Matrix study of irbesartan with hydrochlorothiazide in mild-to-moderate hypertension

Abstract

The purpose of this study was to assess the safety and antihypertensive dose-response effects of irbesartan and hydrochlorothiazide (HCTZ) in patients with mild-to-moderate hypertension. After a 4- to 5-week single-blind placebo lead-in period, 683 patients with seated diastolic blood pressure (SeDBP) between 95 and 110 mm Hg were randomized to receive once-daily dosing with one of 16 different double-blind, fixed combinations of irbesartan (0, 37.5, 100, and 300 mg irbesartan) and HCTZ (0, 6.25, 12.5, and 25 mg HCTZ) for 8 weeks. The primary efficacy variable was the change from baseline in trough SeDBP after 8 weeks of therapy. Data were analyzed by response surface modeling. At Week 8, mean changes from baseline in trough SeDBP (mm Hg) ranged from -3.5 for placebo, -7.1 to -10.2 for the irbesartan monotherapy groups, -5.1 to -8.3 for the HCTZ monotherapy groups, and -8.1 to -15.0 for the combination groups. Irbesartan plus HCTZ produced additive reductions in both SeDBP and seated systolic BP, with at least one combination producing greater BP reduction than either drug alone (P < .001). All treatments were well tolerated; there were no treatment-related serious adverse events. Irbesartan tended to ameliorate the dose-related biochemical abnormalities associated with HCTZ alone. In conclusion, the combination of HCTZ in doses up to 25 mg with irbesartan, in doses up to 300 mg, is safe and produces dose-dependent reductions in BP.

Efficacy and tolerability of a fixed-dose combination of telmisartan plus hydrochlorothiazide in patients uncontrolled with telmisartan monotherapy

“…A similar corrective effect on serum potassium levels has also been observed when irbesartan, another AT 1 receptor antagonist, is co-administered with HCTZ. 17 In conclusion, our study has shown that oncedaily treatment with a fixed-dose combination of telmisartan 80 mg/HCTZ 12.5 mg offers superior efficacy to telmisartan 80 mg in patients with mild-tomoderate hypertension uncontrolled on telmisartan alone. This fixed-dose combination is also well tolerated.…”

“…For example, activation of the renin-angiotensin-aldosterone system (RAAS) by HCTZ amplifies the effects of agents acting through blockade of this pathway, including AT 1 receptor antagonists. [16][17][18][19][20][21] Combination of HCTZ with agents acting on the RAAS also has the potential to ameliorate the potassium depletion commonly associated with thiazide diuretic therapy. 17,22,23 A fixed-dose combination of telmisartan 80 mg/HCTZ 12.5 mg has been developed for the treatment of patients with mild-to-moderate hypertension.…”

“…[16][17][18][19][20][21] Combination of HCTZ with agents acting on the RAAS also has the potential to ameliorate the potassium depletion commonly associated with thiazide diuretic therapy. 17,22,23 A fixed-dose combination of telmisartan 80 mg/HCTZ 12.5 mg has been developed for the treatment of patients with mild-to-moderate hypertension. The doses selected were based on a previous dose-response study showing that telmisartan 80 mg has greater antihypertensive efficacy than telmisartan 40 mg, but further dose increase confers no extra therapeutic benefit.…”

Diuretics in the therapy of hypertension

“…[13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][36][37][38][39][40][41][42] The only biochemical variable that is affected by most antihypertensive diuretics irrespective of the dose is serum uric acid concentration, which undergoes a small increase, on average, even when low doses are used. 13,21,43 Cicletanine 50 mg does not modify the renal handling of urate, 44 and it does not elevate serum uric acid concentration.…”

Diuretics in the treatment of patients who present congestive heart failure and hypertension

“…The angiotensin II receptor antagonist losartan has been found to increase the renal excretion of urate in healthy subjects, 95 and both losartan and irbesartan have been found to attenuate hydrochlorothiazide-induced increases in serum uric acid in hypertensive patients. 96,97 Changes in acid-base balance Potassium-retaining diuretics cause renal retention of hydrogen ions and thereby tend to provoke acidosis, 48 particularly in patients at risk such as individuals who present renal insufficiency, subjects who also suffer from insulin-dependent diabetes and elderly persons.…”