Combined Olmesartan, Amlodipine, and Hydrochlorothiazide Therapy in Randomized Patients with Hypertension: A Subgroup Analysis of the TRINITY Study by Age

Abstract

BackgroundHypertension is often inadequately controlled in older people.ObjectiveThis prespecified subgroup analysis assessed the efficacy and safety of an olmesartan medoxomil (OM) 40 mg/amlodipine besylate (AML) 10 mg/hydrochlorothiazide (HCTZ) 25 mg triple-combination treatment compared with the 3 components as dual-combination treatments in participants with hypertension who were <65 and ≥65 years of age. Within the ≥65 years of age subgroup, efficacy and safety were also summarized for participants ≥75 years of age.Study design12-week, multicenter, double-blind, randomized, parallel-group study.Setting317 ambulatory care sites in the US and Puerto Rico.ParticipantsIndividuals ≥18 years of age with mean seated blood pressure (SeBP) ≥140/100 or ≥160/90 mmHg off antihypertensive medication on 2 consecutive clinic visits with no recent history of significant cerebrovascular disease, coronary artery disease, heart failure (New York Heart Association class III or IV), severe renal insufficiency, or uncontrolled diabetes (HbA1c >9 %).InterventionParticipants were randomized, stratified by age, diabetes status, and race to one of four treatment assignments: OM 40/AML 10/HCTZ 25 mg, OM 40/AML 10 mg, OM 40/HCTZ 25 mg, or AML 10/HCTZ 25 mg.Main Outcome MeasureLeast squares (LS) mean change from baseline in seated diastolic blood pressure (SeDBP) at week 12 (last observation carried forward) in each age subgroup (prespecified analysis).ResultsOf the 2492 randomized participants in the study (total cohort), 2021 (81.1 %) were <65 and 471 (18.9 %) were ≥65 years of age, including 79 (3.2 %) who were ≥75 years of age. OM 40/AML 10/HCTZ 25 mg triple-combination treatment resulted in a significantly greater reduction in LS mean SeDBP at week 12 than dual-combination component treatments in participants in both cohorts: <65 years (21.0 vs. 14.2–17.2 mmHg; p < 0.0001) and ≥65 years (23.7 vs. 17.3–20.0 mmHg; p ≤ 0.002). Similarly, triple-combination treatment resulted in a greater reduction in LS mean seated systolic blood pressure (SeSBP) at week 12 than dual-combination component treatments: <65 years (38.2 vs. 28.3–31.4 mmHg; p < 0.0001) and ≥65 years (39.2 vs. 29.3–31.1 mmHg; p < 0.0001). Triple-combination treatment was more effective than dual-combination treatments in enabling participants to reach SeBP goal (<140/90 mmHg [<130/80 mmHg in participants with diabetes, chronic kidney disease, or chronic cardiovascular disease]) in both age subgroups (<65 years: 65 vs. 34–50 %, respectively, p < 0.0001 and ≥65 years: 63 vs. 32–39 %; p ≤ 0.0004). All 4 treatments were safe and well tolerated with low discontinuation rates in both age subgroups. There were no clinically relevant differences in the incidence of treatment-emergent adverse events between participants <65 and ≥65 years of age receiving triple-combination treatment.ConclusionTriple-combination treatment with OM 40/AML 10/HCTZ 25 mg was well tolerated and more effective in lowering BP than the component dual-combination treatments in elderly and non-elderly subgroups.

Efficacy and Tolerability of Triple‐Combination Therapy With Olmesartan, Amlodipine, and Hydrochlorothiazide: A Subgroup Analysis of Patients Stratified by Hypertension Severity, Age, Sex, and Obesity

“…The study showed that triple therapy was more effective in reducing BP than the component dual therapies, and a subsequent open‐label extension showed that reductions in BP were maintained over the long term (52 weeks) . Subgroup analyses from TRINITY have also shown that the improved efficacy of triple therapy was seen in major subgroups of patients, including those with diabetes, chronic kidney disease, or chronic CV disease, as well as those of black or Hispanic/Latino origin, those with advanced age, or those with obesity . The study by Volpe and colleagues showed that triple therapy is more effective than dual therapy at lowering BP across a range of doses.…”

Efficacy and Safety Study of Olmesartan Medoxomil, Amlodipine, and Hydrochlorothiazide Combination Therapy in Patients with Hypertension Not Controlled with Olmesartan Medoxomil and Hydrochlorothiazide Combination Therapy: Results of a Randomized, Double-Blind, Multicenter Trial

“…The triple combination regimen with OM/AML/HCTZ, including high-dose OM 40 mg, was associated with significant BP reductions compared with any of the dual combination regimens at week 12 in the phase III TRINITY (triple therapy with olmesartan medoxomil, amlodipine besylate, and hydrochlorothiazide in adult patients with hypertension) study [ 10 , 11 ]. According to the subgroup analyses of the TRINITY trial, OM/AML/HCTZ was more effective for BP reductions than each of the dual regimens, irrespective of hypertension severity, age, or sex [ 10 , 12 ]. Other clinical studies reported that a triple combination of OM/AML/HCTZ provides effective BP reduction in patients whose BP is not controlled with a dual combination of OM/AML [ 13 , 14 ].…”

Management of the Spectrum of Essential Hypertension: A 2013 Perspective

“…A recent study found that a three-drug combination of ARB, CCB and HCTZ was more effective in achieving BP control when compared to a two-drug combination of the given classes (ARB/CCB, ARB/HCTZ, CCB/HCTZ). The regimen was well tolerated and effective in both elderly (≥ 65) and non-elderly (<65) groups [57].…”