Greathouse Treatment Irbesartan/HCTZ Olmesartan medoxomil/HCTZ Telmisartan/HCTZ Valsartan/HCTZ Dosage (mg/day) 100/12.5c 300/25 20/12.5 20/25d 40/25e 40/12.5 80/12.5 80/12.5 160/25 Table 1 Antihypertensive efficacy of angiotensin II receptor blocker/HCTZ combination therapies based on indirect comparison of factorial studies of 8 weeks’ duration in hypertensive patients with a DBP of 95–115 mmHg. Results are shown for the starting and the maximum approved dosages in the United States and Europe for each combination therapy (Benz et al 1998; McGill and Reilly 2001; Chrysant et al 2004; Ram 2004) Mean absolute (placebo-subtracted) reduction from baseline (mmHg)a SBP 14.9 (12.6) 23.1 (20.8) 20.1 (16.8) 27.1 (23.8) 26.8 (23.5) 18.8 (15.9) 23.9 (21.0) 16.5 (14.6) 22.4 (20.5) DBP 11.9 (8.4) 14.4 (10.9) 16.4 (8.2) 20.0 (11.8) 21.9 (13.7) 12.6 (8.8) 14.9 (11.1) 11.8 (7.7) 15.3 (11.2) Absolute (placebo- subtracted) response rateb (%) – – 79 (41) 89 (51) 92 (54) 63 (34) 79 (50) 64 (35) 81 (52) aMean change in SBP and DBP at study end (or last observation carried forward) in the intent-to-treat population, except for the irbesartan study for which data are for those completing the study and/or having a week 8 BP reading. Seated BP, except for the telmisartan study which reported supine readings. bResponse defined as DBP <90 mmHg or a decrease from baseline of ≥10 mmHg. cMarketed combination is 150/12.5 mg. dMaximum in Europe. eMaximum in United States. Abbreviations: BP, blood pressure; DBP, diastolic BP; HCTZ, hydrochlorothiazide; SBP, systolic BP. between amlodipine besylate/benazepril and olmesartan medoxomil/HCTZ has not been performed; however, an indirect comparison of data from several factorial studies (Quan et al 2006) suggests that mean reductions in seated DBP may be quantitatively greater with olmesartan medoxomil/HCTZ 40/25 mg/day than with amlodipine besylate/benazepril 5/20 mg/day (approximately 22 vs 17 mmHg), whereas reductions in seated SBP appear similar between the combinations (approximately 27 vs 27 mmHg) (Quan et al 2006). The studies used similar designs and enrolled patients with a baseline DBP of 100–115 mmHg. However, a head-to-head trial is needed to properly compare these combination therapies, and inclusion of the highest available dosage of amlodipine besylate/benazepril 10/ 20 mg (for which factorial study data were not available) would be of interest. Tolerability of olmesartan medoxomil/HCTZ Looking first at the individual components, an integrated analysis of efficacy and safety demonstrated that the adverse events profile observed with olmesartan medoxomil monotherapy is similar to that seen with placebo, with dizziness the only adverse event to occur in a significantly greater number of olmesartan medoxomil patients compared with placebo (2.8% vs 0.9%, respectively, p=0.01) (Neutel 406 2001). In comparison, HCTZ has been associated with metabolic disturbances and electrolyte imbalances, including hypokalemia and hyponatremia, particularly at higher doses (Sweetman 2005). Physiological processes that conserve sodium in the body, such as activation of the RAS, produce an augmentation of renal potassium excretion (Reyes 2002). Although clinical data are still lacking, it has been suggested that the inhibition of the RAS resulting from co-therapy with an ARB may reduce potassium loss, making hypokalemia less of a potential problem among patients receiving this combination (Kjeldsen et al 2005). In addition, the tendency of HCTZ to elevate blood glucose levels and promote type 2 diabetes mellitus may be offset with the use of ARBs which have been shown to reduce the incidence of new-onset diabetes as compared with β-blocker/HCTZ therapy (Dahlof et al 2002). Adverse events associated with the combination of olmesartan medoxomil plus HCTZ are generally mild-to- moderate in severity (Ball et al 2001; Chrysant et al 2004; Neutel et al 2004; Rump et al 2006). Dizziness was reported by more olmesartan medoxomil/HCTZ recipients than placebo recipients in placebo-controlled trials, and was associated with the addition of HCTZ (incidence 9% for olmesartan medoxomil/HCTZ vs 2% for placebo vs 8% for HCTZ monotherapy and 1% for olmesartan medoxomil monotherapy) (Daiichi Sankyo, Inc. 2005). Upper Vascular Health and Risk Management 2006:2(4)