Levi, M; Pasqua, A; Cricelli, I; Cricelli, C; Piccinni, C; Parretti, D; Lapi, F
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.
DISCLOSURES: This study was funded by Menarini Farmaceutici Riuniti. The funding institution had no role in the design, analysis, and interpretation of the results. Lapi and Cricelli provided consultancies in protocol preparation for epidemiological studies and data analyses for IBSA and Bayer. Cricelli and Parretti provided clinical consultancies for IBSA, Bayer, and Alfa Wasserman. Levi, Pasqua, and Piccinni have no conflicts of interest to disclose. Study design was contributed by C. Cricelli and Lapi, with assistance from the rest of the authors. Pasqua and I. Cricelli took the lead in data collection, assisted by the other authors, and data interpretation was performed by Levi, Piccinni, and Lapi, with assistance from the other authors. The manuscript was written primarily by Levi and Paretti, with assistance from the other authors, and revised by I. Cricelli, C. Cricelli, and Lapi, assisted by the other authors.