Need for a prospective, randomized trial assessing the role of early coronary intervention following pharmacologic therapy for acute myocardial infarction.

P studies have demonstrated that an occlusive coronary arterial thrombus at the site of a ruptured plaque is the primary mechanism leading to a myocardial infarction. Thrombolytic agents, by restoring anterograde flow in the infarct-related artery, reduce infarct size and decrease mortality. Thrombolytic therapy, however, fails to establish anterograde flow in 15% to 20% of patients and is complicated by recurrent ischemia or infarction in 20% of patients. In addition, the Global Utilization of Streptokinase and TPA for Occluded arteries (GUSTO) angiographic substudy revealed that only 54% of patients treated with front-load, tissue-type plasminogen activator (tPA) had normal coronary flow (Thrombolysis In Myocardial Infarction [TIMI] 3 flow), an important finding because patients with TIMI 3 flow have lower mortality rates and greater preservation of left ventricular function than those with TIMI 2 flow. The realization that thrombolytic therapy is effective in establishing normal anterograde flow in one half of patients presenting with an acute ST-segment elevation myocardial infarction and is frequently complicated by recurrent ischemia and or reinfarction prompted investigators to perform 2 studies evaluating the role and timing of angiography and angioplasty. The TIMI IIA study addressed the issue of immediate versus delayed elective angioplasty after thrombolytic therapy. Patients with an acute ST-segment elevation myocardial infarction treated with thrombolytic therapy with a patent infarct-related artery at 90 minutes were randomized to immediate percutaneous transluminal coronary angioplasty (PTCA) versus delayed PTCA. There were no significant differences in left ventricular systolic function or subsequent reocclusion rates between the 2 groups. In fact, patients treated with immediate PTCA had increased rates of hemorrhagic complications and a trend toward an increased need for emergency bypass surgery. Thus, immediate PTCA did not confer a benefit over delayed PTCA in patients treated with thrombolytic drugs. However, this study did not address the need for routine coronary angiography after thrombolysis. The TIMI investigators compared invasive and conservative strategies after thrombolysis in acute myocardial infarction in the TIMI phase 2 trial. Patients were randomized to angiography and revascularization if the coronary anatomy was suitable, or to angiography and revascularization for spontaneous or exercise-induced ischemia. At 42 days, the primary composite end point of death or reinfarction occurred in 10.9% of the invasive group versus 9.7% of the ischemia-guided group. When combined, these 2 TIMI studies demonstrate that patients with an acute ST-segment elevation myocardial infarction treated with thrombolytic therapy should be managed with an ischemia-guided approach. Coronary angiography and revascularization should be reserved for recurrent ischemia, provocable ischemia, or mechanical complications such as cardiogenic shock, severe mitral regurgitation, or ventricular septal defect. In addition, patients with persistent pain and persistent ST-segment elevation may be considered for rescue angioplasty. Despite the results of these 2 studies, cardiologists often perform coronary angiography after apparently successful thrombolysis to assist in identifying patients at risk for reocclusion of the infarct-related artery. The GUSTO angiographic substudy has refuted this approach by demonstrating the inability to predict (based on angiographic parameters including TIMI flow) the presence of clot, lesion length, and stenosis severity, which infarct-related arteries are likely to reocclude. The performance of angiography in these patients often reveals severe stenoses which, in turn, are treated with percutaneous revascularization due to either clinical indications or to the “oculostenotic reflex.” In this issue of The American Journal of Cardiology, Schweiger et al (see page 831) describe the combined TIMI 10B-TIMI 14 experience of performing early percutaneous coronary intervention (PCI) in 1,938 patients with an acute ST-segment elevation myocardial infarction treated initially with pharmacologic therapy, and challenge the findings of the earlier TIMI studies. The clinical protocols used different pharmacologic regimens including tenecteplase, t-PA, retavase, and reduced doses of either t-PA, retavase, or streptokinase coupled with abciximab and heparin. The trial designs of both studies mandated coronary angiography at 90 minutes to determine infarct artery patency. The decision to proceed with coronary revasFrom the University of Texas Southwestern Medical Center, Dallas, Texas. Manuscript received and accepted May 29, 2001. Address for reprints: Joaquin Cigarroa, MD, University of Texas Southwestern Medical Center, Room CS 7.102, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9047.