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

Background: The incidence of hypertension, particularly isolated systolic hypertension, increases with increasing 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 I 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 <140/90 mmHg (stage I 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 <140/90 mmHg 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.