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.

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

objectiveThe 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).

methodsFollowing 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.

resultsBaseline 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.

conclusionsIn 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.