title: Patient Adherence to Olmesartan/Amlodipine Combinations: Fixed Versus Extemporaneous Combinations.
abstract: BACKGROUND
  Lack of adherence to prescribed therapies is often a cause of suboptimal blood pressure control in patients with hypertension. To enhance patients' adherence to treatment, fixed-dose combinations of active substances with complementary mechanisms of action have been developed. An angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker (ARB) is often combined with a calcium channel blocker. Olmesartan is the most used ARB in combination therapy. In Italy, in September 2011, a fixed-dose combination of olmesartan/amlodipine (olmesartan/amlodipine 20/5 mg, 40/5 mg, or 40/10 mg) was introduced to treat patients with hypertension for whom control of blood pressure is not reached with either olmesartan or amlodipine alone. Prior research on adherence to olmesartan/amlodipine combinations was carried out in local contexts (e.g., claims databases of Italian regions or local health authorities), and/or it was limited by the fact that adherence was assessed against monotherapies already known for their low compliance profile, such as diuretics.
  
  
  OBJECTIVE
  To compare adherence with olmesartan/amlodipine fixed-dose combination (FDC) and extemporaneous combination in primary care in Italy.
  
  
  METHODS
  A nationwide, population-based study was conducted by using the Health Search IMS Health Longitudinal Patient Database. Patients aged > 17 years, affected by hypertension and treated with the FDC or extemporaneous combination of olmesartan/amlodipine, were identified. Adherence to these 2 therapeutic regimens was estimated by calculating the proportion of days covered (PDC). Patients were classified into 3 levels of adherence: high (PDC ≥ 80%), intermediate (PDC = 40%-79%), or low (PDC < 40%).
  
  
  RESULTS
  In the 6-month follow-up, FDC showed higher adherence compared with an extemporaneous combination (55.1% vs. 15.9%, P < 0.001). This difference was confirmed in a multivariable logistic regression model clustered on patient identifier (odds ratio = 6.65; 95% CI = 3.10-14.26; P < 0.001). The proportion of patients adherent to FDC varied from 60.4% for the 40/5 mg formulation to 47.5% for the 40/10 mg formulation.
  
  
  CONCLUSIONS
  These findings suggest that higher adherence may be achieved with FDCs than with extemporaneous combinations. To improve the degree of adherence, general practitioners may consider prescribing fixed combinations of antihypertensive agents as soon as monotherapies fail to achieve the expected therapeutic objective.
authors.affiliation: 1 Research Fellow, Department of Health Sciences, University of Florence, Florence, Italy.
authors.forename: Miriam
authors.initials: M
authors.lastname: Levi
authors.affiliation: 2 Chief Statistician, Health Search, Italian College of General Practitioners and Primary Care, Florence, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pasqua
authors.affiliation: 3 General Director, Health Search, Italian College of General Practitioners and Primary Care, Florence, Italy.
authors.forename: Iacopo
authors.initials: I
authors.lastname: Cricelli
authors.affiliation: 4 President, Italian College of General Practitioners and Primary Care, Florence, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Cricelli
authors.affiliation: 5 Postdoctoral Researcher, Department of Medical and Surgical Sciences-Pharmacology Unit, University of Bologna, Bologna, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Piccinni
authors.affiliation: 6 General Practitioner, Italian College of General Practitioners and Primary Care, Florence, Italy.
authors.forename: Damiano
authors.initials: D
authors.lastname: Parretti
authors.affiliation: 7 Research Director, Health Search, Italian College of General Practitioners and Primary Care, Florence, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Lapi
mesh_terms: D000368:Aged; D017311:Amlodipine / Q000008:administration & dosage*; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001794:Blood Pressure / Q000187:drug effects; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D007093:Imidazoles / Q000008:administration & dosage*; D008297:Male; D055118:Medication Adherence; D013777:Tetrazoles / Q000008:administration & dosage*
chemical_list: D000959:Antihypertensive Agents; D007093:Imidazoles; D013777:Tetrazoles; D017311:Amlodipine; C437965:olmesartan