(10, 20, or 40 mg/day), HCTZ monotherapy (12.5 or 25 mg/ day), one of six groups of olmesartan medoxomil/HCTZ combination therapy (covering each possible dosage combination), or placebo. A dose-dependent decrease in BP was seen across all olmesartan medoxomil/HCTZ combinations compared with the individual components, with the maximum mean reduction of 26.8/21.9 mmHg observed with the highest- dose combination, olmesartan medoxomil/HCTZ 40/25 mg/ day. After 8 weeks, mean reductions in seated DBP were 13.5–21.9 mmHg with combination therapy, compared with 11.3–14.6 mmHg with olmesartan medoxomil monotherapy (10–40 mg/day), and 10.2–12.9 mmHg with HCTZ monotherapy (12.5 or 25 mg/day). All combination and monotherapy regimens reduced DBP and SBP significantly more than placebo (Chrysant et al 2004). The proportion of patients achieving a BP response (defined as trough seated DBP <90 mmHg or a decrease from baseline of ≥10 mmHg) increased in a dose-dependent manner with each monotherapy and with combination therapy, although between-group statistical comparisons were not performed (Chrysant et al 2004). The response rate was 92.3% for olmesartan medoxomil/HCTZ 40/25 mg/ day; diastolic control (trough seated DBP <90 mmHg) and systolic control (trough seated SBP <140 mmHg) were achieved in 79.5% and 87.2% of patients, respectively (Chrysant et al 2004). Additional support for combination therapy with olmesartan medoxomil/HCTZ comes from a trial in hypertensive patients with a seated DBP of 100–115 mmHg, a seated SBP >150 mmHg, a 24-hour DBP ≥84 mmHg, and at least 30% DBP daytime readings >90 mmHg. Mean seated DBP remained ≥90 mmHg after 4 weeks of treatment with olmesartan medoxomil 20 mg/day; however, the addition of HCTZ 12.5 or 25 mg for 8 weeks significantly reduced mean 24-hour DBP (–1.9 mmHg for HCTZ 12.5 mg, p=0.0167; –3.7 mmHg for HCTZ 25 mg, p<0.0001) and SBP (–3.8 mmHg for HCTZ 12.5 mg, p=0.0018; –7.4 mmHg for HCTZ 25 mg, p<0.0001) compared with the addition of placebo (Sellin et al 2005). Evaluation of treatment algorithm including olmesartan medoxomil/HCTZ A stepwise treatment algorithm in which uptitration of olmesartan medoxomil is followed by the addition of increasing dosages of HCTZ is an effective option in patients with Stage 1 or Stage 2 hypertension (Neutel et al 2004, 2006). Vascular Health and Risk Management 2006:2(4) Olmesartan medoxomil/hydrochlorothiazide in hypertension In this open-label, multicenter study (n=210), olmesartan medoxomil 20 mg/day was initially administered for 4 weeks. Antihypertensive drug treatment was then uptitrated at 4-week intervals until goal BP was achieved, progressing through the following steps: uptitration to olmesartan medoxomil 40 mg/day, addition of HCTZ 12.5 mg/day, uptitration of HCTZ to 25 mg/day, addition of amlodipine besylate 5 mg/day, and then uptitration of amlodipine besylate to 10 mg/day (Neutel et al 2004, 2006). Endpoints included the percentage of patients who achieved the BP goal of ≤140/90 mmHg, and the more aggressive BP goal of ≤130/85 mmHg. Those patients who achieved the more aggressive BP goal at any time during the study exited the trial. The results of this study showed that a BP goal of ≤140/ 90 mmHg and a more aggressive BP goal of ≤130/85 mmHg could be achieved in many patients using a combination of olmesartan medoxomil and HCTZ (Neutel et al 2004, 2006). The goal of ≤140/90 mmHg was achieved in 83% of patients after 8 weeks of dual combination therapy with olmesartan medoxomil/HCTZ (titrated to 40/25 mg/day), while the goal of ≤130/85 mmHg was attained in 69% (Neutel et al 2004). Mean BP reductions and goal attainment rates for all patients and for patients separated into those with Stage 1 or Stage 2 hypertension are shown in Figure 1. Looking specifically at the SBP goal (≤140 mmHg), 96.2% of patients with Stage 1 hypertension (mean baseline SBP of 151.1 mmHg) and 78% of those with Stage 2 hypertension (mean baseline SBP 169.8 mmHg) achieved this goal (Neutel et al 2006). For all patients combined after 8 weeks of treatment with olmesartan medoxomil/HCTZ (titrated to 40/25 mg/day), mean BP had decreased from baseline by 29.3/16.1 mmHg, representing an incremental mean BP reduction of approximately 11.6/5.4 mmHg beyond that achieved with monotherapy. The addition of amlodipine besylate led to further decreases in BP (Neutel et al 2004). Comparison with other ARB/HCTZ combinations One direct comparison of olmesartan medoxomil/HCTZ with another ARB/HCTZ combination has been published recently. In this starting-dose, open-label comparison, olmesartan medoxomil/HCTZ and losartan/HCTZ were compared as initial therapy in patients with either newly diagnosed Stage 2 hypertension or a DBP of 90–100 mmHg despite treatment (Rump et al 2006). In this randomized, double-blind, multicenter trial, patients were treated with 403