Improved persistence and adherence to diuretic fixed-dose combination therapy compared to diuretic monotherapy

BMC Fam Pract. 2008 Nov 6;9:61. doi: 10.1186/1471-2296-9-61.


Background: Diuretics are recommended as initial treatment for hypertension. Several studies have suggested suboptimal persistence and adherence to thiazide diuretic monotherapy; this study compared patient persistence and adherence with hydrochlorothiazide (HCTZ) monotherapy to fixed-dose combinations containing HCTZ.

Methods: Patients with at least one prescription claim during 2001 to 2003 for either HCTZ or one of the following fixed-dose combinations: angiotensin-receptor blockers/HCTZ (ARB/HCTZ), angiotensin-converting enzyme inhibitor/HCTZ (ACEI/HCTZ), or beta blockers/HCTZ (BB/HCTZ) were identified. Patients were required to be continuously benefit-eligible six months pre- and one year post-index date, and to have no prescription claims for any antihypertensive therapy six months prior to the index date. Patients were followed for one year to assess persistence, medication possession ratio (MPR), adherence (MPR >80%), and proportion of days covered (PDC) with initial antihypertensive therapy. Logistic regression was used to calculate adjusted odds ratios for persistence, adherence and PDC, adjusted for age, gender, business segment, RxRisk disease categories, average co-pay and concurrent cardiovascular-related medication utilization.

Results: The study cohort consisted of 48,212 patients; 72.5% used HCTZ, 13.2% ACEI/HCTZ, 9.3% ARB/HCTZ, and 5.0% BB/HCTZ. Mean age was 53.7 years and 66.5% were female. A significantly lower proportion of patients using HCTZ (29.9%) remained persistent with therapy at 12 months compared with ARB/HCTZ (52.6%; OR = 0.37, CI = 0.36, 0.38), ACEI/HCTZ (51.4%; OR = 0.38, CI = 0.37, 0.39), and BB/HCTZ (51.9%; OR = 0.38, 0.37, 0.40). Similarly, PDC was lower for HCTZ patients (32.5%) as compared to ARB/HCTZ (53.7%; OR = 0.39, CI = 0.37, 0.40), ACEI/HCTZ (50.9%; OR = 0.42, CI = 0.40, 0.43), and BB/HCTZ (51.3%; OR = 0.44, CI 0.42, 0.45). MPR was also significantly lower for HCTZ patients as compared to those using fixed-dose combination therapies.

Conclusion: Initiating HCTZ fixed-dose combination therapy with an ACEI, ARB, or BB was associated with greater persistence and adherence as compared to HCTZ monotherapy. Further research is needed to determine the relationship between improved persistence and adherence with blood pressure control.

MeSH terms

  • Adrenergic beta-Antagonists / administration & dosage
  • Angiotensin II Type 1 Receptor Blockers / administration & dosage
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage
  • Antihypertensive Agents / administration & dosage*
  • Cohort Studies
  • Diuretics / administration & dosage*
  • Drug Therapy, Combination
  • Female
  • Humans
  • Hydrochlorothiazide / administration & dosage*
  • Male
  • Medication Adherence / statistics & numerical data
  • Middle Aged
  • Proportional Hazards Models
  • Retrospective Studies
  • Time Factors
  • Treatment Outcome


  • Adrenergic beta-Antagonists
  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Diuretics
  • Hydrochlorothiazide