For the past 20 years, large-scale ongoing controlled trials have randomized more than 120,000 patients to evaluate the effectiveness of angiotensin-converting enzyme (ACE) inhibitors during and after acute myocardial infarction. Earlier studies indicated that ACE inhibitors reduce myocardial infarction size and improve ventricular remodeling, both of which have a beneficial effect on morbidity and mortality in postinfarction patients who have evidence of left ventricular dysfunction. More recently, ACE inhibitors have been shown to be beneficial when given during the acute phase of myocardial infarction, within 24 to 36 hours of the onset of symptoms. Current guidelines of the American College of Cardiology (ACC) and the American Heart Association (AHA) state that oral ACE inhibitor therapy should be started within the first 24 hours of suspected acute myocardial infarction and continued for four to six weeks in patients without contraindications. Therapy should be continued for at least three years in patients with left ventricular dysfunction. Michaels and associates reviewed data from the National Registry of Myocardial Infarction 2 (NRMI 2), a large registry of patients treated for acute myocardial infarction at selected hospitals to identify whether these recommendations have had an impact on physician practice patterns.
A total of 275,560 patients were identified in the NRMI 2 over a two-year period as having received inpatient treatment following initial evaluation for acute myocardial infarction. Of these, 202,438 patients were included in the analysis. Patients were excluded if they were transferred to another hospital to receive treatment. Those who were treated with ACE inhibitors within 24 hours had lower rates of ventricular tachycardia and/or fibrillation and inpatient mortality. However, overall mean use was only 15 percent at baseline. Specific contraindications or poor tolerance of ACE inhibitors did not explain this low rate.
ACE inhibitors were prescribed more aggressively in patients who were likely to benefit the most from early treatment. Thus, older patients (mean age: 70.9 years), women, and patients with diabetes mellitus, hypertension, a history of prior stroke, congestive heart failure or myocardial infarction were more likely to be treated according to the ACC/AHA guidelines. Patients receiving thrombolytic therapy were less likely to receive early treatment, even though data support the early use of ACE inhibitors in these patients. Overall, the early use of ACE inhibitors increased by 23 percent by the end of the study period, suggesting that physicians were becoming more aware of the effectiveness of early treatment. In hospitals without open-heart surgery capabilities, a decreased use of early ACE inhibitor therapy was seen. However, in rural hospitals and in facilities without primary angioplasty capabilities, a greater use of early ACE inhibitor treatment was seen. Regional variations existed as well, with lower use in the South and Southeast.
The authors conclude that the current ACC/AHA guidelines need to be better incorporated into actual clinical practice. Although more physicians are prescribing ACE inhibitors in patients admitted with acute myocardial infarction, most patients do not receive this potentially life-saving treatment.
editor's note: Acute myocardial infarction is associated with abnormal autonomic nervous system function with high sympathetic and low parasympathetic activity that is typically manifested in the morning hours. Kontopoulos and associates describe the circadian pattern of these autonomic abnormalities, both of which are thought to play an important role in the development of cardiac arrhythmias and acute ischemic syndromes. The authors found that quinapril increased parasympathetic and decreased sympathetic modulation during the entire day, with maximal effect between 1 and 5 a.m., 8 and 11 a.m., and 7 and 10 p.m. Metoprolol essentially had the same effect but primarily between 8 a.m. and 12 noon and to a lesser degree between 7 and 10 p.m. This improvement of autonomic function in postinfarction patients may explain the benefit of ACE inhibitors, especially during the times of day when most adverse events occur. These findings suggest that ACE inhibitor therapy is useful in postinfarction patients with left ventricular systolic dysfunction and in patients with normal ventricular function.—r.s.