Dose-related antihypertensive effects of irbesartan in patients with mild-to-moderate hypertension

James L. Pool, Robert M. Guthrie, Thomas W. Littlejohn, Philip Raskin, Alexander M M Shephard, Michael A. Weber, Matthew R. Weir, Thomas W. Wilson, James Wright, Kenneth B. Kassler-Taub, Richard A. Reeves

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

Two multicenter, double-blind, placebo-controlled, parallel group studies were conducted to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of the angiotensin II receptor (AT1 subtype) antagonist irbesartan. The effect of irbesartan withdrawal and the effect of adding hydrochlorothiazide (HCTZ) to irbesartan were also assessed. After a placebo lead-in phase, all patients were randomized to 8 weeks of double-blind therapy with either placebo (n = 158) or irbesartan at doses of 1, 5, 10, 25, 50, 100, 200, or 300 mg (n = 731 total) orally once daily. Irbesartan reduced blood pressure in a dose-related manner. Reductions from baseline in trough seated diastolic blood pressure ranged from 7.5 mm Hg for 50 mg irbesartan to 11.6 mm Hg for 300 mg irbesartan. At week 8, statistically significant reductions over placebo were observed in trough seated blood pressure with all irbesartan doses ≤ 50 mg. These reductions reached statistical significance versus placebo within 2 weeks with 100, 200, and 300 mg irbesartan. Plasma irbesartan concentrations correlated with dose. Angiotensin II and aldosterone levels generally showed dose-related changes, consistent with AT1 receptor blockade. In patients not controlled at 8 weeks, the addition of 12.5 mg HCTZ resulted in further dose-related reductions in blood pressure. Irbesartan demonstrated a placebo-like safety profile and no dose-related toxicity. Irbesartan, administered alone or in combination with HCTZ, was well tolerated. Withdrawal of irbesartan did not result in rebound hypertension or adverse events. Thus, once-daily irbesartan is both an effective and safe antihypertensive agent for the treatment of mild-to-moderate hypertension.

Original languageEnglish (US)
Pages (from-to)462-470
Number of pages9
JournalAmerican Journal of Hypertension
Volume11
Issue number4 I
DOIs
StatePublished - Apr 1998

Fingerprint

irbesartan
Antihypertensive Agents
Hypertension
Placebos
Hydrochlorothiazide
Blood Pressure

Keywords

  • Angiotensin II receptor antagonist
  • Drug withdrawal
  • Hypertension
  • Irbesartan
  • Plasma renin activity

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Pool, J. L., Guthrie, R. M., Littlejohn, T. W., Raskin, P., Shephard, A. M. M., Weber, M. A., ... Reeves, R. A. (1998). Dose-related antihypertensive effects of irbesartan in patients with mild-to-moderate hypertension. American Journal of Hypertension, 11(4 I), 462-470. https://doi.org/10.1016/S0895-7061(97)00501-3

Dose-related antihypertensive effects of irbesartan in patients with mild-to-moderate hypertension. / Pool, James L.; Guthrie, Robert M.; Littlejohn, Thomas W.; Raskin, Philip; Shephard, Alexander M M; Weber, Michael A.; Weir, Matthew R.; Wilson, Thomas W.; Wright, James; Kassler-Taub, Kenneth B.; Reeves, Richard A.

In: American Journal of Hypertension, Vol. 11, No. 4 I, 04.1998, p. 462-470.

Research output: Contribution to journalArticle

Pool, JL, Guthrie, RM, Littlejohn, TW, Raskin, P, Shephard, AMM, Weber, MA, Weir, MR, Wilson, TW, Wright, J, Kassler-Taub, KB & Reeves, RA 1998, 'Dose-related antihypertensive effects of irbesartan in patients with mild-to-moderate hypertension', American Journal of Hypertension, vol. 11, no. 4 I, pp. 462-470. https://doi.org/10.1016/S0895-7061(97)00501-3
Pool, James L. ; Guthrie, Robert M. ; Littlejohn, Thomas W. ; Raskin, Philip ; Shephard, Alexander M M ; Weber, Michael A. ; Weir, Matthew R. ; Wilson, Thomas W. ; Wright, James ; Kassler-Taub, Kenneth B. ; Reeves, Richard A. / Dose-related antihypertensive effects of irbesartan in patients with mild-to-moderate hypertension. In: American Journal of Hypertension. 1998 ; Vol. 11, No. 4 I. pp. 462-470.
@article{bbb89a0110e4410980fa777ca432d61e,
title = "Dose-related antihypertensive effects of irbesartan in patients with mild-to-moderate hypertension",
abstract = "Two multicenter, double-blind, placebo-controlled, parallel group studies were conducted to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of the angiotensin II receptor (AT1 subtype) antagonist irbesartan. The effect of irbesartan withdrawal and the effect of adding hydrochlorothiazide (HCTZ) to irbesartan were also assessed. After a placebo lead-in phase, all patients were randomized to 8 weeks of double-blind therapy with either placebo (n = 158) or irbesartan at doses of 1, 5, 10, 25, 50, 100, 200, or 300 mg (n = 731 total) orally once daily. Irbesartan reduced blood pressure in a dose-related manner. Reductions from baseline in trough seated diastolic blood pressure ranged from 7.5 mm Hg for 50 mg irbesartan to 11.6 mm Hg for 300 mg irbesartan. At week 8, statistically significant reductions over placebo were observed in trough seated blood pressure with all irbesartan doses ≤ 50 mg. These reductions reached statistical significance versus placebo within 2 weeks with 100, 200, and 300 mg irbesartan. Plasma irbesartan concentrations correlated with dose. Angiotensin II and aldosterone levels generally showed dose-related changes, consistent with AT1 receptor blockade. In patients not controlled at 8 weeks, the addition of 12.5 mg HCTZ resulted in further dose-related reductions in blood pressure. Irbesartan demonstrated a placebo-like safety profile and no dose-related toxicity. Irbesartan, administered alone or in combination with HCTZ, was well tolerated. Withdrawal of irbesartan did not result in rebound hypertension or adverse events. Thus, once-daily irbesartan is both an effective and safe antihypertensive agent for the treatment of mild-to-moderate hypertension.",
keywords = "Angiotensin II receptor antagonist, Drug withdrawal, Hypertension, Irbesartan, Plasma renin activity",
author = "Pool, {James L.} and Guthrie, {Robert M.} and Littlejohn, {Thomas W.} and Philip Raskin and Shephard, {Alexander M M} and Weber, {Michael A.} and Weir, {Matthew R.} and Wilson, {Thomas W.} and James Wright and Kassler-Taub, {Kenneth B.} and Reeves, {Richard A.}",
year = "1998",
month = "4",
doi = "10.1016/S0895-7061(97)00501-3",
language = "English (US)",
volume = "11",
pages = "462--470",
journal = "Journal of clinical hypertension",
issn = "0895-7061",
publisher = "Oxford University Press",
number = "4 I",

}

TY - JOUR

T1 - Dose-related antihypertensive effects of irbesartan in patients with mild-to-moderate hypertension

AU - Pool, James L.

AU - Guthrie, Robert M.

AU - Littlejohn, Thomas W.

AU - Raskin, Philip

AU - Shephard, Alexander M M

AU - Weber, Michael A.

AU - Weir, Matthew R.

AU - Wilson, Thomas W.

AU - Wright, James

AU - Kassler-Taub, Kenneth B.

AU - Reeves, Richard A.

PY - 1998/4

Y1 - 1998/4

N2 - Two multicenter, double-blind, placebo-controlled, parallel group studies were conducted to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of the angiotensin II receptor (AT1 subtype) antagonist irbesartan. The effect of irbesartan withdrawal and the effect of adding hydrochlorothiazide (HCTZ) to irbesartan were also assessed. After a placebo lead-in phase, all patients were randomized to 8 weeks of double-blind therapy with either placebo (n = 158) or irbesartan at doses of 1, 5, 10, 25, 50, 100, 200, or 300 mg (n = 731 total) orally once daily. Irbesartan reduced blood pressure in a dose-related manner. Reductions from baseline in trough seated diastolic blood pressure ranged from 7.5 mm Hg for 50 mg irbesartan to 11.6 mm Hg for 300 mg irbesartan. At week 8, statistically significant reductions over placebo were observed in trough seated blood pressure with all irbesartan doses ≤ 50 mg. These reductions reached statistical significance versus placebo within 2 weeks with 100, 200, and 300 mg irbesartan. Plasma irbesartan concentrations correlated with dose. Angiotensin II and aldosterone levels generally showed dose-related changes, consistent with AT1 receptor blockade. In patients not controlled at 8 weeks, the addition of 12.5 mg HCTZ resulted in further dose-related reductions in blood pressure. Irbesartan demonstrated a placebo-like safety profile and no dose-related toxicity. Irbesartan, administered alone or in combination with HCTZ, was well tolerated. Withdrawal of irbesartan did not result in rebound hypertension or adverse events. Thus, once-daily irbesartan is both an effective and safe antihypertensive agent for the treatment of mild-to-moderate hypertension.

AB - Two multicenter, double-blind, placebo-controlled, parallel group studies were conducted to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of the angiotensin II receptor (AT1 subtype) antagonist irbesartan. The effect of irbesartan withdrawal and the effect of adding hydrochlorothiazide (HCTZ) to irbesartan were also assessed. After a placebo lead-in phase, all patients were randomized to 8 weeks of double-blind therapy with either placebo (n = 158) or irbesartan at doses of 1, 5, 10, 25, 50, 100, 200, or 300 mg (n = 731 total) orally once daily. Irbesartan reduced blood pressure in a dose-related manner. Reductions from baseline in trough seated diastolic blood pressure ranged from 7.5 mm Hg for 50 mg irbesartan to 11.6 mm Hg for 300 mg irbesartan. At week 8, statistically significant reductions over placebo were observed in trough seated blood pressure with all irbesartan doses ≤ 50 mg. These reductions reached statistical significance versus placebo within 2 weeks with 100, 200, and 300 mg irbesartan. Plasma irbesartan concentrations correlated with dose. Angiotensin II and aldosterone levels generally showed dose-related changes, consistent with AT1 receptor blockade. In patients not controlled at 8 weeks, the addition of 12.5 mg HCTZ resulted in further dose-related reductions in blood pressure. Irbesartan demonstrated a placebo-like safety profile and no dose-related toxicity. Irbesartan, administered alone or in combination with HCTZ, was well tolerated. Withdrawal of irbesartan did not result in rebound hypertension or adverse events. Thus, once-daily irbesartan is both an effective and safe antihypertensive agent for the treatment of mild-to-moderate hypertension.

KW - Angiotensin II receptor antagonist

KW - Drug withdrawal

KW - Hypertension

KW - Irbesartan

KW - Plasma renin activity

UR - http://www.scopus.com/inward/record.url?scp=0031748816&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031748816&partnerID=8YFLogxK

U2 - 10.1016/S0895-7061(97)00501-3

DO - 10.1016/S0895-7061(97)00501-3

M3 - Article

VL - 11

SP - 462

EP - 470

JO - Journal of clinical hypertension

JF - Journal of clinical hypertension

SN - 0895-7061

IS - 4 I

ER -