respiratory tract infections were also more frequent with olmesartan medoxomil/HCTZ than with placebo (7% vs 0%) (Daiichi Sankyo, Inc. 2005). Discussion Although it is generally recommended that antihypertensive therapy be initiated with a single agent, it is recognized that most patients will eventually require combination therapy to achieve recommended BP goals (Chobanian et al 2003; European Society of Hypertension 2003; Whitworth 2003). Indeed, JNC 7 suggests that in patients with Stage 2 hypertension (SBP ≥160 mmHg or DBP ≥100 mmHg), treatment should be initiated with two antihypertensive agents (Chobanian et al 2003; European Society of Hypertension 2003). Combination therapy typically consists of drugs from different classes with complementary mechanisms of action, such as a thiazide diuretic plus an agent that acts on the RAS (European Society of Hypertension 2003; Chobanian et al 2003). Olmesartan medoxomil/HCTZ is one such combination, and is available as fixed-dose, once-daily preparations indicated for the treatment of hypertension, although not indicated for first-line therapy. In clinical trials, olmesartan medoxomil/HCTZ has demonstrated greater antihypertensive efficacy than either component as monotherapy (Chrysant et al 2004; Sellin et al 2005) and appears to compare favorably with other ARB/HCTZ combinations (Conlin et al 2000; McGill and Reilly 2001; Sachse et al 2002; Ram 2004; Lacourciere et al 2005; Neutel et al 2005; Rump et al 2006) and other fixed-dose combinations from different antihypertensive drug classes (Ball et al 2001; Quan et al 2006). However, limited head- Olmesartan medoxomil/hydrochlorothiazide in hypertension to-head trials suggest the need for additional comparative trials in order to determine adequately potential differences in the BP-lowering effects and BP goal attainment rates achievable with these combination products. It is well known that hypertension outcomes can be improved in clinical practice by setting target BP goals and providing physicians with easy-to-follow treatment algorithms (Singer et al 2002; Neutel et al 2004). A target level of <140/90 mmHg is recommended for patients with uncomplicated hypertension and no evidence of diabetes or renal disease (Chobanian et al 2003; European Society of Hypertension 2003; Whitworth 2003). Importantly, in an open-label trial, 9 out of 10 patients with Stage 1 hypertension, and more than half of patients with Stage 2 hypertension achieved an aggressive BP goal of ≤130/ 85 mmHg when treated with olmesartan medoxomil/HCTZ (Neutel et al 2006). It is known that systolic hypertension is a better predictor of future cardiovascular morbidity than diastolic hypertension, especially in older patients (Izzo et al 2000; European Society of Hypertension 2003). However, SBP is often more difficult to control than DBP (Swales 1999; Mancia et al 2002). Treatment algorithms based on olmesartan medoxomil/HCTZ have been shown to significantly reduce SBP, in addition to DBP, in patients with Stage 1 and Stage 2 hypertension, allowing the majority of patients in both groups to achieve the SBP goal of ≤140 mmHg (Neutel et al 2006). Various factors affect compliance and persistency with antihypertensive treatment. Long-term compliance has been shown to be better if initial therapy is well tolerated and the efficacy response is reasonably good (Caro et al 1999). Table 2 Antihypertensive efficacy of other angiotensin II receptor blocker/HCTZ combinations based on indirect comparison through a meta-analysis of randomized, double-blind, controlled trials assessing cuff BP in hypertensive patients with a DBP of 95– 115 mmHg. Results are shown for starting dosages in the United States or Europe for each combination (Conlin et al 2000). For indirect comparative purposes, data for the starting dosage of olmesartan medoxomil/HCTZ from a randomized, double-blind, controlled trial in patients with Stage 1 or Stage 2 hypertension are also tabulated (Chrysant et al 2004; Rump et al 2006) Treatment Dosage Mean absolute reduction from Absolute response rateb (mg/day) baseline (mmHg)a (%) Candesartan/HCTZ Irbesartan/HCTZ Losartan/HCTZ Valsartan/HCTZ Olmesartan medoxomil/HCTZc 8/12.5 150/12.5 50/12.5 80/12.5 20/12.5 aWeighted average change in cuff SBP and DBP for the meta-analysis. bResponse defined as DBP <90 mmHg or a decrease from baseline of ≥10 mmHg. cResults from a trial with olmesartan medoxomil/HCTZ that was not part of the meta-analysis. Abbreviations: DBP, diastolic BP; HCTZ, hydrochlorothiazide; SBP, systolic BP. Vascular Health and Risk Management 2006:2(4) SBP 20.6 16.1 16.5 19.7 20.1 DBP 9.9 12.4 12.0 13.6 16.4 56 66 70 66 79 407