Special Feature

Reperfusion Therapy in Acute Myocardial Infarction: Thrombolysis vs. Primary Angioplasty

By William J. Brady, MD

Re-establishing perfusion in the infarct-related coronary artery with the use of thrombolytic therapy (in essence re-opening the infarct-related artery) increases the opportunity for salvage of ischemic myocardium and, consequently, reduces morbidity and mortality. Thrombolytic therapy unequivocally improves survival in patients presenting with ST segment elevation (STE) acute myocardial infarction (AMI). Numerous, large thrombolytic investigations have supported this statement; a meta-analysis of nine major investigations of thrombolytic therapy in patients with AMI demonstrated approximately a 20% reduction in short-term mortality with the use of such agents compared to placebo. When all patient groups were pooled, a reduction of 18 deaths per 1000 patients treated was found.

While thrombolytic therapy has widespread availability and a proven ability to improve coronary flow, limit infarct size, and improve survival in AMI patients, many individuals with acute infarction are not considered suitable candidates for such treatment. Patients with absolute contraindications to thrombolytic therapy, certain relative contraindications cardiogenic shock, and unstable angina may be ineligible to receive thrombolytic therapy. The benefits of administering prompt reperfusion therapy to these patients, as well as other limitations of thrombolytic therapy, have led many clinicians to advocate percutaneous transluminal coronary angioplasty (PTCA) as the primary therapy and treatment of choice for AMI. Primary PTCA has many theoretical advantages over thrombolysis, including an increased number of eligible patients; a lower risk of intracranial bleeding; a significantly higher initial reperfusion rate; an earlier definition of coronary anatomy, with rapid triage to surgical intervention; and risk stratification allowing safe, early hospital discharge.

Results of Comparative Trials

Several trials of varying sizes comparing primary PTCA with thrombolysis have been reported in the past 10 years. Despite a clear and consistent benefit of primary PTCA in restoring patency of the infarct-related artery, differences in mortality in the individual trials were difficult to evaluate because of the relatively small sample sizes in the studies. More recent studies, however, suggest that PTCA is a superior therapy for the AMI patient. The PAMI trial enrolled 395 patients who were randomly assigned to primary PTCA vs. t-PA.1 Compared with standard-dose t-PA, primary PTCA reduced the combined occurrence of nonfatal reinfarction or death, was associated with a lower rate of intracranial hemorrhage, and resulted in similar left ventricular function. The results of the Netherlands trial indicated that primary angioplasty was associated with a higher rate of patency of the infarct-related artery, a less severe residual stenotic lesion, better left ventricular function, and less recurrent myocardial ischemia and infarction than in patients receiving streptokinase.2

In a substudy of the GUSTO IIb trial, the authors randomly assigned 1138 patients with AMI to either primary PTCA or accelerated t-PA.3 The composite end point of the study included death, nonfatal reinfarction, and nonfatal disabling stroke, all occurring within 30 days of the AMI. Of those patients assigned to primary PTCA therapy, 83% were candidates for such treatment and underwent angioplasty 1.9 hours after emergency department (ED) arrival for a total elapsed time from chest pain onset to therapy of 3.8 hours. Ninety-eight percent of the patients assigned to thrombolytic therapy received t-PA 1.2 hours after hospital arrival. The occurrence of the composite end point was encountered significantly less often in the PTCA group (9.6%) compared to the t-PA group (13.7%) at 30 days. When the individual components of the composite end point at 30 days were considered separately, the incidence of death (5.7% vs 7%), reinfarction (4.5% vs 6.5%), and stroke (0.2% vs 0.9%) occurred at statistically similar rates in both treatment groups—PTCA and t-PA—respectively. Additional work in the form of a meta-analysis by Weaver and colleagues reviewed 10 major studies comparing thrombolysis to primary PTCA in more than 2600 patients.4 The 30-day mortality was found to be significantly lower in the PTCA group (4.4%) than in patients treated with thrombolytics (6.5%). Primary PTCA also was associated with a significant reduction in total stroke rate and hemorrhagic strokes.

The longer-term results of primary PTCA, however, are less clear. The GUSTO IIb study showed no overall mortality advantage of primary PTCA at six months.3 Conversely, two-year follow-up from the PAMI trial found a significant reduction in hospital readmission, recurrent ischemia, target vessel revascularization, and reinfarction, with a trend toward a reduction in mortality in the PTCA group, compared to treatment with thrombolysis.1

Time Is Important

It is widely accepted that the early restoration of perfusion in the AMI patient limits myocardial damage, preserves left ventricular function, and reduces mortality; such restoration may be accomplished by either thrombolytics or PTCA. The rapid application of reperfusion therapy is a must in the patient with STE AMI. Emergency and cardiovascular physicians must consider many factors regarding early reperfusion treatment decisions when managing the AMI patient. While primary angioplasty may offer improved outcome over thrombolysis, PTCA must be applied early without prolonged delay. It must be stressed that PTCA should be initiated within 90 minutes of arrival at the hospital ED.5,6 (See Figure on pg. 29.) If the time required to mobilize staff and arrange for PTCA is prolonged (i.e., greater than 90 minutes to balloon catheter inflation across the culprit coronary lesion), then thrombolysis is preferred, assuming the patient is a candidate for thrombolysis. Delays beyond this time period are unacceptable if the patient originally was a thrombolytic candidate. Prior agreement between the ED and the cardiovascular physicians at institutions with angioplasty capability must be obtained so that PTCA consideration will not introduce further delays in thrombolytic drug administration. Such cooperation has been shown to limit additional delays in the administration of thrombolytic agents in AMI patients who are considered for PTCA.

The emergency physician must consider several related issues. First, the literature base to answer this question is somewhat heterogeneous (e.g., differing therapies, study sites, outcome measures), making absolute, all-encompassing recommendations impossible and thus providing fuel for further debate. Second, the question of technical expertise should be considered. In the GUSTO-IIb trial, the vast majority of physicians performed at least 75 procedures per year;3 these results may not generalize to smaller-volume centers with less-experienced operators. Third, the urgent transfer of a thrombolytic-eligible AMI patient to another institution for primary PTCA is not recommended until thrombolytic therapy is initiated; the delay in restoring perfusion in such a patient is not acceptable in most instances. If the patient is an acceptable candidate for thrombolysis, the thrombolytic agent should be started before or during transport to the receiving hospital. v

References

1. Grines CL, et al. A comparison of immediate angioplasty with thrombolytic therapy for acute myocardial infarction. N Engl J Med 1993;328:673.

2. Zijlstra F, et al. A comparison of immediate coronary angioplasty with intravenous streptokinase in acute myocardial infarction. N Engl J Med 1993;328:680.

3. The GUSTO IIb Angioplasty Substudy Investigators. A clinical trial comparing primary coronary angioplasty with tissue plasminogen activator for acute myocardial infarction. N Engl J Med 1997;336:1621.

4. Weaver WD, et al. Comparison of primary coronary angioplasty and intravenous thrombolytic therapy for acute myocardial infarction: A quantitative review. JAMA 1997;278:2093.

5. Ryan TJ, et al. 1999 Update: ACC/AHA guidelines for the management of patients with acute myocardial infarction. J Am Coll Cardiol 1999;34:890.

6. Ryan TJ, et al. ACC/AHA guidelines for the management of patients with acute myocardial infarction: Executive summary. Circulation 1996;94:2341.