Using ACE Inhibitors Appropriately -- American Family Physician

www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 461 Renin-Angiotensin System The renin-angiotensin system is systemically and locally driven. The systemic process is triggered by the kidney’s response to decreased effective blood volume and begins with the secretion of renin from the renal cortex. Once released, renin cleaves angiotensinogen to form angiotensin I. This product, in turn, is catalyzed by angiotensin-converting enzyme, formed primarily in the pulmonary vasculature, into angiotensin II. This potent vasoconstrictor affects tissues and systems throughout the body; research shows that these vasoconstrictor effects are attenuated by ACE inhibition (Table 1). Local renin-angiotensin systems exist in all vascular endothelium. Vascular cells maintain local vasomotor tone homeostasis primarily through the elaboration of angiotensin II and nitric oxide, a potent vasodilator. If this mechanism becomes impaired by oxidative stress, the endothelium can no longer maintain vasomotor tone in response to local needs. This phenomenon, termed endothelial dysfunction, precedes and contributes to atherosclerosis. ACE inhibition attenuates endothelial dysfunction by decreasing the destruction of bradykinin, thereby enhancing production of nitric oxide. Clinical investigations support the benefits of ACE inhibition. The results of the Trial on C ardiovascular disease affects one in four Americans. According to the American Heart Association, heart and related diseases are expected to cost Americans more than $329 billion in 2002. An estimated 10 million persons in this country are known to have diabetes and 3.6 million to have renal disease, incurring annual health care costs of $98 billion and $11 billion, respectively. Although angiotensin-converting enzyme (ACE) inhibitors have documented clinical benefits in a variety of clinical situations, the disparity between the evidence from clinical trials and bedside medicine is well documented. The National Registry of Myocardial Infarction 2 found that fewer than one half of patients surviving acute myocardial infarction who were candidates for therapy with ACE inhibitors received these life-saving drugs at discharge. A recent review of patients with asymptomatic left ventricular dysfunction revealed an underuse of ACE inhibition (48 percent of eligible candidates) and a greater likelihood of being started on an ACE inhibitor if under the care of a cardiologist rather than a noncardiologist. In 2000, Bahit and colleagues reviewed actual versus ideal prescribing of drugs for secondary prevention after myocardial infarction and estimated that 30,600 lives would be saved annually by offering ACE inhibitors. When first introduced in 1981, angiotensin-converting enzyme (ACE) inhibitors were indicated only for treatment of refractory hypertension. Since then, they have been shown to reduce morbidity or mortality in congestive heart failure, myocardial infarction, diabetes mellitus, chronic renal insufficiency, and atherosclerotic cardiovascular disease. Pathologies underlying these conditions are, in part, attributable to the reninangiotensin-aldosterone system. Angiotensin II contributes to endothelial dysfunction, altered renal hemodynamics, and vascular and cardiac hypertrophy. ACE inhibitors attenuate these effects. Clinical outcomes of ACE inhibition include decreases in myocardial infarction (fatal and nonfatal), reinfarction, angina, stroke, end-stage renal disease, and morbidity and mortality associated with heart failure. ACE inhibitors are generally well tolerated and have few contraindications. (Am Fam Physician 2002;66:461-8,473. Copyright© 2002 American Academy of Family Physicians.) Using ACE Inhibitors Appropriately