The role of angiotensin antagonism in stroke prevention in patients with hypertension: focus on losartan.

Optimal management of hypertension has been shown to reduce the risk of stroke. In recent years, newer classes of antihypertensive such as the angiotensin II (Ang II) antagonists have become available. Results from the Losartan Intervention for Endpoint reduction in hypertension (LIFE) study suggest the utility of this particular Ang II antagonist in stroke prevention. Treatment with a losartan-based regimen or an atenolol-based regimen produced similar reductions in blood pressure during almost 5 years of follow up. Losartan, however, reduced the risk of stroke by 25% compared with atenolol (p = 0.001). For a subgroup of patients with isolated systolic hypertension, losartan reduced the risk of stroke by 40% (p = 0.02). As well as blocking the Ang II type 1 receptor, losartan also acts as an antagonist at the thromboxane A2 receptor and has uricosuric effects, which may provide additional mechanisms by which losartan provides protective benefits beyond its antihypertensive action. The relevance of these molecular properties of losartan over other Ang II antagonists is further supported by comparison of the outcomes obtained in clinical trials employing two other Ang II antagonists, valsartan and candesartan.