Olmesartan Medoxomil Plus Amlodipine Increases Efficacy in Patients with Moderate-to-severe Hypertension After Monotherapy: a Randomized, Double-blind, Parallel-group, Multicentre Study

Background And Objective: Hypertension remains a major global health problem, and evidence suggests that the majority of patients will require two or more antihypertensive agents in order to reach specified BP targets. Combining two drugs from different classes has the potential to target different aspects of hypertension, which may result in additional BP decreases compared with either agent used alone. This randomized, double-blind, parallel-group, multicentre trial in patients with moderate-to-severe hypertension (systolic BP [SBP]/diastolic BP [DBP] > or =160/100 mmHg) investigated the additional efficacy in BP reduction and BP goal rates (<140/90 mmHg for patients without diabetes mellitus, <130/80 mmHg for patients with diabetes) achieved by adding amlodipine 5 or 10 mg/day to olmesartan medoxomil (hereafter olmesartan) 20 mg/day in patients not adequately controlled on olmesartan monotherapy.

Methods: After 8 weeks' open-label olmesartan 20 mg monotherapy, 538 patients with SBP/DBP > or =140/90 mmHg were randomized to 8 weeks' double-blind therapy with olmesartan/placebo, olmesartan/amlodipine 20 mg/5 mg or olmesartan/amlodipine 20 mg/10 mg. This trial is registered on the www.clinicaltrials.gov website (NCT00220220).

Results: After 8 weeks (with last observation carried forward), the adjusted mean change in seated DBP (SeDBP) from baseline was -7.6 mmHg for olmesartan/placebo, -10.4 mmHg for olmesartan/amlodipine 20 mg/5 mg (p = 0.0006 vs olmesartan/placebo) and -10.9 mmHg for olmesartan/amlodipine 20 mg/10 mg (p < 0.0001 vs olmesartan/placebo). Mean changes in SeSBP from baseline with olmesartan/amlodipine 20 mg/5 mg and olmesartan/amlodipine 20 mg/10 mg were -16.1 and -16.7 mmHg, respectively (p < 0.0001 for both dose regimens vs olmesartan/placebo). BP goal rates were significantly higher with olmesartan/amlodipine 20 mg/5 mg and olmesartan/amlodipine 20 mg/10 mg (44.5% and 45.8%, respectively; p = 0.0011 and p = 0.0004, respectively) versus olmesartan/placebo (28.5%). Combination therapy was well tolerated, and the incidence of drug-related adverse events was 8.9% for olmesartan/placebo, 7.7% for olmesartan/amlodipine 20 mg/5 mg, and 11.3% for olmesartan/amlodipine 20 mg/10 mg (p = 0.490). Most adverse events were mild in severity and were well known drug-class issues.

Conclusions: Combining olmesartan and amlodipine resulted in significantly greater BP lowering in patients not achieving adequate BP control with olmesartan monotherapy, thus allowing a significantly greater proportion of patients to achieve BP goal.