Compliance, safety, and effectiveness of fixed-dose combinations of antihypertensive agents: a meta-analysis

Hypertension. 2010 Feb;55(2):399-407. doi: 10.1161/HYPERTENSIONAHA.109.139816. Epub 2009 Dec 21.


Two or more antihypertensive agents are increasingly used to control blood pressure (BP) in hypertensive patients. However, it is unclear whether fixed-dose combinations (FDCs) of 2 antihypertensive agents in a single tablet provide greater benefits than the corresponding free-drug components given separately. A meta-analysis was performed to assess compliance, persistence, BP control, and safety associated with FDCs in comparison with their free-drug components. Fifteen included studies (n=32331) reported on >or=1 of the evaluated outcomes. In 3 cohort studies and 2 trials reporting on drug compliance (n=17 999), the use of FDCs was associated with significantly better compliance (odds ratio: 1.21 [95% CI: 1.03 to 1.43]; P=0.02) compared with its corresponding free-drug combinations. In 3 cohort studies (n=12 653), there was a nonsignificant improvement in persistence with therapy (odds ratio: 1.54 [95% CI: 0.95 to 2.49]; P=0.08), and in 5 trials (n=1775) the odds ratio for adverse effects for FDC use compared with free-drug combination use was 0.80 (95% CI: 0.58 to 1.11; P=0.19). In 9 trials (n=1671) with BP data, use of an FDC was associated with nonsignificant changes in systolic and diastolic BPs of 4.1 mm Hg (95% CI: -9.8 to 1.5; P=0.15) and 3.1 mm Hg (95% CI: -7.1 to 0.9; P=0.13), respectively. In these BP-lowering comparisons, there was heterogeneity associated with differences in study design but no publication bias. In conclusion, compared with free-drug combinations, FDCs of antihypertensive agents are associated with a significant improvement in compliance and with nonsignificant beneficial trends in BP and adverse effects.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antihypertensive Agents / administration & dosage*
  • Blood Pressure Determination
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Combinations*
  • Female
  • Humans
  • Hypertension / diagnosis
  • Hypertension / drug therapy*
  • Male
  • Patient Compliance / statistics & numerical data*
  • Prognosis
  • Randomized Controlled Trials as Topic
  • Safety Management
  • Treatment Outcome


  • Antihypertensive Agents
  • Drug Combinations