Impact of angiotensin receptor blockade in combination with hydrochlorothiazide 25 mg in 2121 patients with stage 1–2 hypertension

Abstract

The antihypertensive effects of telmisartan 80 mg versus valsartan 160 mg, both combined with hydrochlorothiazide (HCTZ) 25 mg, were assessed in a pooled analysis from two large trials with identical study designs in patients with stage 1-2 hypertension. The trials were double-blind with a 4:4:1 randomization scheme to compare once-daily telmisartan 80 mg and HCTZ 25 mg versus once-daily valsartan 160 mg and HCTZ 25 mg versus once-daily placebo on reductions in clinic blood pressure (BP). The primary end point was changes from baseline in BP at the end of 8 weeks. In total, 2121 patients were randomized (telmisartan-HCTZ, 942, valsartan-HCTZ, 952, and placebo, 227) and had baseline seated BPs of 154/102 and 155/102 mm Hg in the two studies, respectively. Changes from baseline in BP after administration of telmisartan-HCTZ (À24.5/ À18.0 mm Hg) were significantly greater than for both placebo (À4.1/À6.5 mm Hg) and valsartan-HCTZ (À22.3/ À16.8 mm Hg) (versus placebo, Po0.0001 for systolic and diastolic BP; versus valsartan-HCTZ, P ¼ 0.0004 for systolic BP and P ¼ 0.0019 for diastolic BP). Adverse event rates were higher in the placebo group than in the active treatment groups (placebo, 41%, telmisartan-HCTZ, 30%, and valsartan-HCTZ, 30%, Po0.05). These data confirm that telmisartan-HCTZ at doses of 80/25 mg lowered systolic and diastolic BP to a greater extent than valsartan-HCTZ at doses of 160/25 mg in stage 1-2 hypertension. The magnitude of the BP-lowering effect provides support for the use of angiotensin receptor blockers with higher doses of a thiazide diuretic (25 mg) to improve hypertension control.

What is a preferred angiotensin II receptor blocker-based combination therapy for blood pressure control in hypertensive patients with diabetic and non-diabetic renal impairment?

“…When a smoothness index was used to evaluate the 24-hour antihypertensive efficacy of several agents, telmisartan 80 mg had a significantly higher smoothness index than the ARBs losartan and valsartan and the ACE inhibitor, ramipril, and was comparable with amlodipine [87]. Telmisartan effectively reduces BP when used alone [32,34,88,89] or in combination with HCTZ [86,90-94] or amlodipine [37,95,96]. Telmisartan/HCTZ has demonstrated superiority over losartan/HCTZ in patients with essential hypertension in terms of 24-hour ambulatory BP, including a BP-lowering effect during the last 6 hours of the dosing interval [92,97,98].…”

“…In the Study of Micardis ® on Obese/Overweight Type-II diabetics with Hypertension (SMOOTH ® ), telmisartan/HCTZ demonstrated significantly greater reductions in mean ambulatory BP over the entire 24-hour dosing interval and during the last 6 hours compared with valsartan/HCTZ [93]. In two large, placebo-controlled trials, telmisartan/HCTZ also demonstrated antihypertensive superiority over valsartan/HCTZ in patients with stages 1 and 2 hypertension [86,94]. …”

A review of the benefits of early treatment initiation with single-pill combinations of telmisartan with amlodipine or hydrochlorothiazide

“…A pooled analysis of the two studies showed that the significant difference in BP reduction in favor of T80/H25 was maintained, regardless of age, sex, or race of the patients 44. In patients with essential hypertension, the T/H SPC was significantly more efficacious than the losartan/HCTZ SPC in reducing BP during the last 6 hours of the dosing interval, as well as in reducing 24-hour ambulatory BP after 6 weeks of treatment 45–47.…”

Effects of Telmisartan with Hydrochlorothiazide versus Valsartan with Hydrochlorothiazide in Patients with Moderate-to-Severe Hypertension

“…Two independent and identically designed trials were previously conducted to evaluate the benefits and safety of two single-pill combination (SPC) therapies: telmisartan 80 mg plus HCTZ 25 mg (T80/H25) and valsartan 160 mg plus HCTZ 25 mg (V160/H25) in patients with stages 1 and 2 hypertension [15, 16]. A pooled analysis of these two studies provided support for the use of ARBs with this higher 25 mg dose of thiazide diuretic; furthermore, the analysis demonstrated that T80/H25 resulted in greater reductions in clinic BP than V160/H25 [17]. …”

“…In our pooled analysis of T80/H25 versus V160/H25, a substantial proportion of patients participating had stage (or grade) 2 hypertension [17]. The aim of the present analysis was to evaluate the efficacy and tolerability of both combination antihypertensive treatments in those patients who had moderate-to-severe hypertension, specifically defined as systolic BP (SBP) ≥ 160 mm Hg at baseline.…”