with those treated with monotherapy (60%-73%) after the first HF hospitalization. Among patients untreated before hospitalization, 9.8% and 17% received treatment after all-cause and HF hospitalization, respectively. During the entire study period (median 28 months), 29% of patients did not have a prescription fill for HF-specific treatments. The median PDC was > 0.65, and considering a gap of 30 days between ends of supply from 1 medication fill to the subsequent fill, persistence ranged from 41% (AA) to 52% (BB).
  
  
  CONCLUSIONS
  Findings of this claims database analysis among 235,758 HF patients suggest that more than one third of newly diagnosed HF patients do not receive HF-specific medication within 30 days following initial diagnosis. Despite ACCF/AHA recommendations of initiating treatment with a combination of 2 HF drug classes, only 40% of patients had a prescription fill for bi-therapy. Hospitalization did not have a major impact on HF therapy prescribing patterns. To our knowledge, this is the first study to establish the impact of hospitalization on HF-specific treatment among newly diagnosed patients. Adherence and persistence were moderate across all HF therapies of interest. This analysis reveals the need for further research to better understand the reasons for the demonstrated delay in HF treatment initiation and limited use of guideline-directed medical therapy after initial diagnosis.
  
  
  BACKGROUND
  This study was funded by Novartis Pharma AG, Basel, Switzerland. Deschaseaux, McSharry, Hudson, Agrawal, and Turner are permanent employees of Novartis. Concept and study design were contributed by Deschaseaux, Hudson, and Turner, along with McSharry. McSharry took the lead in data collection, along with Deschaseaux, Hudson, and Turner. Data interpretation was performed by Hudson, along with the other authors. The manuscript was written by Agrawal, along with Deschaseaux and Turner, and revised by Deschaseaux and Turner, along with the other authors.
authors.affiliation: 1 Novartis Pharma AG, Basel, Switzerland.
authors.forename: Céline
authors.initials: C
authors.lastname: Deschaseaux
authors.affiliation: 2 Novartis Ireland Ltd, Dublin, Ireland.
authors.forename: Martin
authors.initials: M
authors.lastname: McSharry
authors.affiliation: 2 Novartis Ireland Ltd, Dublin, Ireland.
authors.forename: Eibhlin
authors.initials: E
authors.lastname: Hudson
authors.affiliation: 3 Novartis Healthcare Private Limited, Hyderabad, India.
authors.forename: Rumjhum
authors.initials: R
authors.lastname: Agrawal
authors.affiliation: 4 Novartis Pharmaceuticals, East Hanover, New Jersey, United States.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Turner
mesh_terms: D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D016208:Databases, Factual; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006760:Hospitalization; D006801:Humans; D038801:International Classification of Diseases; D008297:Male; D008329:Managed Care Programs; D008875:Middle Aged; D012189:Retrospective Studies; D014481:United States; D055815:Young Adult; D016903:Drug Monitoring
chemical_list: D000319:Adrenergic beta-Antagonists; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents