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Blood Pressure-Lowering Efficacy of an Olmesartan Medoxomil/Hydrochlorothiazide-Based Treatment Algorithm in Elderly Patients (Age ≥65 Years) Stratified by Age, Sex and Race

Subgroup Analysis of a 12-Week, Open-Label, Single-Arm, Dose-Titration Study

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Abstract

Introduction: Hypertension is a leading risk factor for development of heart failure, stroke and renal disease in the elderly.

Objective: The objective of this study was to evaluate, by means of a prespecified secondary analysis of a 12-week, open-label, single-arm, dose-titration study, the blood pressure (BP)-lowering efficacy and safety of an olmesartan medoxomil (OM)/hydrochlorothiazide (HCTZ)-based titration regimen in patients aged ≥65 years with hypertension. Subgroups were stratified by age (≥65 to ≤75 or >75 years), sex (male or female) and race (Black or non-Black).

Methods: Following a 2- to 3-week placebo run-in phase, patients received OM 20 mg, uptitrated to OM 40 mg, followed by addition of HCTZ 12.5–25 mg step-wise at 3-week intervals if seated cuff BP (SeBP) was ≥ 120/70 mmHg. Patients below this target SeBP were maintained at their current dose but uptitrated to the next consecutive dose if mean seated cuff systolic BP (SBP) was ≥140 mmHg and/or mean seated cuff diastolic BP was ≥90 mmHg at follow-up visits. Efficacy was assessed by 24-hour ambulatory BP monitoring (ABPM) and SeBP measurements. The primary efficacy variable was the change from baseline in mean 24-hour ambulatory SBP after 12 weeks. Secondary efficacy endpoints included the change from baseline in mean 24-hour ambulatory SBP; change from baseline in ambulatory BP during the daytime (8:00 am–4:00 pm), nighttime (10:00 pm–6:00 am) and the last 6, 4 and 2 hours of the dosing interval; change from baseline in SeBP at each titration step and at study end; and the proportion of patients achieving mean 24-hour ambulatory BP targets and SeBP goals at week 12. The frequency and severity of treatment-emergent adverse events (TEAEs) were also documented.

Results: Baseline and week 12 ABPM data were available for 150 out of 178 patients who entered the active treatment phase. Changes from baseline in mean 24-hour ambulatory BP were −26.0/−12.5 mmHg and −24.9/−12.0 mmHg in patients aged ≥65 to ≤75 years (n = 128) and >75 years (n = 48), respectively (all p < 0.0001 vs baseline). Changes from baseline in mean 24-hour ambulatory BP were −26.0/−13.0 mmHg and −25.4/−11.5 mmHg in male (n = 92) and female (n = 84) patients, respectively (all p < 0.0001 vs baseline) and −26.7/−11.8 mmHg and −25.6/−12.4 mmHg in Black (n = 28) and non-Black (n = 148) patients, respectively (all p < 0.0001 vs baseline). Clinically significant ambulatory BP reductions were observed during the daytime, nighttime and the last 6, 4 and 2 hours of the dosing interval in all subgroups. Changes from baseline at week 12 in mean SeBP were similar to 24-hour ambulatory BP changes reported previously. At week 12, the proportion of patients achieving the 24-hour ambulatory BP target of <30/80 mmHg ranged from 67.5% to 77.4% and achieving the SeBP goal of <140/90mmHg ranged from 60.7% to 68.8% across the subgroups. Most TEAEs and drug-related TEAEs were mild or moderate in severity, and there were no trends across subgroups.

Conclusions: In a subgroup analysis based upon age, sex and race in patients aged ≥65 years with hypertension, an OM/HCTZ-based algorithm was efficacious and well tolerated.

ClinicalTrials.gov Identifier: NCT00412932

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Acknowledgements

This study was supported by Daiichi Sankyo, Inc. We thank Christopher J. Jones, PhD, and Alan J. Klopp, PhD, of inScience Communications, a Wolters Kluwer business, for providing medical writing support, which was funded by Daiichi Sankyo, Inc.

Joel Neutel is a member of the Speaker’s Bureau for Novartis, Boehringer Ingelheim, Daiichi Sankyo, Inc., The Bristol-Myers Squibb/Sanofi Pharmaceutical Partnership, Forest Pharmaceuticals and Pfizer Inc. Dean J. Kereiakes is employed by The Christ Hospital, of which The Carl and Edyth Lindner Center for Research and Education is a wholly owned subsidiary. The Lindner Center has received significant research support from Daiichi Sankyo, Inc. Dr Kereiakes is a member of the Speaker’s Bureau for Eli Lilly & Co., has received consultancy fees from Devax, Eli Lilly & Co., Boston Scientific, Abbott Vascular, Medpace and REVA Medical Inc., and has received grant and/or research support from Abbott Vascular, Amylin Pharmaceuticals, Boston Scientific and Daiichi Sankyo, Inc. Kathy A. Stoakes, Jen-Fue Maa and Ali Shojaee are all employees of Daiichi Sankyo, Inc. At the time of writing, William F. Waverczak was an employee of Daiichi Sankyo, Inc.

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Neutel, J., Kereiakes, D.J., Stoakes, K.A. et al. Blood Pressure-Lowering Efficacy of an Olmesartan Medoxomil/Hydrochlorothiazide-Based Treatment Algorithm in Elderly Patients (Age ≥65 Years) Stratified by Age, Sex and Race. Drugs Aging 28, 477–490 (2011). https://doi.org/10.2165/11589460-000000000-00000

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