Evaluation of antihypertensive therapy with the co

Authors: Chrysant Steven G Weber Michael A Wang Antonia C Hinman Donald J

Publish Date: 2004/03/01

Volume: 17, Issue: 3, Pages: 252-259

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Abstract

Steven G Chrysant Michael A Weber Antonia C Wang Donald J Hinman Evaluation of antihypertensive therapy with the combination of olmesartan medoxomil and hydrochlorothiazide American Journal of Hypertension Volume 17 Issue 3 March 2004 Pages 252–259 https//doiorg/101016/jamjhyper200311003Most patients with hypertension require more than one agent to control blood pressure BP The purpose of this study was to assess the efficacy and safety of the angiotensin II receptor blocker olmesartan medoxomil in combination with hydrochlorothiazide HCTZThis was a randomized doubleblind factorial design study After a placebo runin period eligible patients n = 502 with a baseline mean seated diastolic blood pressure SeDBP of 100 to 115 mm Hg were randomized to one of 12 groups placebo olmesartan medoxomil monotherapy 10 20 or 40 mg/day HCTZ monotherapy 125 or 25 mg/day or one of six groups of olmesartan medoxomil/HCTZ combination therapy The primary endpoint was the change in mean trough SeDBP from baseline at week 8 Statistical analyses were conducted to determine whether at least one combination produced a larger reduction in SeDBP at week 8 than the individual corresponding component doses but did not compare BP reductions with different combination dosesOlmesartan medoxomil plus HCTZ produced greater reductions in both SeDBP and seated systolic blood pressure SeSBP at week 8 than did monotherapy with either component All olmesartan medoxomil/HCTZ combinations significantly reduced SeDBP and SeSBP compared with placebo in a dosedependent manner Reductions from baseline in mean trough SeSBP/SeDBP were 33/82 mm Hg 201/164 mm Hg and 268/219 mm Hg with placebo olmesartan medoxomil/HCTZ 20/125 mg and olmesartan medoxomil/HCTZ 40/25 mg respectively All treatments were well toleratedWith only up to 34 of Americans with hypertension achieving a goal blood pressure BP of 140/90 mm Hg more aggressive and multifaceted modes of therapy are required1–3 Major studies have shown that most patients with hypertension need two or more antihypertensive drugs to achieve BP control4–7 Substantial evidence supports the efficacy of angiotensin II blockade using angiotensinconverting enzyme ACE inhibitors or angiotensin II receptor blockers ARBs to lower BP and to protect the heart and kidneys8–16 Based on these data the American Diabetes Association recommends the use of ACE inhibitors as firstline therapy for hypertensive patients with type 1 diabetic renal disease and ARB for those with type 2 diabetes and renal disease17Placebocontrolled clinical trials have shown that the BPlowering efficacy of olmesartan medoxomil monotherapy a longacting oncedaily ARB at its starting dosage 20 mg/day and maximal dosage 40 mg/day compares favorably with that of other antihypertensive agents such as atenolol captopril felodipine and amlodipine besylate as well as other ARBs in clinical efficacy trials18–22Hydrochlorothiazide HCTZ is a thiazide diuretic that is commonly used in combination with other antihypertensive agents including ARBs2324 Hydrochlorothiazide is known to activate the reninangiotensinaldosterone system RAAS providing a strong rationale for the combination of an ARB with HCTZ25–29 The objective of this factorial design study was to assess the efficacy and safety of olmesartan medoxomil in combination with HCTZ at various dosages compared with monotherapy with each drug and with placeboThis was a randomized doubleblind factorial design study conducted at 48 investigational sites in the United States Eligibility criteria for randomization included the following average SeDBP ≥100 and ≤115 mm Hg at both week 3 and week 4 placebo runin visits with at least 4 days between the two visits a difference of ≤7 mm Hg between the two SeDBP measurements and at least 80 compliance with the study drug regimen during the placebo runin period Patients with serious medical disorders and those with a body weight ≥50 of ideal body weight for height and frame size calculated according to the 1983 Metropolitan Life Insurance table were excluded The protocol and one amendment were reviewed and approved by either a central or local institutional review board at each of the investigational sites The study was conducted in accordance with institutional review board committee and informed consent regulations of 21 Code of Federal Regulations parts 50 and 56 and principles of the Declaration of Helsinki and its amendments Written informed consent was obtained from each study participant at the screening visit

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