WHO SHOULD BE TREATED WITH ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS AFTER MYOCARDIAL-INFARCTION

Angiotensin-converting enzyme (ACE) inhibitors are now established dru gs in the treatment of hypertension and heart failure. However, their use in patients after a myocardial infarction has occurred remains con troversial. The major clinical question regarding ACE inhibitors is wh ether they should be given to all patients immediately after thromboly sis or whether their use should be restricted to a particular subgroup . This question has now been addressed in several large-scale trials o f mortality after myocardial infarction, and no important new informat ion seems likely to emerge on the issue. Clinicians must therefore dec ide what their practice will be on the basis of data that are currentl y available. The authors of the recently published Gruppo Italiano per lo Studio della Sopravvivenza nell' Infarcto Miocardico (GISSI-3) and Fourth International Study of Infarct Survival (ISIS-4) mega-trials a dvocate a policy of widespread and early use of ACE inhibitors in all patients after myocardial infarction occurs. However, the small mortal ity benefit observed from use of ACE inhibitors in these studies lacks certainty and may prove difficult to reproduce in the general populat ion of patients who have had an infarct outside the setting of a trial . Although patients were essentially not selected apart from the exclu sion of those with marked hypotension, the low 6-month and I-year mort ality figures indicate ''selection'' compared with the typical populat ion of patients who have had a myocardial infarction. Furthermore, a s ignificant long-term mortality benefit was not observed with the short -term (4- to 6-week) use of ACE inhibitors in these trials. In contras t, in the Survival and Ventricular Enlargement (SAVE), Acute Infarctio n Ramipril Efficacy (AIRE), and Trandopril Cardiac Evaluation (TRACE) trials, where evidence of impairment of ventricular function was used to select patients, both a marked and certain benefit regarding mortal ity was apparent from long-term prescription of these drugs. Important ly, the marked benefit observed in these selected patients may have be en ''diluted out'' in the larger scale trials of unselected patients w here the majority may have gained little and some may have been harmed by treatment or its withdrawal. In most of the large mortality trials the rationale for use of ACE inhibitors after myocardial infarction w as stated to be their likely beneficial effect on ''remodeling'' of th e heart after ''infarct expansion.'' Because adverse remodeling occurs in only a proportion of patients after a heart attack, the benefits o f ACE inhibitor therapy might be predicted to be largely limited to th is group, which would favor a selective policy. However, strong claims have been made that ACE inhibitors have other important actions, incl uding prevention of myocardial infarction. If this is confirmed in a n umber of ongoing large-scale trials, then an even more widespread use of these agents can be expected.