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.

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 178patients 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 <130/80 mmHg ranged from 67.5% to 77.4% and achieving the SeBP goal of <140/90 mmHg 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.