Clinical Differences among Angiotensin II Receptor Antagonists

The six major classes of antihypertensive agents prescribed worldwide are similar in efficacy but dissimilar in tolerability. Recently, the World Health Organization-International Society of Hypertension (WHO-ISH) concluded that agents from all six classes are suitable for the initiation and maintenance of antihypertensive therapy, including the newest class of agents, the angiotensin II receptor antagonists (AIIRAs). The ideal antihypertensive agent should be effective and well tolerated, as well as synergistic in blood pressure-lowering effects when combined with other agents. As monotherapy, AIIRAs have demonstrated efficacy similar to other classes of antihypertensive agents in numerous clinical trials. Several AIIRAs have also demonstrated enhanced efficacy when combined with a low dose of the diuretic hydrochlorothiazide (HCTZ). A well-known feature of this new class of agents is placebo-level tolerability; however, less is known about intra-class differences. Losartan, the first approved AIIRA, has become an important benchmark for within-class comparisons with respect to antihypertensive efficacy. Head-to-head comparisons between losartan and newer AIIRAs have been conducted; their cumulative results indicate that the antihypertensive effect and antagonistic activity of losartan may be the weakest among AIIRAs. In a recent clinical trial, we demonstrated that irbesartan produces statistically superior blood pressure reduction when compared to valsartan. This may have clinical implications for agent selection among the AIIRAs.