Triple Combination Therapy Significantly Better than Dual Therapy for Hypertension

Results from a phase 3, multicenter study of triple- versus dual-combination, fixed-dose antihypertensive therapy in patients with moderate to severe hypertension showed superiority for triple-combination therapy….

Lead author Suzanne Oparil, MD, University of Alabama at Birmingham, noted that hypertension is controlled in only about half of US patients under treatment. “There is a need to have a multi-drug regimen for resistant high blood pressure that attacks the volume problem with a diuretic, that blocks the rennin-angiotensin-aldosterone system with an ARB [angiotensin receptor blocker], and that further lowers blood pressure with a calcium channel blocker.”

The study objective was to compare coadministration of olmesartan medoxomil 40 mg plus amlodipine 10 mg and hydrochlorothiazide (HCTZ) 25 mg (n = 627) versus olmesartan medoxomil/amlodipine (n = 628), olmesartan medoxomil/HCTZ (n = 637), and amlodipine/HCTZ (n = 600).

The primary endpoint was change from baseline to week 12 in diastolic blood pressure (DBP) for olmesartan medoxomil/amlodipine/HCTZ versus the corresponding dual treatments.

Treatment with olmesartan medoxomil plus amlodipine plus HCTZ resulted in significantly greater mean reductions in DBP (21.8 vs 15.1-18.0 mm Hg) and systolic blood pressure (37.1 vs 27.5-30.0 mm Hg) than corresponding therapy with 2-drug combinations.

The differences were reported after 12 weeks of therapy and at earlier measurements after 6, 8, and 10 weeks (P < .0001, all comparisons).

In addition, a significantly greater percentage of patients treated with olmesartan medoxomil plus amlodipine plus HCTZ than with dual components reached the blood pressure target of <140/90 mm Hg (69.9% vs 41.1%-53.4%; P < .0001, all comparisons).

Subgroup analyses showed percentages of patients reaching blood pressure target with triple versus dual therapy to be significantly greater regardless of gender, age, race, or hypertension severity. In addition, 24-hour ambulatory blood pressure monitoring revealed consistently greater effects for triple therapy.

Serious adverse events were low for all regimens (1.2%-1.7%), with few withdrawals attributed to treatment-related events (0.7% for olmesartan medoxomil/amlodipine; 3.1% for olmesartan medoxomil/amlodipine/HCTZ). Peripheral oedema was higher in the amlodipine-containing regimens (7.0%-8.3% vs 1.0% for olmesartan medoxomil/HCTZ). All regimens were similarly well tolerated in the subgroups.

“This is a very potent way of lowering blood pressure — appropriate for patients who are already on 1 or 2 antihypertensive medications,” concluded Dr. Oparil.

Presented May 2, 2010. [Presentation title: Efficacy and Safety of Combination Olmesartan Medoxomil Plus Amlodipine Besylate Plus Hydrochlorothiazide in Patients With Hypertension: The TRINITY Study. Abstract PO-57]