IMPORTANCE OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS IN MYOCARDIAL-INFARCTION AND CONGESTIVE-HEART-FAILURE - IMPLICATIONS FOR CLINICAL-PRACTICE

Angiotensin-converting enzyme inhibitors (ACE inhibitors) have been shown to be effective in improving symptoms and survival in patients with systolic left ventricular dysfunction. Despite their proven benefits the use of ACE inhibitors is still limited in many parts of the western world. In part, the underutilization of ACE inhibitors is due to the occurrence of side effects such as cough, renal dysfunction and first dose hypotension. These side effects are in part due to ACE inhibitor-induced bradykinin formation. Blockade of the effects of angiotensin II can however also be achieved with an angiotensin II type I receptor blocking agent such as losartan. To determine the relative safety and effectiveness of ACE inhibitors compared to an angiotensin II type I receptor blocking agent the evaluation of losartan and the elderly trial (Elite) is comparing the ACE inhibitor captopril to the angiotensin II type I receptor blocking agent losartan in elderly patients. When used ACE inhibitors are often given in doses lower than those shown to be effective in reducing mortality in the major randomized trials. Several trials are currently under way comparing low to high doses of ACE inhibitors which should provide information on the need to achieve the doses used in the major mortality studies. The finding that there remains a considerable mortality in patients with left ventricular dysfunction despite the use of ACE inhibitors and that there may be an 'escape' of angiotensin II production despite the use of ACE inhibitors has led to the randomized angiotensin II receptor antagonists-ACE inhibitor study (RAAS) which has begun to explore the role of an angiotensin II type I receptor blocking agent in conjunction with an ACE inhibitor. In view of the observation that ACE inhibitors may reduce the occurrence of myocardial infarction in patients with systolic left ventricular dysfunction several trials are currently under way in patients without systolic left ventricular dysfunction to determine whether ACE inhibitors prevent the progression of coronary atherosclerosis and the occurrence of myocardial infarction (MI). Despite the many thousands of patients studied in randomized trials of ACE inhibitors, we are only at an early stage in our understanding of the potential of blocking the renin-angiotensin-aldosterone system (RAAS).