P-243: A comparative analysis of the efficacy of olmesartan medoxomil (O)/hydrochlorothiazide (HCTZ), valsartan (V)/HCTZ, irbesartan (I)/HCTZ and telmisartan (T)/HCTZ combinations

Abstract

Most hypertensive patients require more than one drug for adequate blood pressure (BP) control. JNC 7 recommends starting therapy with a thiazide diuretic and adding a drug from a different class if BP is >20/10 mm Hg. Considering the paucity of head-to-head studies, the aim of this review is to compare the efficacy of angiotensin receptor blocker (ARB)/HCTZ combinations in similarly designed placebo-controlled, factorial studies. The comparison was limited to published, fixed-dose combination studies. Medline, EMBASE, and BIOSYS searches identified 3 published multicenter, randomized, double-blind, fixed-dose, placebo-controlled, factorial-design studies with V/HCTZ, I/HCTZ, and T/HCTZ to compare to O/HCTZ (Chrysant et al. Am J Hypertens. In press). The demographic and baseline characteristics of the study populations were similar. The mean age across all studies was 52 to 55 years and the percentage of male patients ranged from 56–65%. The primary efficacy endpoint was decrease from baseline in mean DBP after 8 weeks of therapy. Other endpoints included BP response rate and decrease in mean SBP. The results presented represent data with the low- and high-dose formulations of the marketed doses of each drug (Table). O/HCTZ 40/25mg reduced SBP/DBP by 26.8/21.9 mm Hg compared to 22.5/15.3, 15.9/15.0, and 23.9/14.9 mm Hg for V/HCTZ 160/25mg, I/HCTZ 300/12.5mg, and T/HCTZ 80/12.5mg, respectively. Similarly, the lowest marketed doses reduced SBP/DBP by 20.9/15.5, 16.5/11.8, 14.9/11.9, and 18.8/12.6 mm Hg for O/HCTZ 20/12.5mg, V/HCTZ 80/12.5mg, I/HCTZ 100/12.5mg,^a and T/HCTZ 40/12.5mg, respectively. All combinations were well tolerated, with an incidence of adverse events similar to ARB monotherapy. Additional head-to-head clinical trials should be done to confirm these observations.

ARB/HCTZ Combination	No. of Subjects	SBP/DBP Reductions in mm Hg (responder rate %)
Olmesartan medoxomil
PBO	42	3.4/7.7 (38)
20/12.5	44	20.9/15.5 (79)
40/25	39	26.8/21.9 (92)
Valsartan
PBO	94	1.9/4.1 (29)
80/12.5	96	16.5/11.8 (64)
160/25	94	22.5/15.3 (81)
Irbesartan
PBO	38	2.3/3.5 (24)
100/12.5a	38	14.9/11.9 (NA)
300/12.5	43	15.9/15.0 (NA)
Telmisartan
PBO	73	2.9/3.8 (29)
40/12.5	70	18.8/12.6 (63)
80/12.5	73	23.9/14.9 (79)

Responder rate trough DBPlt;90 mm Hg and/or ≥ 10 mm Hg decrease from baseline.

a

Dose tested was 100/12.5mg although marketed dose is 150/12.5mg.

Olmesartan, ARB/HCTZ, Combination Therapy