Correspondence
Thrombolysis or Primary Angioplasty for Acute Myocardial Infarction?
N Engl J Med 1997; 336:1101-1103April 10, 1997
- Article
To the Editor:
In the clinical debate over the treatment of choice for acute myocardial infarction (Oct. 24 issue),1,2 Lange and Hillis argue in favor of thrombolysis. Table 2 in their rebuttal contains two important errors that may mislead many readers. First, the cited report by Eckman et al.3 is a pooled analysis that included 614 patients from the study by O'Keefe et al.,4 originally reported by Kahn et al.5 In addition, 383 patients from the study by Brodie et al.6 were included in the pooled analysis by Eckman et al.3 Therefore, 997 patients treated with primary angioplasty are represented twice.
Second, according to the reports by Brodie7 and O'Keefe et al.,4 a large proportion of the patients were not eligible for thrombolysis, and the mortality rate was lower among the candidates for thrombolysis who underwent primary angioplasty. Brodie7 reported that the candidates for thrombolysis had a mortality rate of 5.5 percent at 30 days, and O'Keefe et al.4 reported that those eligible for thrombolysis had an in-hospital mortality rate of only 3 percent.
7 ReferencesFelix Zijlstra, M.D.
Jan C.A. Hoorntje, M.D.
Menko-Jan de Boer, M.D.
Hospital de Weezenlanden, 8011 JW Zwolle, the Netherlands1
Lange RA ,Hillis LD . Should thrombolysis or primary angioplasty be the treatment of choice for acute myocardial infarction? Thrombolysis -- the preferred treatment. N Engl J Med 1996;335:1311-12, 1316
Full Text | Web of Science | Medline2
Grines CL . Should thrombolysis or primary angioplasty be the treatment of choice for acute myocardial infarction? Primary angioplasty -- the strategy of choice. N Engl J Med 1996;335:1313-16, 1317
Web of Science | Medline3
Eckman MH ,Wong JB ,Salem DN ,Pauker SG . Direct angioplasty for acute myocardial infarction: a review of outcomes in clinical subsets. Ann Intern Med 1992;117:667-676
Web of Science | Medline4
O'Keefe JH Jr ,Bailey WL ,Rutherford BD ,Hartzler GO . Primary angioplasty for acute myocardial infarction in 1,000 consecutive patients: results in an unselected population and high-risk subgroups. Am J Cardiol 1993;72:107G-115G
CrossRef | Web of Science | Medline5
Kahn JK ,O'Keefe JH Jr ,Rutherford BD , et al. Timing and mechanism of in-hospital and late death after primary coronary angioplasty during acute myocardial infarction. Am J Cardiol 1990;66:1045-1048
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Brodie BR ,Weintraub RA ,Stuckey TD , et al. Outcomes of direct coronary angioplasty for acute myocardial infarction in candidates and non-candidates for thrombolytic therapy. Am J Cardiol 1991;67:7-12
CrossRef | Web of Science | Medline7
Brodie BR . Primary angioplasty in a community hospital in the USA. Br Heart J 1995;73:411-412
CrossRef | Web of Science | Medline
To the Editor:
The authors of the clinical debate on the optimal reperfusion therapy for acute myocardial infarction make compelling arguments for each side in the controversy. Although the reader is presented with two very polarized interpretations of this issue, there are several recurring themes in the literature on the basis of which we can draw some firm conclusions.
First, the most effective type of acute reperfusion therapy is the one that the managing physician and medical center are most experienced with. The best outcomes with either intravenous thrombolysis or primary angioplasty are achieved by centers that perform large numbers of these procedures.
Second, high-risk patients appear to do better with primary angioplasty than with thrombolysis. Although thrombolytic therapy has been ineffective in lowering the high mortality rates associated with cardiogenic shock,1 in observational studies, primary angioplasty has reduced the shock-related mortality by approximately 50 percent (as compared with data from historical controls).1 The elderly also benefit from primary angioplasty.2-4
Third, both thrombolytic therapy and primary angioplasty are highly effective in salvaging jeopardized myocardium. Approximately 50 percent of the jeopardized myocardium is salvaged with timely reperfusion through either thrombolytic therapy or primary angioplasty.5 Patients with Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow have greater recovery of jeopardized myocardium after reperfusion therapy. Primary angioplasty results in a TIMI grade 3 flow in approximately 90 percent of patients (as compared with approximately 60 percent of patients receiving thrombolytic therapy).5
Finally, effective reperfusion therapy (either primary angioplasty or thrombolytic therapy) is the most important treatment for a patient presenting early in the course of an acute myocardial infarction.1 For most patients with acute myocardial infarction, the prompt and expert administration of reperfusion therapy is more important than the specific reperfusion strategy used.
5 ReferencesAnthony Magalski, M.D.
James H. O'Keefe, Jr., M.D.
Mid America Heart Institute, Kansas City, MO 641111
Ryan TJ ,Anderson JL ,Antman EM , et al. ACC/AHA guidelines for the management of patients with acute myocardial infarction. J Am Coll Cardiol 1996;28:1328-1428
CrossRef | Web of Science | Medline2
Lange RA ,Hillis LD . Should thrombolysis or primary angioplasty be the treatment of choice for acute myocardial infarction? Thrombolysis -- the preferred treatment. N Engl J Med 1996;335:1311-12, 1316
Full Text | Web of Science | Medline3
Grines CL . Should thrombolysis or primary angioplasty be the treatment of choice for acute myocardial infarction? Primary angioplasty -- the strategy of choice. N Engl J Med 1996;335:1313-16, 1317
Web of Science | Medline4
Grines CL ,Browne KF ,Marco J , et al. A comparison of immediate angioplasty with thrombolytic therapy for acute myocardial infarction. N Engl J Med 1993;328:673-679
Full Text | Web of Science | Medline5
Laster SB ,O'Keefe JH Jr ,Gibbons RJ . Incidence and importance of thrombolysis in myocardial infarction grade 3 flow after primary percutaneous transluminal coronary angioplasty for acute myocardial infarction. Am J Cardiol 1996;78:623-626
CrossRef | Web of Science | Medline
To the Editor:
In her rebuttal to Drs. Lange and Hillis, Dr. Grines raises the issue of equipoise and the ethics of clinical research. Equipoise is a state of uncertainty about the comparative merits of each treatment in a trial and is a required ethical condition in clinical research.
Dr. Grines suggests that because interventional cardiologists believe that percutaneous transluminal coronary angioplasty has “striking benefits” as compared with thrombolytic therapy, a trial comparing the two therapies would be “unethical.” Freedman has argued that the requirement for clinical equipoise is satisfied if there is uncertainty about a treatment not on the part of an individual investigator or a group of investigators, but within the expert medical community.1
As unsatisfying as it was to read the partisan arguments flying between the two camps, your inaugural clinical debate suggests clearly that such uncertainty exists.
1 ReferencesBruce Leff, M.D.
Johns Hopkins Geriatrics Center, Baltimore, MD 212241
Freedman B . Equipoise and the ethics of clinical research. N Engl J Med 1987;317:141-145
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Author/Editor Response
The authors reply:
To the Editor: We agree with Magalski and O'Keefe that both intravenous thrombolytic therapy and primary angioplasty are effective in restoring antegrade coronary flow in most patients with myocardial infarction. The more effective therapy is the one that can be administered more promptly, safely, and expertly. Some studies,1 but not all,2 suggest that primary angioplasty is preferable in certain high-risk patients (e.g., the elderly), and an ongoing prospective, randomized trial is attempting to determine whether primary angioplasty improves survival in patients with myocardial infarction and concomitant cardiogenic shock.
The studies cited by Zijlstra et al. showed that in large numbers of patients undergoing primary angioplasty, those said to be ineligible for thrombolytic therapy had a higher mortality than those considered to be eligible. In these studies, most of the patients thought to be ineligible for thrombolytic therapy were classified as such because of advanced age or presentation more than six hours after the onset of symptoms. However, in the smaller randomized trials comparing thrombolysis with primary angioplasty,1,3,4 as well as the several large trials of intravenous thrombolytic therapy, such patients were not considered ineligible for thrombolytic therapy. In short, caution must be exercised when comparing the results of these various studies.
As is evident from the data reported by Zijlstra et al., the in-hospital mortality among the patients considered to be eligible for thrombolysis and treated with primary angioplasty was higher in the larger trials than that reported in the smaller randomized trials,1,3-5 and was similar to that reported for patients given thrombolytic therapy in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) study and the study by Every et al.2 As the latter study showed, the mortality rates during hospitalization and at three years were similar for the patients treated with primary angioplasty and those treated with thrombolysis. Thus, these studies do not demonstrate the “striking benefits” of primary angioplasty. As Dr. Leff suggests, clinical equipoise exists.
5 ReferencesRichard A. Lange, M.D.
L. David Hillis, M.D.
University of Texas Southwestern Medical Center, Dallas, TX 75235-90471
Grines CL ,Browne KF ,Marco J , et al. A comparison of immediate angioplasty with thrombolytic therapy for acute myocardial infarction. N Engl J Med 1993;328:673-679
Full Text | Web of Science | Medline2
Every NR ,Parsons LS ,Hlatky M ,Martin JS ,Weaver WD . A comparison of thrombolytic therapy with primary coronary angioplasty for acute myocardial infarction. N Engl J Med 1996;335:1253-1260
Full Text | Web of Science | Medline3
Gibbons RJ ,Holmes DR ,Reeder GS ,Bailey KR ,Hopfenspirger MR ,Gersh BJ . Immediate angioplasty compared with the administration of a thrombolytic agent followed by conservative treatment for myocardial infarction. N Engl J Med 1993;328:685-691
Full Text | Web of Science | Medline4
Ribeiro EE ,Silva LA ,Carneiro R , et al. Randomized trial of direct coronary angioplasty versus intravenous streptokinase in acute myocardial infarction. J Am Coll Cardiol 1993;22:376-380
CrossRef | Medline5
Zijlstra F ,de Boer MJ ,Hoorntje JCA ,Reiffers S ,Reiber JHC ,Suryapranata H . A comparison of immediate coronary angioplasty with intravenous streptokinase in acute myocardial infarction. N Engl J Med 1993;328:680-684
Full Text | Web of Science | Medline
Author/Editor Response
In general, I agree with Magalski and O'Keefe's assessment of the controversy, with the exception of their statement that “the most effective type of acute reperfusion therapy is the one that the managing physician and medical center are most experienced with.” Although this view seems logical, there are limited data to support it. Most thrombolysis centers reserve primary percutaneous transluminal coronary angioplasty (PTCA) for patients who are at high risk or ineligible for thrombolytic therapy, and it is therefore not fair to compare outcomes between treatment groups. Registry data1,2 are further limited by the fact that the patients in the registry were not prospectively identified and were not randomly assigned to treatment, and no quality assurance was used to ascertain the accuracy of the retrospective data. Moreover, both the second Primary Angioplasty in Myocardial Infarction (PAMI II) study3 and the GUSTO-IIb substudy 4 found that the volume of procedures performed by a physician appeared to have no effect on the success of PTCA or the clinical outcome.
In response to Dr. Leff: what I stated in the clinical debate was that most physicians who perform primary PTCA believe that additional randomized trials would be unethical; these physicians would be unlikely to enter patients in such a trial. This point is exemplified by the GUSTO-IIb angioplasty substudy, in which patients were randomly assigned to treatment with accelerated tissue plasminogen activator or primary PTCA.4 Before the initiation of this trial, investigators at all 34 of our PAMI II clinical sites 3 were asked whether they wished to participate; investigators at only one site were willing to have patients randomly assigned to treatment. Moreover, despite the enrollment of patients at 57 clinical sites, recruitment was quite slow, and the GUSTO-IIb angioplasty substudy was terminated after 18 months without reaching the anticipated sample size.
4 ReferencesCindy L. Grines, M.D.
William Beaumont Hospital, Royal Oak, MI 48073-67691
Every NR ,Parsons LS ,Hlatky M ,Martin JS ,Weaver WD . A comparison of thrombolytic therapy with primary coronary angioplasty for acute myocardial infarction. N Engl J Med 1996;335:1253-1260
Full Text | Web of Science | Medline2
Rogers WJ ,Bowlby LJ ,Chandra NC , et al. Treatment of myocardial infarction in the United States (1990 to 1993): observations from the National Registry of Myocardial Infarction. Circulation 1994;90:2103-2114
Web of Science | Medline3
O'Neill WW ,Griffin JJ ,Stone G , et al. Operator and institutional volume do not affect the procedural outcome of primary angioplasty therapy. J Am Coll Cardiol 1996;27:Suppl A:13A-13A abstract.
CrossRef4
Ellis S. The GUSTO IIb angioplasty substudy. Presented at the American College of Cardiology Scientific Sessions, Orlando, Fla., March 27, 1996.
