title: The implications of therapeutic complexity on adherence to cardiovascular medications.
abstract: BACKGROUND
  Patients with chronic disease often take many medications multiple times per day. Such regimen complexity is associated with medication nonadherence. Other factors, including the number of pharmacy visits patients make to pick up their prescriptions, may also undermine adherence. Our objective was to estimate the extent of prescribing and filling complexity in patients prescribed a cardiovascular medication and to evaluate its association with adherence.
  
  
  METHODS
  The study population comprised individuals prescribed a statin (n = 1 827 395) or an angiotensin- converting enzyme inhibitor or renin angiotensin receptor blocker (ACEI/ARB) (n = 1 480 304) between June 1, 2006, and May 30, 2007. We estimated complexity by measuring the number of medications, prescribers, pharmacies, pharmacy visits, and refill consolidation (a measure of the number of visits per fill) during the 3 months from the first prescription. The number of daily doses was also measured in ACEI/ARB users. After this period, adherence was evaluated over the subsequent year. The relationship between complexity and adherence was assessed with multivariable linear regression.
  
  
  RESULTS
  The statin cohort had a mean age of 63 years and were 49% male. On average, during the 3-month complexity assessment period, statin users filled 11.4 prescriptions for 6.3 different medications, had prescriptions written by 2 prescribers, and made 5.0 visits to the pharmacy. Results for ACEI/ARB users were similar. Greater prescribing and filling complexity was associated with lower levels of adherence. In adjusted models, patients with the least refill consolidation had adherence rates that were 8% lower over the subsequent year than patients with the greatest refill consolidation.
  
  
  CONCLUSIONS
  Medication use and prescription filling for patients with cardiovascular disease is complex, and strategies to reduce this complexity may help improve medication adherence.
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02120, USA. nchoudhry@partners.org
authors.forename: Niteesh K
authors.initials: NK
authors.lastname: Choudhry
authors.forename: Michael A
authors.initials: MA
authors.lastname: Fischer
authors.forename: Jerry
authors.initials: J
authors.lastname: Avorn
authors.forename: Joshua N
authors.initials: JN
authors.lastname: Liberman
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schneeweiss
authors.forename: Juliana
authors.initials: J
authors.lastname: Pakes
authors.forename: Troyen A
authors.initials: TA
authors.lastname: Brennan
authors.forename: William H
authors.initials: WH
authors.lastname: Shrank
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000008:administration & dosage; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D002317:Cardiovascular Agents / Q000008:administration & dosage*; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D002908:Chronic Disease; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D019338:Polypharmacy; D010818:Practice Patterns, Physicians'
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D002317:Cardiovascular Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors