Correspondence
Primary Angioplasty versus Thrombolysis for Acute Myocardial Infarction
N Engl J Med 2000; 342:890-892March 23, 2000
- Article
To the Editor:
In the November 4 issue, Zijlstra et al.1 report a better long-term outcome after primary angioplasty than after thrombolysis in patients with acute myocardial infarction. Should the debate about the relative merits of angioplasty and thrombolytic therapy now be closed, as Faxon and Heger suggest in the accompanying editorial?2 We do not think so, since the discussion to date has focused on in-hospital thrombolysis, and the role of prehospital thrombolysis has been underestimated.
The time from the onset of symptoms to the initiation of treatment is a major determinant of the outcome after thrombolytic therapy.3 The delay in treatment can be reduced if the diagnosis of myocardial infarction and the subsequent initiation of therapy occur in the patient's home rather than in the hospital. When the data from all randomized trials of prehospital thrombolysis as compared with in-hospital thrombolysis, involving a total of 6607 patients, were combined, prehospital thrombolysis was associated with a gain of 1 hour (125 minutes vs. 186 minutes) (Figure 1Figure 1
Mortality Rate at 30 Days or at Hospital Discharge in All Randomized Trials of Prehospital as Compared with In-Hospital Thrombolytic Therapy.). As a result, prehospital treatment was associated with a significant absolute reduction of 1.7 percent in the mortality rate at 30 days or at discharge, and an 18 percent reduction in the odds of death (odds ratio, 0.82; 95 percent confidence interval, 0.70 to 0.97; P=0.02).The benefit of prehospital over in-hospital thrombolytic therapy is strikingly similar to the benefit of primary angioplasty over in-hospital thrombolysis. A recent meta-analysis of randomized trials, involving a total of 2606 patients, showed that primary angioplasty was associated with an absolute reduction of 2.1 percent in the mortality rate at 30 days or at discharge.4 The observed 34 percent reduction in the odds of death (odds ratio, 0.66; 95 percent confidence interval, 0.46 to 0.94; P=0.02) does not differ significantly from the reduction in the odds of death in the trials of prehospital thrombolysis (P=0.26 by the Breslow–Day test for the homogeneity of the two odds ratios).
Data on the long-term outcome of prehospital thrombolytic therapy as compared with in-hospital thrombolytic therapy are available only from the Grampian Region Early Anistreplase Trial. In this trial, the mortality rate at five years was 25.2 percent in the prehospital group and 35.8 percent in the in-hospital group (P=0.04).5 The reduction in the mortality rate with prehospital thrombolysis (odds ratio, 0.60; 95 percent confidence interval, 0.37 to 0.98) is similar to the reduction at five years with primary angioplasty, as reported by Zijlstra et al. (P=0.50 by the Breslow–Day test for the homogeneity of the two odds ratios).
In view of the excellent outcome after primary angioplasty, it should be considered the treatment of choice for acute myocardial infarction in well-equipped and experienced centers. The vast majority of patients, however, have no access to such facilities and will benefit more from on-site diagnosis and immediate thrombolytic therapy. Sophisticated portable electrocardiographic devices and easy-to-use thrombolytic agents (with bolus injections) are available to facilitate diagnosis and treatment in the patient's home.
5 ReferencesEric Boersma, Ph.D.
Martijn Akkerhuis, M.D.
Maarten L. Simoons, M.D., Ph.D.
University Hospital Rotterdam, 3015 GD Rotterdam, the Netherlands1
Zijlstra F ,Hoorntje JCA ,de Boer M-J , et al. Long-term benefit of primary angioplasty as compared with thrombolytic therapy for acute myocardial infarction. N Engl J Med 1999;341:1413-1419
Full Text | Web of Science | Medline2
Faxon DP, Heger JW. Primary angioplasty — enduring the test of time. N Engl J Med 1999;341:1464-5.
3
Boersma E ,Maas AC ,Deckers JW ,Simoons ML . Early thrombolytic treatment in acute myocardial infarction: reappraisal of the golden hour. Lancet 1996;348:771-775
CrossRef | Web of Science | Medline4
Weaver WD ,Simes RJ ,Betriu A , et al. Comparison of primary coronary angioplasty and intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review. JAMA 1997;278:2093-2098[Erratum, JAMA 1998;279:1876.]
CrossRef | Web of Science | Medline5
Rawles JM . Quantification of the benefit of earlier thrombolytic therapy: five-year results of the Grampian Region Early Anistreplase Trial (GREAT). J Am Coll Cardiol 1997;30:1181-1186
CrossRef | Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: The time from the onset of symptoms to the initiation of treatment is certainly related to the outcome after reperfusion therapy, mainly because of important differences in base-line clinical characteristics between patients who present early and those who present late after the onset of symptoms.1,2 Nevertheless, in addition to determinants such as the grade of blood flow according to the Thrombolysis in Myocardial Infarction (TIMI) classification after reperfusion therapy, age, hemodynamic status, and the location of the infarct, the outcome is determined by the time from the onset of symptoms to the initiation of therapy. When reperfusion therapy is effective, a one-hour gain, in particular during the first two hours of acute myocardial infarction, will result in additional myocardial salvage.3 This result may be independent of the way in which the patency of the infarct-related coronary artery is achieved, although primary angioplasty and thrombolysis differ with regard to the relation between the time to treatment and the outcome, with the outcome after angioplasty less dependent on time.4
We agree with Boersma et al. that earlier diagnosis with prehospital electrocardiography is an important development. We found that, as compared with the time to treatment with previous cohorts, 30 minutes or more is gained by prehospital diagnosis, because of the ability to make preparations before arrival at the hospital.5
We disagree with the statement by Boersma et al. that the benefit of prehospital thrombolysis is similar to that of primary angioplasty. A nonsignificant result of a Breslow–Day test for the homogeneity of odds ratios is not an appropriate way to show equivalence. In all the cited trials, including the studies of prehospital thrombolysis, the mortality rate was consistently lower after primary angioplasty. We think that the superiority of primary angioplasty is now firmly established, and that this technique should be considered the treatment of choice for acute myocardial infarction. With more than 1000 procedures performed per 1 million people per year in the United States and in many countries in Europe, primary angioplasty is an attractive option for many patients with acute myocardial infarction and has become part of “the real world” of medical practice.
5 ReferencesFelix Zijlstra, Ph.D.
Menko-Jan de Boer, Ph.D.
Hospital De Weezenlanden, 8011 JW Zwolle, the Netherlands1
Brodie BR ,Stuckey TD ,Wall TC , et al. Importance of time to reperfusion for 30-day and late survival and recovery of left ventricular function after primary angioplasty for acute myocardial infarction. J Am Coll Cardiol 1998;32:1312-1319
CrossRef | Web of Science | Medline2
van `t Hof AW ,Liem A ,Suryapranata H ,Hoorntje JC ,de Boer MJ ,Zijlstra F . Clinical presentation and outcome of patients with early, intermediate and late reperfusion therapy by primary coronary angioplasty for acute myocardial infarction. Eur Heart J 1998;19:118-123
CrossRef | Web of Science | Medline3
Liem AL , van `t Hof AW,Hoorntje JC ,de Boer MJ ,Suryapranata H ,Zijlstra F . Influence of treatment delay on infarct size and clinical outcome in patients with acute myocardial infarction treated with primary angioplasty. J Am Coll Cardiol 1998;32:629-633
CrossRef | Web of Science | Medline4
O'Neill WW ,de Boer MJ ,Gibbons RJ , et al. Lessons from the pooled outcome of the PAMI, Zwolle and Mayo Clinic randomized trials of primary angioplasty versus thrombolytic therapy of acute myocardial infarction. J Invasive Cardiol 1998;10:4A-10A
Medline5
van `t Hof AW ,Liem A ,Suryapranata H ,Hoorntje JC ,de Boer MJ ,Zijlstra F . Angiographic assessment of myocardial reperfusion in patients treated with primary angioplasty for acute myocardial infarction: myocardial blush grade. Circulation 1998;97:2302-2306
Web of Science | Medline
To the Editor:
Boersma and colleagues raise an important point that we did not make clearly in our editorial. We agree that prehospital thrombolysis can, in certain circumstances, result in earlier reperfusion and a reduction in the mortality rate. However, not all studies of prehospital thrombolysis have had positive results. In a comparison of studies that showed the greatest benefit with those that did not, the time between prehospital and in-hospital administration of thrombolytic agents was critical, with a benefit seen largely when the difference was greater than one hour. In the United States, particularly in metropolitan areas, the time between a “911 call” and admission to the emergency room is often very short. At our medical center, the average time is five minutes. Thus, the advantages of prehospital thrombolysis may be minimal when the time between the 911 call and arrival at the emergency room is short.
The use of prehospital thrombolysis does not, however, preclude a combined approach. As we pointed out in our editorial, the administration of thrombolytic therapy followed by angioplasty, an approach used in the Plasminogen-Activator Angioplasty Compatibility Trial,1 may offer the best of both techniques, by establishing early reperfusion and ensuring a TIMI grade 3 flow in nearly all patients. Studies evaluating prehospital thrombolysis and subsequent angioplasty are in the planning phase, and we eagerly await their results.
1 ReferencesDavid P. Faxon, M.D.
Joel W. Heger, M.D.
University of Southern California School of Medicine, Los Angeles, CA 900331
Ross AM ,Coyne KS ,Reiner JS , et al. A randomized trial comparing primary angioplasty with a strategy of short-acting thrombolysis and immediate planned rescue angioplasty in acute myocardial infarction: the PACT trial. J Am Coll Cardiol 1999;34:1954-1962
CrossRef | Web of Science | Medline
- Citing Articles (4)
Citing Articles
1
Marc Cohen, James Hoekstra. (2008) The use of adjunctive anticoagulants in patients with acute coronary syndrome transitioning to percutaneous coronary intervention. The American Journal of Emergency Medicine 26:8, 932-941
CrossRef2
Elisabeth Ståhle. (2004) Revascularization after treatment for acute ST‐elevation myocardial infarction – CABG is an option. Scandinavian Cardiovascular Journal 38:3, 135-136
CrossRef3
Sarah A. Spinler, Stephanie M. Inverso. (2001) Update on Strategies to Improve Thrombolysis for Acute Myocardial Infarction. Pharmacotherapy 21:6, 691-716
CrossRef4
Elisabeth Ståhle. (2000) Immediate Angioplasty for Acute Myocardial Infarction - A Valid Option?. Scandinavian Cardiovascular Journal 34:4, 357-359
CrossRef
