Use of an Olmesartan Medoxomil-Based Treatment Algorithm for Hypertension Control

Joel M. Neutel, MD; David H.G. Smith, MD; Michael A. Weber, MD; Antonia C. Wang, PhD; Harvey N. Masonson, MD

In This Article

Abstract and Introduction

Hypertension guidelines recommend a stepped-care approach that starts with titration of the initial agent followed by the addition of other agents, as necessary, to achieve goal blood pressure. This study assessed the effectiveness of an antihypertensive treatment algorithm with olmesartan medoxomil as the initial agent. This was a 24-week, open-label trial in patients (N=201) with mean seated diastolic blood pressure of 90-109 mm Hg. Following placebo run-in, all patients received olmesartan medoxomil 20 mg/d for 4 weeks. At subsequent 4-week intervals, the regimen was modified in patients with blood pressure >130/85 mm Hg: up-titration of olmesartan medoxomil to 40 mg/d; addition of hydrochlorothiazide 12.5 mg/d; up-titration of hydrochlorothiazide to 25 mg/d; addition of amlodipine besylate 5 mg/d; and up-titration of amlodipine besylate to 10 mg/d. Patients who achieved blood pressure ≤ 130/85 mm Hg at any point exited the study with no further follow-up. At Week 24, reductions in blood pressure from baseline were 33.7/18.2 mm Hg. Altogether, 87.7% of patients reached the goal blood pressure of ≤ 130/85 mm Hg and 93.3% achieved a blood pressure of ≤ 140/90 mm Hg. Thus, an antihypertensive algorithm with olmesartan medoxomil as the initial agent controlled blood pressure in the majority of patients, but with >60% of patients also requiring the use of a thiazide diuretic or a thiazide and a calcium channel blocker.

Reducing blood pressure (BP) decreases the risks of morbidity and mortality in patients with hypertension.[1,2,3] However, in practice, achieving the recommended BP goals of <140/90 mm Hg for patients with uncomplicated hypertension and <130/80 mm Hg for high-risk hypertensive patients such as those with concomitant diabetes, occurs infrequently. Only about 34% of people with hypertension in the United States have their BP controlled to <140/90 mm Hg, indicating a need for improved treatment. Although published guidelines recommend using a stepped-care antihypertensive treatment algorithm to reach these goals,[3] the effectiveness of this approach in clinical practice and the optimal selection of agents for each step remain undefined.

The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure[3] defines normal BP as <120/80 mm Hg and prehypertensive BP as 120-139/80-89 mm Hg. An analysis of 6859 normotensive participants in the Framingham Heart Study showed that persons with prehypertension had a significantly increased risk of developing both hypertension and cardiovascular (CV) disease compared with those whose entry BP was lower.[4]

The Hypertension Optimal Treatment (HOT) study[1] and the United Kingdom Prospective Diabetes Study (UKPDS 38)[2] both demonstrated that in hypertensive patients with diabetes, a more aggressive target BP was associated with improved cardioprotection. The HOT study also showed that self-reported well-being in all patients was highest in the treatment group assigned to the lowest diastolic blood pressure (DBP) goal ( ≤ 80 mm Hg). Importantly, at the end of the study, 77% of patients randomized to achieve a DBP of ≤ 80 mm Hg were taking two or more antihypertensive agents. In the UKPDS 38 trial,[2] many subjects required three or more medications to sustain the goal DBP of <85 mm Hg after 9 years of treatment. There is a need to demonstrate the ability of antihypertensive treatment protocols to lower BP to these aggressive goals in clinical practice.

Clinical studies indicate that angiotensin II receptor blocker (ARB) therapy provides antihypertensive efficacy comparable to that of other antihypertensive classes, and a tolerability profile similar to that of placebo.[5,6,7] Therapy based on an ARB has been shown to slow renal disease progression in hypertensive patients with diabetic renal disease, and to reduce CV morbidity and mortality in patients with hypertension with left ventricular hypertrophy and in patients with congestive heart failure.[8,9,10,11,12,13]

The ARB olmesartan medoxomil, the newest addition to the ARB class, is an efficacious antihypertensive agent.[14,15,16,17] This study was undertaken to assess in a clinical setting the percentage of patients with mild-to-moderate hypertension who would reach a goal BP of ≤ 140/90 mm Hg as well as a more aggressive goal BP of ≤ 130/85 mm Hg when physicians are provided with a specific BP goal and an algorithm designed to achieve that goal, using olmesartan medoxomil as the initial agent.