Losartan in cardiovascular disease

Abstract

Hypertension is a major risk factor for the development of cardiovascular disease. Numerous placebo-controlled trials have demonstrated that treatment of hypertension results in substantial reduction of hypertension-related vascular events. The benefit of specific therapies beyond their effect on blood pressure is well established. Losartan is an orally-active, selective, nonpeptide, angiotensin II type 1-receptor antagonist (ARB), and it was the first in this class to be marketed. Several large-scale clinical trials have demonstrated that losartan and other ARBs have benefits in preventing cardiovascular disease. The Losartan Intervention For End point reduction in hypertension (LIFE) study demonstrated improved outcomes with losartan as compared with atenolol-based therapies in hypertensive patients with left ventricular hypertrophy, mainly because of stroke prevention. The Reduction of End points in Non-insulin-dependent diabetes mellitus with the Angiotensin II Antagonist Losartan (RENAAL) study demonstrated that losartan prevented the progression of diabetic nephropathy. In this review, evidence from these and other clinical trials with losartan shall be discussed. The pharmacodynamic and pharmacokinetic properties of losartan are described to explain its mechanisms of action. Among the ARB class, losartan possesses certain unique properties, which may enhance its cardiovascular protective effects. These include an increase of urinary uric acid excretion and antiatherothrombotic properties. Potential future roles for losartan and other ARBs shall be discussed, in addition to emphasizing areas in which evidence is currently lacking or indecisive, including head-to-head comparisons of ARBs and the effects of combining an ARB with angiotensin-converting-enzyme inhibitors.