For indirect comparative purposes, data from a meta- analysis (Conlin et al 2000) evaluating randomized controlled trial data of several other ARB/HCTZ combinations are presented in Table 2. All trials were in hypertensive patients with a DBP of 95–115 mmHg, assessed cuff BP, and used a similar definition of response rates (DBP <90 mmHg or a decrease from baseline of ≥10 mmHg). Combination therapy with HCTZ 12.5 mg/day plus starting doses of candesartan, irbesartan, losartan, or valsartan was associated with mean reductions in BP of 16.1–20.6/9.9– 13.6 mmHg and response rates of 56–70% when administered at starting combination doses. In a trial of eprosartan/HCTZ 600/12.5 mg/day which used similar criteria as above, mean BP reductions of 9.2/10.7 mmHg and a response rate (DBP<90 mmHg or within 90– 100 mmHg with a decrease of ≥10 mmHg) of 73% were reported (Sachse et al 2002). Based on these indirect comparisons, olmesartan medoxomil/HCTZ may achieve BP response rates that compare favorably with other ARB/ HCTZ combinations at starting dosages (Table 2). However, SBP DBP a b )g 0 Hm -5 (m-10 P iengB--1250 n ach-25 an-30 e M-35 )(%50 P45 lB40 ao35 gg30 ivn25 ie20 h ca15 ts10 ien 5 ta 0 P -29.3 -24.9 43.2 -17.6 -16.5 OLM/HCTZ LOS/HCTZ 32.1 OLM/HCTZ LOS/HCTZ Figure 2 Antihypertensive efficacy of olmesartan medoxomil/HCTZ 20/12.5 mg/ day (n=308) compared with losartan/HCTZ 50/12.5 mg/day (n=305) as initial therapy in patients with moderate to severe hypertension. Results of a randomized, double-blind trial of 12 weeks’ treatment in 613 patients who had either newly diagnosed hypertension with mean seated DBP 100–120 mmHg and SBP ≥160 mmHg or inadequately controlled hypertension with DBP 90– 110 mmHg despite previous treatment (Rump et al 2006). (a) Reduction in mean trough BP (DBP = primary endpoint); (b) Proportion of patients achieving BP control (<140/90 mmHg) are shown for the intent-to-treat population. *p=0.002, **p≤0.0003. Abbreviations: DBP, diastolic BP; HCTZ, hydrochlorothiazide; LOS, losartan; OLM, olmesartan medoxomil; SBP, systolic BP. Vascular Health and Risk Management 2006:2(4) Olmesartan medoxomil/hydrochlorothiazide in hypertension direct comparative studies are required to confirm these findings. Lastly, a study evaluating irbesartan/HCTZ in patients with Stage 1 systolic hypertension (SBP 140–159 mmHg) uncontrolled by monotherapy found that treatment with irbesartan/HCTZ 300/25 mg/day led to a mean reduction in BP of approximately 21.5/10.4 mmHg (from a mean baseline BP of 154/91 mmHg), with 69% of patients reaching the combined BP goal of <140/90 mmHg, and 77% achieving SBP goal, after 18 weeks (Neutel et al 2005). In comparison, in a trial discussed earlier, olmesartan medoxomil/HCTZ 40/25 mg/day reduced mean BP by 24.8/15.8 mmHg (from a baseline of 151.1/94.7 mmHg) in patients with Stage 1 hypertension, and by 32.7/16.3 mmHg (baseline 169.8/ 98.6 mmHg) in those with Stage 2 hypertension; SBP goal (≤140 mmHg) was achieved in 96.2% and 78% of these subgroups, respectively (Neutel et al 2006). Additional direct comparative studies are now needed to more accurately determine the comparative efficacy of olmesartan medoxomil/HCTZ and other ARB/HCTZ combinations. Comparison with other antihypertensive combinations Several clinical studies have compared the efficacy of olmesartan medoxomil/HCTZ with other antihypertensive combination therapies. For example, a study that compared olmesartan medoxomil/HCTZ with atenolol/HCTZ found that the antihypertensive efficacy of both combinations was statistically comparable (Ball et al 2001). In this double- blind, non-inferiority study, 328 patients with a mean seated DBP of 100–120 mmHg receiving HCTZ 25 mg/day were randomized to receive olmesartan medoxomil 10 mg/day or atenolol 50 mg/day in addition to the HCTZ dose for 12 weeks, with dose-doubling after 4 weeks, if necessary. Reductions in mean seated SBP and DBP (primary endpoint) were 20.4/17.3 mmHg for olmesartan medoxomil/HCTZ and 19.6/17.2 mmHg for atenolol/HCTZ. The upper limit of the one-sided confidence interval (CI) for the between- group difference for change in DBP (–0.08 mmHg; 90% CI –1.17, 1.02) was within the prespecified least squares mean limit of ≤3.5 mmHg, confirming that the efficacy of olmesartan medoxomil/HCTZ was not inferior to atenolol/ HCTZ. The outcome was similar for SBP (between-group difference –0.8 mmHg, 95% CI –2.61, 1.00) (Ball et al 2001). Amlodipine besylate/benazepril is a well-established, fixed-dose calcium channel blocker/ACE inhibitor combination antihypertensive therapy. A direct comparison 405