title: Compliance, safety, and effectiveness of fixed-dose combinations of antihypertensive agents: a meta-analysis.
abstract: 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.
authors.affiliation: International Centre for Circulatory Health, Imperial College London, London, United Kingdom. A.K.Gupta@imperial.ac.uk
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Gupta
authors.forename: Shazia
authors.initials: S
authors.lastname: Arshad
authors.forename: Neil R
authors.initials: NR
authors.lastname: Poulter
mesh_terms: D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001795:Blood Pressure Determination; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D010349:Patient Compliance / Q000706:statistics & numerical data*; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D017751:Safety Management; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D004338:Drug Combinations