Although invasive procedures are commonly used early in the treatment of patients with unstable coronary artery disease (CAD), studies have yet to demonstrate reductions in myocardial infarction or mortality with this approach. As invasive and noninvasive management of unstable coronary artery disease have developed rapidly since the earlier studies, FRagmin and FRISC II investigators conducted a prospective randomized multicenter study to compare early invasive management with a noninvasive treatment strategy.
Between 1996 and 1998, 58 Scandinavian hospitals recruited more than 2,000 patients with symptoms of coronary ischemia that were increasing or occurring at rest. Myocardial ischemia was verified by electrocardiography or biochemical markers. Exclusions included recent revascularization procedures, concomitant serious noncardiac illness, age greater than 75 years and risk of adverse reaction to medications or treatments. Patients were randomly assigned to early invasive treatment or noninvasive therapy. Invasive treatments were selected to provide revascularization within seven days of entering the study for all patients with at least 70 percent obstruction in any artery supplying a substantial portion of the myocardium. Non-invasive therapy included maximal medical therapy as indicated for each patient. Within each group, patients were randomly assigned to receive subcutaneous low-molecular-mass heparin or placebo for three months. The patients, more than 550 in each of the four study groups, were monitored by clinic visits or telephone contact for 24 months.
Patients in the invasive treatment groups showed an initial increase in death or myocardial infarction, but after the first two weeks, the mortality and morbidity rates for the invasive treatment groups were lower than for patients treated with noninvasive strategies. After six months, myocardial infarction was significantly decreased, and the rate of rehospitalization halved in patients treated with early invasive strategies. The authors calculate a significant decrease in myocardial infarction alone (7.8 compared with 10.1 percent), a nonsignificant decrease in mortality (1.9 compared with 2.9 percent) and an improvement in the composite end point of death or myocardial infarction in the invasive group (9.4 compared with 12.1 percent). The invasive group reported an approximately 50 percent reduction in symptoms using standardized scoring scales for angina and a halving of the need for nitrates compared with the noninvasive group. Heparin therapy appeared to benefit patients in the noninvasive groups but did not contribute significantly to the outcome in patients in the early invasive treatment groups. Analysis of the study results by subgroups suggests that benefits of early revascularization were greatest in patients at highest risk.
The authors conclude that early invasive therapy provided significant decreases in death and myocardial infarction plus reductions in morbidity and improvement in symptoms in patients with unstable coronary artery disease. They advocate a change in conventional treatment of this condition to emphasize early revascularization and call for future research to focus on lowering the risks of revascularization procedures.
editor's note: The trend toward early revascularization treatment of unstable angina and related conditions is likely to be accelerated by this study. The results of early revascularization reported from Scandinavia are impressive, particularly as nearly 10 percent of “noninvasive” patients underwent procedures within the first 10 days and nearly 40 percent within six months, yet the results are reported by intention to treat. Before advocating dramatic changes, however, it should be noted that over 750 of the original 3,048 eligible patients were withdrawn or excluded from the study. Although the results of this study appear to indicate clear advantage for early revascularization, it is unclear if these results in carefully selected patients can be generalized to American populations. The increased mortality and morbidity rates for the first 30 days in patients treated invasively are particularly worrisome.—a.d.w.