Abstract :
When first developed, angiotensin-converting enzyme (ACE) inhibitors were believed to exert their major effects as vasodilators that blocked formation of angiotensin II, and therefore blocked angiotensin II-induced vasoconstriction and aldosteroneʹs effect on sodium and water retention. These agents were evaluated for their abilities to reduce blood pressure and cardiac preload and afterload in heart failure. The cardiovascular adverse outcomes most influenced were reductions in hemodynamic-related end-points such as hypertension and congestive heart failure.
In recent years, much has been learned about the renin-angiotensin system (RAS) and the potential utility of ACE inhibitors in the spectrum of cardiovascular disease. Evidence that local RASs exist in tissues such as the heart and vasculature and these may interact with the circulating RAS or act independently has stimulated considerable interest into the potential role of ACE activity and its inhibition in the development and progression of atherosclerosis. By inhibiting angiotensin II formation and increasing bradykinin levels locally, ACE inhibition may offer a multimechanistic means of protecting the vasculature. This intriguing possibility would extend the beneficial effects of ACE inhibitors to reduction of ischemic-related adverse outcomes.
Landmark clinical studies (eg, SOLVD, SAVE, and more recently AIRE, GISSI-3 and ISIS-4) that provide convincing evidence that ischemic events were reduced with ACE inhibitor therapy have heightened interest in whether these agents act to halt, slow progression, or stabilize atherosclerosis in patients without left ventricular dysfunction. Several major ongoing or planned clinical studies are evaluating the effects of ACE inhibitors on reducing ischemic events and/or slowing atherosclerotic disease progression in patients without left ventricular dysfunction.
