Olmesartan/amlodipine: a review of its use in the management of hypertension

Abstract

Combination therapy is an effective strategy to increase antihypertensive efficacy in those patients with poor blood pressure (BP) control. In order to achieve BP targets, at least 75% of patients may require combination therapy, and European guidelines advocate this approach, particularly in those patients with a high cardiovascular risk. Evidence from large, randomized controlled trials, and the European hypertension treatment guidelines is supportive of the use of an angiotensin receptor blocker (ARB) with a calcium channel blocker (CCB). Fixed-dose combination formulations of olmesartan medoxomil, an ARB, and the CCB amlodipine are approved in several European countries for patients with essential hypertension. The olmesartan/amlodipine combination has demonstrated greater efficacy than its component monotherapies in reducing BP in patients with mild-to-severe hypertension. Significantly greater reductions in seated diastolic BP were observed between baseline and after eight weeks of treatment with olmesartan/amlodipine, compared with equivalent doses of olmesartan or amolodipine monotherapy (P < 0.001), in the factorial Combination of Olmesartan Medoxomil and Amlodipine Besylate in Controlling High Blood Pressure (COACH) trial. About 85% of the maximal BP reductions after the 8-week treatment period were already observed after two weeks. Uptitration as necessary, with or without hydrochlorothiazide, allowed the majority of patients to achieve BP control in a 44-week open-label extension treatment period to the COACH trial. The use of olmesartan/amlodipine allowed up to 54% of patients, with previously inadequate responses to amlodipine or olmesartan monotherapy, to achieve their BP goals. Data from post-registration studies using tight BP control and forced titration regimens have further demonstrated the high efficacy of olmesartan/amlodipine in achieving BP goal rates. Moreover, consistent reductions in BP were observed over the 24-hour dosing interval using ambulatory measurements. Olmesartan/amlodipine was generally well tolerated over the short- and long-term, with a lower frequency of peripheral edema with olmesartan/amlodipine 40/10 mg than with amlodipine 10 mg monotherapy.

Keywords: BP control; BP goals; antihypertensive monotherapy; combination therapy; hypertension; patients.

Figure 1

Mean change in seated systolic blood pressure (SeSBP) from baseline to weeks 2, 4, 6 and 8 with olmesartan (OLM) and amlodipine (AML) monotherapy and olmesartan/amlodipine combination therapy. Notes: Based upon data presented by Chrysant et al., For clarity, some dosages and combinations have been omitted from this Figure.

Figure 2

Olmesartan/amlodipine combination therapy versus amlodipine monotherapy – mean change from baseline in seated blood pressure after eight weeks of randomized, double-blind treatment. Notes: *p < 0.05; **p < 0.0001 vs AML 5 mg monotherapy. Abbreviations: AML, amlodipine; OLM, olmesartan; SeBP, seated blood pressure; SeDBP, seated diastolic blood pressure; SeSBP, seated systolic blood pressure.

Figure 3

Olmesartan/amlodipine combination therapy versus amlodipine monotherapy – mean change from baseline in seated systolic blood pressure after eight weeks of randomized, double-blind, uptitrated treatment. Notes: ^†Uptitration of non-responders: patients whose BP was not adequately controlled (SeDBP ≥90 mmHg and SeSBP ≥140 mmHg) during randomized treatment in Period II. Abbreviations: AML, amlodipine; OLM, olmesartan; SeSBP, seated systolic blood pressure.

Figure 4

Mean levels of seated systolic blood pressure (SeSBP) at the start (week 0) and end of treatment (week 52) according to baseline SeSBP in all patients treated with olmesartan/amlodipine combination therapy in a randomized, double-blind study. Note: Adapted with permission from Mourad and Le Joune. Effective systolic blood pressure reduction with olmesartan medoxomil/amlodipine combination therapy. Clin Drug Investig. 2009;29(6):419–425.

Figure 5

Proportion of patients who achieved the cumulative seated blood pressure (SeBP) goal of 140/90 mmHg in the BP-CRUSH study. Abbreviations: AML, amlodipine; HCTZ, hydrochlorothiazide; OLM, olmesartan.