A Review of Olmesartan Medoxomil Monotherapy
Angiotensin II receptor blockers (ARBs) have been available in the United States since 1995. These agents have demonstrated antihypertensive efficacy at least similar to that of agents from other antihypertensive classes. Recent large-scale, randomized, controlled clinical trials have demonstrated that ARBs offer cardiovascular and renal protective benefits independent of their effects on systemic blood pressure (BP), which make them valuable as first-line antihypertensive agents, especially in high-risk patients. However, as is the case with other antihypertensive classes, monotherapy with the first-available ARBs (losartan potassium, valsartan, and irbesartan) may not provide sufficient BP reduction to achieve currently recommended BP goals in many patients. The diuretic hydrochlorothiazide is frequently added to enhance the ability of ARBs to lower BP. Several head-to-head comparison studies have shown differences in antihypertensive efficacy among the available ARBs. The newest ARB, olmesartan medoxomil, was recently compared with losartan potassium, irbesartan, and valsartan in a prospective, head-to-head, randomized trial. In this study, olmesartan medoxomil demonstrated a significantly greater reduction in diastolic BP, the primary end point, compared with the other three ARBs. Further, a review of the absolute reductions in diastolic BP achieved with olmesartan medoxomil monotherapy appears comparable to that of previously available ARBs when they are used in combination with hydrochlorothiazide. These comparisons may have important clinical implications regarding the optimal choice of first-line antihypertensive therapy.

The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) recommends a blood pressure (BP) goal of <140/90 mm Hg for the general hypertensive population and <130/85 mm Hg for high-risk patients with hypertension, including those with diabetes or renal disease. Other groups have published guidelines recommending even lower BP goals for high-risk individuals. However, data indicate that only about 25% of hypertensive individuals in the United States have their BP adequately controlled, even to the <140/90 mm Hg goal.

Up to one half of hypertensive individuals will fail to achieve appropriate BP goals with monotherapy, regardless of the class of antihypertensive agent used. Further, data from numerous large-scale clinical trials have demonstrated that the majority of patients with hypertension require two or more antihypertensive agents to achieve currently recommended target BP levels. However, the use of multiple antihypertensive drugs may lead to increased cost, more complicated medication regimens, and the potential for additional adverse effects and drug-drug interactions. These factors may in turn adversely affect compliance, which has a significant impact on treatment success. Other data suggest that long-term compliance is improved when the initial antihypertensive agent prescribed is both efficacious and well tolerated. It is important, therefore, for the initial antihypertensive agent used to provide as much BP-lowering efficacy as possible while maintaining optimal tolerability.

Angiotensin II receptor blockers (ARBs) have been available in the United States since 1995, and have demonstrated antihypertensive efficacy at least similar to that of agents from other antihypertensive classes. ARBs also offer an excellent tolerability profile, similar to that of placebo, based on the results of randomized, controlled clinical trials. ARBs lower BP by specifically blocking angiotensin II activity at angiotensin II subtype 1 receptor sites, thereby inhibiting the renin-angiotensin-aldosterone system, independent of the pathway of angiotensin II generation.

Inhibition of the renin-angiotensin-aldosterone system has been proved to convey clinical benefits independent of their effects on BP, as first demonstrated with angiotensin-converting enzyme inhibitors. ARBs have now also been shown to provide substantial cardiovascular and renal protection, independent of their effects on systemic BP. The excellent efficacy, safety, and tolerability of ARBs, along with their ability to provide end-organ protection, make them useful as first-line antihypertensive agents, particularly in high-risk individuals.

The introduction of ARBs, therefore, the latest advance in the treatment of hypertension, may potentially improve BP control rates due to their excellent efficacy and tolerability profile. However, as is the case with other antihypertensive classes, monotherapy with previously available ARBs generally does not reduce BP to recommended levels in most hypertensive individuals. Further, the older ARBs demonstrate limited dose-responsiveness; therefore, the BP-lowering effect of these agents is not likely to be significantly improved by simply increasing the dose. The addition of the diuretic hydrochlorothiazide (HCTZ) to ARB therapy has been shown to enhance the ability of ARBs to lower BP. However, an initial ARB monotherapy agent that yields sufficient antihypertensive efficacy in a broad range of patients with hypertension has not previously been available. Head-to-head comparison trials have shown differences in antihypertensive efficacy among the available ARBs. This review summarizes the antihypertensive efficacy of the newest ARB, olmesartan medoxomil, and assesses how olmesartan medoxomil monotherapy compares contextually with the leading ARBs when they are used both as monotherapy and in combination with HCTZ.