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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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Authors and Affiliations

  1. Orange County Research Center, 14351 Myford Road, Tustin, California, 92780, USA

    Joel Neutel (Medical Director of Clinical Pharmacology)

  2. The Christ Hospital Heart and Vascular Center and The Carl and Edyth Lindner Center for Research and Education at The Christ Hospital, Cincinnati, Ohio, USA

    Dean J. Kereiakes

  3. Daiichi Sankyo, Inc., Parsippany, New Jersey, USA

    Kathy A. Stoakes, Jen-Fue Maa, Ali Shojaee & William F. Waverczak

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  1. Joel Neutel
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Correspondence to Joel Neutel.

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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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