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

Background Hypertension is often inadequately controlled in older people. Objective This 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 design 12-week, multicenter, double-blind, randomized, parallel-group study. Setting 317 ambulatory care sites in the US and Puerto Rico. Participants Individuals ≥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 (HbA 1c >9 %). Intervention Participants 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 Measure Least 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). Results Of 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. Conclusion Triple-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.