Long‐Term Efficacy and Safety of Triple‐Combination Therapy With Olmesartan Medoxomil and Amlodipine Besylate and Hydrochlorothiazide for Hypertension

Abstract

Most patients with hypertension require combination therapy in order to achieve blood pressure (BP) goals. This 40-week open-label extension of the 12-week double-blind Triple Therapy With Olmesartan Medoxomil, Amlodipine, and Hydrochlorothiazide in Hypertensive Patients Study (TRINITY) evaluated the efficacy and safety of triplecombination treatments with olmesartan medoxomil, amlodipine besylate, and hydrochlorothiazide (OM ⁄ AML ⁄ HCTZ) in 2112 participants with moderate to severe hypertension. Following 2 weeks of initial treatment with OM 40 ⁄ AML 5 ⁄ HCTZ 12.5 mg, participants not achieving BP goal were titrated to OM 40 ⁄ AML 5 ⁄ HCTZ 25 mg or OM 40 ⁄ AML 10 ⁄ HCTZ 12.5 mg on a randomized basis. At week 16, participants who did not achieve BP goal were further titrated to OM 40 ⁄ AML 10 ⁄ HCTZ 25 mg. At the end of the study, 44.5% to 79.8% of participants reached BP goal and the mean BP decreased from 168.6 ⁄ 100.7 mm Hg (baseline BP at randomization) to 125.0 to 136.8 mm Hg ⁄ 77.8 to 82.5 mm Hg, depending on treatment. Longterm treatment with OM ⁄ AML ⁄ HCTZ was well tolerated and effective with no new safety concerns.

Effectiveness of Carvedilol versus Indapamide in Uncontrolled Diabetic Hypertensive Patients being Treated with Olmesartan and Amlodipine

“…Adverse effects reported in our study were mild and well tolerated and no discontinuation was needed. Several previous studies also showed well tolerability of triple drug combination 13,20 .…”

“…Therefore, adding thiazide-like diuretics [such as Chlortalidone (12.5-25.0 mg once daily) or Indapamide (1.5 mg modified-release or 2.5 mg once daily)] is suitable as a third-line agent introduced at Step 314. In a study Kereiakes et al 20 Adding another class of medication would be an alternative strategy, although the guidelines do not indicate clearly the third choice for uncontrolled hypertension. In these patients, -blockers seem to be more effective than increasing the dose of either ACE inhibitors or CCB 13 .…”

Adherence and Health Care Costs with Single-Pill Fixed-Dose Combinations in Hypertension Management

“…In an open-label extension of the randomized trial with olmesartan, amlodipine, and hydrochlorothiazide, all study participants were switched to the triple-drug combination at the conclusion of their 12-week double-blind treatment period and were followed for an additional 40 weeks. 60 No new safety concerns were identified, and 55% and 64% of study participants achieved their BP goal within 2 weeks of starting and by the end of the open-label period/early termination, respectively. Mean BP reduction at the end of the open-label period/ early termination was comparable with that seen in study participants receiving triple-drug therapy during the double-blind treatment period, demonstrating the safety, antihypertensive efficacy, and durability of this triple-drug combination.…”

“…Mean BP reduction at the end of the open-label period/ early termination was comparable with that seen in study participants receiving triple-drug therapy during the double-blind treatment period, demonstrating the safety, antihypertensive efficacy, and durability of this triple-drug combination. 60 In the open-label study evaluating aliskiren, amlodipine, and hydrochlorothiazide, this triple-combination therapy was shown to be well tolerated and efficacious as a treatment for up to 54 weeks in patients with hypertension. 61 As a result of these evaluations, the U.S. Food and Drug Administration has approved all 3 of these triple-drug combinations for the management of hypertension as single-pill fixed-dose formulations in patients not controlled on dual therapy.…”

Renin-angiotensin system in the kidney: What is new?

“…In this case, the most commonly used drugs are ARBs and ACE inhibitors, Ca 2+ channel blockers (CCB) and diuretics [130] . Long-term treatment triple therapy with olmesartan medoxomil (ARB), amlodipine besylate (CCB) and hydrochlorothiazide (diuretic) in 2112 hypertensive patients with moderate to severe hypertension resulted in 44.5%-79.8% of participants having a decreased the mean blood pressure from 168.6/100.7 mm Hg to 125.0-136.8/77.8-82.5 mmHg, reaching the blood pressure goal [133] . The same triple therapy also proved to be efficient in hypertensive Hispanic/Latin patients [134] .…”