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Source: Zijlstra F, et al. N Engl J Med 1999;341:1413-1419.
Prompt revascularization of the infarct-related artery (IRA) in acute myocardial infarction (MI) by thrombolytic therapy or direct angioplasty is proven to decrease mortality and morbidity. In 1993, two small, randomized trials of thrombolytic therapy vs. percutaneous transluminal coronary angioplasty (PTCA) suggested a benefit for PTCA, but other data were conflicting. This important report represents a five-year follow-up of the original Netherlands trial,1 and confirms a robust advantage of PTCA over streptokinase (SK). The PTCA group manifest increased survival, had fewer hospitalizations and invasive procedures, better LV function, less heart failure, and a lower clinical angina class compared to the SK cohort over a mean of 5 ± 2 years. Of the original 395 randomized subjects (194 PTCA, 201 SK), 16 of the angioplasty group received no procedure or coronary artery bypass graft (CABG). TIMI-3 flow was confirmed in 90% of the PTCA group vs. 65% of the SK cohort. This translated into better LV function at discharge in the PTCA patients (only 14% with LVEF < 40% vs 26% of the SK cohort). Late (5 ± 2 years) follow-up demonstrated a persistent advantage for primary angioplasty: total long-term mortality was 13% vs. 24%; nonfatal MI occurred in 6% vs. 22% (RR = 0.27). All recurrent infarcts were documented to occur in the IRA. The primary end point of death and nonfatal MI was markedly reduced during long-term follow-up; reinfarctions were considerably higher in the SK patients, as were readmissions for ischemia or heart failure. Interestingly, total medical charges per patient were comparable, and actually lower in alive PTCA subjects at the end of follow-up.
Zijlstra and colleagues conclude that the major factor explaining the results is the higher early patency rates in PTCA subjects, resulting in better LV systolic function, less reinfarction, and improved survival. Reinfarction rates in the IRA were high in the lytic therapy subjects.
Comment by Jonathan Abrams, MD
These data are impressive and confirm the findings of a (short-term) meta-analysis of 10 trials assessing early morbidity and mortality,2 and a new long-term meta-analysis.3 Moreover, the long-term results are reassuring, indicating that the PTCA patients do not develop an increased late hazard. The Kaplan-Meier survival curves are relatively parallel for mortality and nonfatal reinfarction after the first 30 days. While not discussed by Zijlstra et al, anterior infarction was an independent risk factor for death or MI; although data are not provided, it is possible that the benefits of PTCA are somewhat less in inferior infarcts. Other analyses have not been consistent regarding outcomes in anterior vs. inferior MI.
There are several caveats. Streptokinase does not result in TIMI-3 flow at 90 minutes in the majority of patients. Front-loaded t-PA vs. angioplasty would be likely to produce a smaller difference in outcomes. On the other hand, the use of stents during primary angioplasty, as well as therapy with platelet IIb-IIIa inhibitors, might result in even better PTCA outcomes.
Nevertheless, long-term cardiac mortality was three-fold greater in the SK patients vs PTCA (2% vs 7%; P < 0.001); this outcome is impressive. Of the subjects initially randomized to PTCA, nine were treated conservatively and seven underwent urgent CABG. The intention to treat analysis does not allow one to know the possible influence of these 16 subjects who did not receive a PTCA on short- and long-term events.
It now seems clear that, in experienced hands, within an appropriate time window, direct or primary angioplasty is preferred in most patients. One recent report suggests that time to intervention may be more critical to outcome in lytic patients than direct PTCA. New thrombolytic agents and lytic combinations with IIb-IIIa inhibitors, as well as the increasing use of stents, will keep this subject on the front burner for years to come.
1. Zijlstra F, et al. N Engl J Med 1993;328:680-684.
2. Weaver WD, et al. JAMA 1997;273:2093-2098.
3. Grines C, et al. Circulation 1999;100:I-499.
Dr. Abrams is Professor of Medicine, Division of Cardiology, University of New Mexico, Albuquerque.