P-158: Efficacy of olmesartan medoxomil (O) and O/hydrochlorothiazide (H) in achieving blood pressure (BP) control and normalization in stage 2 systolic hypertension (HTN)

Abstract

The JNC 7 report stresses the importance of reducing systolic BP (SBP) and states that ≥2 agents are usually required to achieve goal BP (<160 mmHg) in Stage 2 systolic HTN. This study evaluated the efficacy of an open label titration regimen using the angiotensin receptor blocker O alone and in combination with H to achieve goal BP (<140/90 mmHg) and to normalize BP (<120/80 mmHg) in Stage 2 systolic HTN. After a placebo run-in, 169 patients (pts) with seated SBP ≥160 and <200 mmHg and diastolic BP (DBP) <110 mmHg received O 20 mg/d for 3 wks. Uptitration occurred at 3-wk intervals if BP remained ≥120/80 mmHg according to the schedule: O 40 mg/d, combination with H 12.5 mg/d, then H 25 mg/d. If BP remained ≥120/80 mmHg, pts could enter a 4-wk extension phase, with H increased to 50 mg/d. The primary endpoint was change from baseline in mean trough SBP at 12 wks. Secondary endpoints included BP changes from baseline at the end of each titration period and the percentage of pts achieving BP <140/90 and <120/80 mmHg. Mean age was 60 yrs, 46% of pts were male and 84% were non-black; mean baseline BP was 171/95 mmHg. Marked reductions in BP were seen at the end of each titration step (Table; P<0.001 compared with baseline for SBP and DBP at all times analyzed). At wk 12, with the highest approved dose (O/H 40/25 mg/d), a mean reduction in SBP of -34.7 mmHg allowed 70% of pts to achieve goal BP <140/90 mmHg and 15% to achieve normal BP (<120/80 mmHg). Increasing H to 50 mg/d allowed further reductions in SBP, which led to 78% of pts achieving goal BP and 27% achieving normal BP. In conclusion, O monotherapy is effective in reducing SBP and, combined with H, provides additional BP reduction, resulting in a substantial proportion of pts achieving BP goal and normalization.

Week	3	6	9	12	16(Extension)
Treatment step	O 20	O 40	O 40 + H 12.5	O 40 + H 25	O 40 + H 50
n	169	160	157	144	106
Mean ΔSBP (mmHg)	−16.9	−18.4	−30.3	−34.7	−38.3
SBP <140 mmHg (%)	17.8	30.8	58.0	75.1	81.1
SBP/DBP <140/90 mmHg (%)	15.4	29.0	55.6	70.4	77.5
SBP <120 mmHg (%)	1.2	1.2	6.5	16.0	27.8
SBP/DBP <120/80 mmHg (%)	1.2	1.2	5.9	15.4	27.2

Olmesartan, Olmesartan/HCTZ Combination Therapy, Stage 2 Systolic Hypertension