Reduction of Cardiovascular Risk through Angiotensin II Type 1 Receptor Antagonism : Focus on Olmesartan Medoxomil.
It is well recognized that angiotensin II is involved in the pathogenesis of hypertension. Less well recognized - until recently, at least - is its involvement in the pathogenesis of atherosclerosis. However, it is now evident that angiotensin II promotes oxidative stress, vascular remodelling, inflammation, and the formation of atherosclerotic lesions. These actions, which are mediated almost exclusively by the angiotensin II type 1 (AT(1)) receptor, can be blocked by administration of angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]). Of the seven ARBs currently in clinical use, olmesartan is one of the most effective. The rapid and consistent antihypertensive efficacy of this drug, which allows a high proportion of patients to achieve their target blood pressure (BP), is associated with beneficial effects on oxidative stress, vascular remodelling, inflammation, and atherosclerotic lesion formation. These effects appear to be independent of the BP-lowering activity of olmesartan. In clinical trials, olmesartan has been shown to control microinflammation in hypertensive patients, to reduce oxidative stress in patients with type 2 diabetes mellitus, and to normalize the wall: lumen ratio of small resistance arteries (a measure of vascular remodelling) in patients with hypertension. Moreover, in a 2-year study involving hypertensive patients with carotid atherosclerosis (the MORE [Multicentre Olmesartan atherosclerosis Regression Evaluation] trial), olmesartan reduced the intima-media thickness of the carotid artery and significantly reduced the volume of large atherosclerotic plaques. These data suggest that olmesartan may reduce cardiovascular risk by simultaneously normalizing BP and reversing the proatherogenic effects of angiotensin II.
Clinica Medica and Department of Medicine, University of Brescia, Brescia, Italy, agabiti@med.unibs.it.
Enrico Agabiti
EA
Rosei