Efficacy and safety of olmesartan medoxomil 40 mg/hydrochlorothiazide 12.5 mg combination therapy versus olmesartan medoxomil 40 mg monotherapy in patients with moderate to severe hypertension: a randomized, double-blind, parallel-group, multicentre, multinational, phase III study.

backgroundCurrent hypertension guidelines recommend using two antihypertensive agents when blood pressure (BP) control is not achieved with one single agent.

objectiveThis study was designed to assess the antihypertensive benefit of the olmesartan medoxomil 40 mg/hydrochlorothiazide (HCTZ) 12.5 mg combination versus olmesartan medoxomil 40 mg monotherapy in patients with moderate to severe hypertension.

methodsThis was a randomized, double-blind, parallel-group, up-titration, multicentre, multinational, phase III study. Following a 2-week single-blind placebo run-in phase, 846 hypertensive patients with mean seated systolic BP (SeSBP) of 160-200 mmHg and mean seated diastolic BP (SeDBP) of 100-120 mmHg were randomized (1 : 2 ratio) to receive double-blind treatment with olmesartan medoxomil 40 mg or olmesartan medoxomil 40 mg/HCTZ 12.5 mg for 8 weeks (phase A). At week 8, patients not reaching BP goal (<140/90 mmHg; <130/80 mmHg in patients with diabetes mellitus) were up-titrated from olmesartan medoxomil 40 mg to olmesartan medoxomil 40 mg/HCTZ 12.5 mg or from olmesartan medoxomil 40 mg/HCTZ 12.5 mg to olmesartan medoxomil 40 mg/HCTZ 25 mg for an additional 8 weeks (phase B). Patients on goal continued their initial treatment. The primary efficacy parameter was the change in mean SeDBP during phase A.

resultsOlmesartan medoxomil 40 mg/HCTZ 12.5 mg reduced mean SeDBP significantly more (-18.9 mmHg) than olmesartan medoxomil 40 mg (-15.8 mmHg) after 8 weeks of double-blind treatment (difference: -3.1 mmHg, p < 0.0001). Olmesartan medoxomil 40 mg/HCTZ 12.5 mg also reduced mean SeSBP significantly more than olmesartan medoxomil 40 mg (-5.4 mmHg, p < 0.0001). As a result, BP goal rates at week 8 were significantly higher with olmesartan medoxomil 40 mg/HCTZ 12.5 mg than with olmesartan medoxomil 40 mg (58.5% vs 44.3%; odds ratio 1.88; 95% CI 1.32, 2.54). During phase B, mean BP reductions were greater in patients up-titrated from olmesartan medoxomil 40 mg to olmesartan medoxomil 40 mg/HCTZ 12.5 mg than in those continuing on olmesartan medoxomil 40 mg (SeDBP: -9.3 mmHg vs -0.5 mmHg; SeSBP: -12.4 mmHg vs -0.5 mmHg). Similarly, mean BP reductions were greater in patients up-titrated from olmesartan medoxomil 40 mg/HCTZ 12.5 mg to olmesartan medoxomil 40 mg/HCTZ 25 mg than in those continuing on olmesartan medoxomil 40 mg/HCTZ 12.5 mg (SeDBP: -8.0 mmHg vs -0.3 mmHg; SeSBP: -12.1 mmHg vs -0.4 mmHg). In patients not on goal at week 8, addition of HCTZ 12.5 mg to olmesartan medoxomil 40 mg or up-titration from olmesartan medoxomil 40 mg/HCTZ 12.5 mg to olmesartan medoxomil 40 mg/HCTZ 25 mg brought additional patients to goal at week 16 (38.8% vs 36.9%). All treatments were well tolerated.

conclusionThe olmesartan medoxomil 40 mg/HCTZ 12.5 mg combination is superior to olmesartan medoxomil 40 mg monotherapy in reducing SeDBP and SeSBP and increasing BP goal rates after 8 weeks. Patients not on goal at week 8 with olmesartan medoxomil 40 mg or olmesartan medoxomil 40 mg/HCTZ 12.5 mg benefited from adding HCTZ 12.5 mg or up-titrating to olmesartan medoxomil 40 mg/HCTZ 25 mg, respectively, confirming that up-titration is a clinically meaningful way to improve BP control. [ TRIAL REGISTRATION NUMBER: NCT00441350 (ClinicalTrials.gov Identifier)].