Abstract
BACKGROUND: Patients with hypertension and cardiovascular disease (CVD), diabetes, or chronic kidney disease (CKD) usually require two or more antihypertensive agents to achieve blood pressure (BP) goals. METHODS: The efficacy/safety of olmesartan (OM) 40 mg, amlodipine besylate (AML) 10 mg, and hydrochlorothiazide (HCTZ) 25 mg versus the component dual-combinations (OM 40/AML 10 mg, OM 40/HCTZ 25 mg, and AML 10/HCTZ 25 mg) was evaluated in participants with diabetes, CKD, or chronic CVD in the Triple Therapy with Olmesartan Medoxomil, Amlodipine, and Hydrochlorothiazide in Hypertensive Patients Study (TRINITY). The primary efficacy end point was least squares (LS) mean reduction from baseline in seated diastolic BP (SeDBP) at week 12. Secondary end points included LS mean reduction in SeSBP and proportion of participants achieving BP goal (<130/80 mm Hg) at week 12 (double-blind randomized period), and LS mean reduction in SeBP and BP goal achievement at week 52/early termination (open-label period). RESULTS: At week 12, OM 40/AML 10/HCTZ 25 mg resulted in significantly greater SeBP reductions in participants with diabetes (-37.9/22.0 mm Hg vs -28.0/17.6 mm Hg for OM 40/AML 10 mg, -26.4/14.7 mm Hg for OM 40/HCTZ 25 mg, and -27.6/14.8 mm Hg for AML 10/HCTZ 25 mg), CKD (-44.3/25.5 mm Hg vs -39.5/23.8 mm Hg for OM 40/AML 10 mg, -25.3/17.0 mm Hg for OM 40/HCTZ 25 mg, and -33.4/20.6 mm Hg for AML 10/HCTZ 25 mg), and chronic CVD (-37.8/20.6 mm Hg vs -31.7/18.2 mm Hg for OM 40/AML 10 mg, -30.9/17.1 mm Hg for OM 40/HCTZ 25 mg, and -27.5/16.1 mm Hg for AML 10/HCTZ 25 mg) (P<0.05 for all subgroups vs dual-component treatments). BP goal achievement was greater for participants receiving triple-combination treatment compared with the dual-combination treatments, and was achieved in 41.1%, 55.0%, and 38.9% of participants with diabetes, CKD, and chronic CVD on OM 40/AML 10/HCTZ 25 mg, respectively. At week 52, there was sustained BP lowering with the OM/AML/HCTZ regimen. Overall, the triple combination was well tolerated. CONCLUSIONS: In patients with diabetes, CKD, or chronic CVD, short-term (12 weeks) and long-term treatment with OM 40/AML 10/HCTZ 25 mg was well tolerated, lowered BP more effectively, and enabled more participants to reach BP goal than the corresponding 2-component regimens. TRIAL IDENTIFICATION NUMBER: NCT00649389.