Efficacy of Amlodipine/Olmesartan Medoxomil ± Hydrochlorothiazide in Patients Aged ≥ 65 or < 65 Years With Uncontrolled Hypertension on Prior Monotherapy

Abstract

Our subanalysis evaluated the efficacy of an amlodipine/olmesartan medoxomil (AML/OM)-based titration regimen to achieve blood pressure (BP) goals among patients aged ≥ 65 years. In this dose-titration study, 999 patients (228 of whom were aged ≥ 65 years) with uncontrolled BP after ≥ 1 month of monotherapy were switched to fixed-dose AML/OM 5/20 mg and uptitrated every 4 weeks to AML/OM 5/40 and 10/40 mg to achieve BP < 120/70 mm Hg. Patients were subsequently uptitrated every 4 weeks to AML/OM 10/40 mg + hydrochlorothiazide (HCTZ) 12.5 mg and AML/OM 10/40 mg + HCTZ 25 mg to achieve BP < 125/75 mm Hg. The primary efficacy endpoint (ie, the cumulative percentage of patients achieving the seated cuff systolic BP goal of < 140 mm Hg [or < 130 mm Hg for patients with type 2 diabetes mellitus] during first 12 weeks of treatment) was achieved by 76.7% and 75.6% of patients aged ≥ 65 (ie, 65-80) years and < 65 (ie, 18-64) years, respectively. For patients aged ≥ 65 and < 65 years, mean seated cuff BP changes from baseline during the titration periods ranged from -14.5/-7.8 mm Hg and -14.1/-7.7 mm Hg, respectively, for AML/OM 5/20 mg, to -28.5/-12.4 and -24.5/-14.0 mm Hg for AML/OM 10/40 mg + HCTZ 25 mg (all P < 0.0001). By week 20, the cumulative BP threshold of < 140/90 mm Hg was achieved by 86.8% and 84.2% of patients aged ≥ 65 and < 65 years, respectively. Among patients aged ≥ 65 years who underwent ambulatory BP monitoring, mean 24-hour, daytime, and nighttime ambulatory BP all decreased from baseline at weeks 12 and 20 (all P < 0.0001). At weeks 12 and 20, the mean 24-hour American Heart Association-recommended ambulatory BP target of < 130/80 mm Hg was achieved in 80.4% and 97.4% of patients aged ≥ 65 years, respectively, and in 71.3% and 88.8% of patients aged < 65 years, respectively. The majority of adverse events were mild to moderate in intensity and the incidence of treatment-emergent adverse events determined by clinical laboratory evaluation was low. The incidence of drug-related hypotension and orthostatic hypotension in patients aged ≥ 65 years was 2.2% and 0.0%, respectively, and in patients aged < 65 years, was 2.3% and 0.3%, respectively. Fixed-dose AML/OM ± HCTZ combination therapy effectively lowered BP and achieved BP goals in patients aged ≥ 65 and < 65 years with hypertension previously uncontrolled on monotherapy. The treatment regimen was well tolerated irrespective of patient age.

Safety and effectiveness of a fixed-dose combination of olmesartan, amlodipine, and hydrochlorothiazide in clinical practice

“…Results from this study indicate that the rate of ADRs was only slightly increased among patients who were over 65 years of age, and those with high cardiovascular risk. A study by Weir et al 18 of an FDC tablet of olmesartan/amlodipine with separate-pill HCT also indicated that age did not have a relevant influence on the ADR rate. Drug-related hypotension and orthostatic hypotension, however, occurred less frequently in patients aged greater than 65 years (2.2% and 0.0%) compared with under 65 years (2.3% and 0.3%).…”

Efficacy and safety of olmesartan medoxomil‑amlodipine besylate tablets (Sevikar®) in older patients with essential hypertension: Subgroup analysis from the Sevikar study

“…OM-AML tablets are an effective antihypertensive agent not only for the general population, but also for older patients, and patients with diabetes mellitus or obesity ( 22 , 23 ). Regarding the effect of OM-AML tablets on older patients with essential hypertension, a previous study demonstrated that the mean change of SeSBP/SeDBP was -14.5/-7.8 mmHg in older patients with uncontrolled hypertension who had previously received monotherapy followed by administration of OM-AML tablets for 20 weeks ( 24 ). Another study showed that after treatment with OM-AML tablets for 36 months, SeSBP/SeDBP decreased from 157.2/84.6 to 132.6/72.6 mmHg in older patients with hypertension ( 25 ), resulting in a mean change of -24.6/-12.0 mmHg for SeSBP/SeDBP.…”

A thorough QTc study demonstrates that olmesartan medoxomil does not prolong the QTc interval

“…The safety of OM for the treatment of hypertension, both as monotherapy and as part of combination therapy, has been demonstrated across multiple patient subgroups in numerous hypertension studies. [7][8][9][10][11][12][13][14][15][16][17] Importantly, the findings of increased rates of cardiovascular death in OM-treated patients in ROADMAP and ORIENT are not supported by more recent large-scale retrospective cohort analyses, which observed no difference in risk between patients initiating OM and those initiating other ARBs or angiotensin-converting enzyme inhibitors. [18][19][20][21] Some concern for increased risk was raised with the use of high-dose olmesartan for �6 months' duration in elderly patients with type 2 diabetes.…”