Thrombolytic Therapy in Acute Myocardial Infarction: Part II-rt-PA

Abstract

Thrombolysis with pharmacologic agents is a valuable modality for treatment of acute myocardial infarction. The results of several clinical studies indicate that early recanalization can be elicited with intravenous agents and that it is associated with substantial reductions of infarct size, improvement of ventricular function, and reduction in mortality. The recently introduced fibrin-selective agent, rt-PA, appears to represent a significant pharmacologic advance. Its use intravenously elicits high recanalization rates without marked derangements of the coagulation system, reflecting its relative fibrin selectivity. The efficacy of thrombolysis with any drug given by any route, unfortunately, is not 100 per cent. Bleeding remains an important risk. The optimal approach to management of residual stenosis after thrombolysis has not yet been delineated. Currently available information appears to justify the following conclusions: 1. Transmural myocardial infarction usually is caused by an acute obstructing coronary thrombus superimposed on a chronic atherosclerotic lesion. Myocardial necrosis following interruption of blood flow generally is complete within several hours. 2. The thrombus can be lysed and blood flow can be restored with intravenous agents that activate plasminogen. Intravenous rt-PA, a relatively fibrin-specific agent, elicits recanalization in 70 to 75 per cent of infarct-related arteries. 3. Recombinant t-PA evokes only modest depletion of fibrinogen (16 to 36 per cent reduction from baseline). 4. Early reperfusion preserves myocardium and ventricular function and reduces mortality. 5. The extent of benefit after pharmacologic reperfusion is correlated strongly with the brevity of myocardial ischemia prior to initiation of therapy. The greatest benefit is realized in patients treated within the first few hours of onset of acute myocardial infarction. 6. The incidence and optimal means of prevention of reocclusion and reinfarction following successful pharmacologic reperfusion are not yet entirely clear. Mechanical recanalization with PTCA in conjunction with thrombolysis is promising, but its routine immediate use on an emergency basis does not appear to be beneficial. Vigorous educational efforts are needed to heighten the awareness of prospective patients and all members of the health care team to the value of prompt diagnosis of incipient or evolving infarction so that prompt implementation of thrombolysis in appropriate candidates can be facilitated.