title: Effect of Combination Therapy on Adherence Among US Patients Initiating Therapy for Hypertension: a Cohort Study.
abstract: BACKGROUND
  New trial evidence suggests that many patients may require more aggressive pharmacologic management to achieve lower blood pressure goals. Especially when first initiating anti-hypertensive treatment, it is unknown whether starting patients on multiple medications may be better for long-term adherence and persistence compared with starting one medication.
  
  
  OBJECTIVE
  To examine contemporary patterns of anti-hypertensive therapy initiation and compare long-term adherence and persistence among patients initiating fixed-dose combinations and single anti-hypertensive therapies.
  
  
  METHODS
  Retrospective cohort study.
  
  
  METHODS
  Using claims from a large nationwide insurer, we identified all patients initiating oral hypertension treatment from 2009 to 2013. We categorized patients into three categories based on the number and type of anti-hypertensive medications they initiated: a fixed-dose combination, a multi-pill combination or a single therapy.
  
  
  METHODS
  The primary outcome was persistence to any anti-hypertensive medication, either the initiated medication or other anti-hypertensive, 12 months after initiation in administrative claims. We also measured adherence to at least one anti-hypertensive in the 12 months after initiation and refilling at least one anti-hypertensive medication as outcomes. Full adherence was defined as having ≥80% of potential days covered with medication. Multivariable modified Poisson regression models were used to examine the association between initiating a fixed-dose combination anti-hypertensive and medication outcomes.
  
  
  RESULTS
  Of the 484,493 patients who initiated oral anti-hypertensives, 78,958 patients initiated fixed-dose combinations, 383,269 initiated a single therapy, and 22,266 initiated multi-pill combinations. Patients initiating fixed-dose combinations were 9% more likely to be persistent (relative risk [RR]: 1.09, 95% CI: 1.08-1.10) and 13% more likely to be adherent (RR: 1.13 95% CI: 1.11-1.14) than those who started on a single anti-hypertensive therapy. Refill rates were also slightly higher among fixed-dose combination initiators.
  
  
  CONCLUSIONS
  Fixed-dose combination pills appear to enhance adherence and persistence to anti-hypertensive medications among commercially insured patients starting treatment compared with single therapy.
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 1620 Tremont Street, Suite 3030, Boston, MA, 02120, USA. jlauffenburger@bwh.harvard.edu.
authors.forename: Julie C
authors.initials: JC
authors.lastname: Lauffenburger
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 1620 Tremont Street, Suite 3030, Boston, MA, 02120, USA.
authors.forename: Joan E
authors.initials: JE
authors.lastname: Landon
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 1620 Tremont Street, Suite 3030, Boston, MA, 02120, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Fischer
mesh_terms: D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D055118:Medication Adherence / Q000523:psychology; D008875:Middle Aged; D012044:Regression Analysis; D012189:Retrospective Studies; D014481:United States; D016903:Drug Monitoring
chemical_list: D000959:Antihypertensive Agents
keywords: cardiovascular diseases; hypertension; medication adherence; medication persistence