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Efficacy of Olmesartan Medoxomil and Hydrochlorothiazide Fixed-Dose Combination Therapy in Patients Aged 65 Years and Older with Stage 1 and 2 Hypertension or Isolated Systolic Hypertension

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Abstract

Background: The incidence of hypertension, particularly isolated systolic hypertension, increases with in-creasing age, as does the risk of fatal cardiovascular disease. A combination antihypertensive therapy regimen may be required to reach recommended BP goals in older patients.

Objectives: This study set out to report blood pressure (BP) data in elderly patients across the subgroups of stage 1 and stage 2 hypertension (prespecified subgroup) and isolated systolic hypertension (ISH) [post hoc]. Design and Setting: This was a subgroup analysis of a prospective, open-label study carried out in a multicenter, outpatient setting (e.g. the BeniSILVER [Benicar Efficacy: New Investigation Shows OM Treatment Increasingly Leads to Various Elderly Populations to Safe BP Reductions; ClinicalTrials.gov identifier: NCT00412932] study). The study included 176 patients with a mean age of approximately 72 years; stage 1 hypertension, 60, stage 2 hypertension, 116, and ISH, 98.

Intervention: After a 2- to 3-week placebo run-in period, patients were uptitrated every 3 weeks from olmesartan medoxomil (OM) 20 mg daily to OM 40 mg, OM/hydrochlorothiazide (HCTZ) 40 mg/12.5 mg, and OM/HCTZ 40 mg/25 mg, if seated cuff BP (SeBP) was ≥120/70 mmHg.

Measurements: Measurements included change from baseline in mean 24-hour ambulatory BP and SeBP after 12 weeks of treatment, percentage of patients achieving a cumulative SeBP goal of <140/90mmHg (stage 1 and stage 2 cohorts) or seated cuff systolic BP (SeSBP) goal of <140 mmHg (ISH cohort), and the incidence of adverse events (AEs).

Results: Combination therapy was required by 159 patients. Changes from baseline in mean 24-hour ambulatory BP (±standard deviation [SD]) were −24.2 (± 11.8)/−11.8 (± 6.9) mmHg, −26.5 (± 11.8)/−12.6 (± 6.7) mmHg, and −24.7 (− 12.5)/−11.2 (± 6.4) mmHg in the stage 1, stage 2, and ISH cohorts, respectively (all p< 0.001 vs baseline). Mean SeBP changes (± SD) from baseline in patients titrated to OM/HCTZ 40 mg/25 mg were −24.6 (± 11.4)/−10.5 (± 7.3) mmHg in the stage 1 cohort, −26.4 (± 17.2)/−11.3 (±9.7) mmHg in the stage 2 cohort, and −21.5 (± 15.6)/−6.8 (± 7.8) mmHg in the ISH cohort (all p <0.001). The cumulative proportions of patients achieving an SeBP goal of <140/90mmHg by week 12 were 88.3%, 56.0%, and 72.4% in the stage 1, stage 2, and ISH cohorts, respectively, while 72.4% of patients achieved an SeSBP of <140 mmHg in the ISH cohort. Treatment-emergent AEs ranged from 32.3% to 32.8%, with <3% of patients reporting drug-related hypotension.

Conclusion: An OM/HCTZ-based titration regimen enabled elderly patients with hypertension to safely reduce BP throughout the 24-hour dosing interval and allowed the majority of these patients to achieve a BP target of <140/90 mmHg or <140 mmHg.

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Acknowledgments

Medical writing services and editorial assistance provided by Claire Pouwels, Robert Schupp, PharmD, and Alan J. Klopp, PhD, of inScience Communications, Springer Healthcare, were funded by Daiichi Sankyo, Inc.

Role of the Funding Source

Daiichi Sankyo, the study sponsor, was involved in the study concept and design, acquisition of subjects/data (oversight of the CRO), analysis and interpretation of data, and preparation of the manuscript.

Conflict of Interest Statements

F. Wilford Germino, MD, has received research grants from Daiichi Sankyo, Inc., Novartis, and Sanofi, and honoraria from Bristol-Myers Squibb, AstraZeneca, Forest Laboratories, Takeda, and Pfizer.

Joel Neutel, MD, is a member of the speaker’s bureau for Novartis, Boehringer Ingelheim, Daiichi Sankyo, Inc., the Bristol-Myers Squibb/Sanofi Pharmaceutical Partnership, Takeda, and Pfizer Inc.

Robert Dubiel, PharmD, is a stockholder and a former employee of Daiichi Sankyo, Inc.

Jen-Fue Maa, PhD, and Kathleen J. Chavanu, PharmD, are both employees of Daiichi Sankyo, Inc.

Author Contributions

F. Wilford Germino, MD, and Joel M. Neutel, MD, were involved as investigators with recruitment of patients as well as their ongoing care. They did not interpret data directly, but were involved in the review of the data. Both participated in the preparation of the manuscript with involvement from inception throughout the writing process, with editing and revisions.

Robert Dubiel, PharmD, participated in the study concept and design, interpretation of data, and manuscript review and comment.

Jen-Fue Maa, PhD, was involved in study design, data analysis, interpretation of data, and preparation of the manuscript.

Kathleen J. Chavanu, PharmD, was involved in the analysis and interpretation of data and preparation of the manuscript.

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Authors and Affiliations

  1. Department of Internal Medicine, Orland Primary Care Specialists, 16660 S 107th Avenue, Orland Park, Illinois, IL 60467, USA

    F. Wilford Germino

  2. Orange County Research Center, Tustin, California, USA

    Joel M. Neutel

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

    Robert Dubiel, Jen-Fue Maa & Kathleen J. Chavanu

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  1. F. Wilford Germino
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  2. Joel M. Neutel
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Correspondence to F. Wilford Germino.

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Germino, F.W., Neutel, J.M., Dubiel, R. et al. Efficacy of Olmesartan Medoxomil and Hydrochlorothiazide Fixed-Dose Combination Therapy in Patients Aged 65 Years and Older with Stage 1 and 2 Hypertension or Isolated Systolic Hypertension. Am J Cardiovasc Drugs 12, 325–333 (2012). https://doi.org/10.1007/BF03261841

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