Revascularization After Myocardial Infarction
To the Editor:
Madsen et al1 compared an invasive strategy of coronary arteriography and revascularization with a conservative strategy in patients with inducible myocardial ischemia after thrombolysis for a first myocardial infarction. Just over 500 patients aged ≤69 years and able to perform an exercise test were randomized to each strategy. The invasive-strategy patients underwent 266 angioplasty procedures and 147 bypass operations. There was no significant difference in mortality between the 2 groups at a median of 2.4 years. Rates of reinfarction and of readmission for unstable angina were 5.6% and 17.9%, respectively, for the invasive strategy and 10.5% and 29.5%, respectively, for the conservative strategy. From this, Madsen et al conclude that all subjects with inducible ischemia after a thrombolyzed first myocardial infarction should be revascularized and then extend this sweeping recommendation, without any analysis of costs, days hospitalized, and quality of life, to all postinfarction patients with inducible ischemia.
It is unclear why in this study the invasive strategy’s absolute reduction of only 4.9% in the occurrence of myocardial infarction and of 11.6% in the number of admissions for unstable angina over 2.4 years, statistical significance notwithstanding, with no demonstrated reduction in mortality, constitutes sufficient clinical justification for sending all patients with inducible ischemia for coronary revascularization. Should patients with inducible ischemia who are symptomatic and limited to ≤5 metabolic equivalents (METs) be managed in the same way as asymptomatic patients with inducible ischemia performing ≥7 METs or >10 METs? Should all patients be similarly treated regardless of the degree of ST-segment depression or regardless of the threshold at which ischemia appears? Why should their risk be assumed to be the same? The study by Madsen et al provides no information on the occurrence of events in these clinically pertinent subsets of patients with inducible ischemia. Furthermore, it is questionable to randomize patients with inducible ischemia and a poor exercise performance (<5 METs), because several studies in both stable angina and after myocardial infarction have shown that such patients have a poor prognosis and therefore should undergo an “invasive strategy.”2 3 4 5 6 7 The randomization of such patients loads the question being asked in favor of this strategy. It risks sending a wrong message (as does the accompanying editorial8 ) and does not advance our understanding of how to manage the other subsets of patients with inducible ischemia, which is the clinically relevant question.
It is also unclear why revascularization in these subjects with inducible ischemia should have reduced the occurrence of myocardial infarction, because several studies, such as GISSI-2,9 have shown the inability of a positive postinfarction exercise test to predict reinfarction. In addition, less than half the conservatively treated patients were taking β-blocking agents after an infarction with inducible ischemia, hardly an indication of optimal therapy given the known benefits of these agents in reducing morbidity and mortality. Nor is there any indication about the use of lipid-lowering drugs, despite their well-established benefits in secondary prevention. Left ventricular function, an important postinfarction prognosticator, does not appear to have been characterized in the conservative-strategy group. Finally, the infarction rate related to angioplasty in the invasive-strategy group was surprisingly low at 0.8%, compared with the 8% to 15% generally reported.10
An opportunity was missed to perform a more satisfactory trial examining this interesting question. Such a trial would have posed the question not in terms of an invasive versus a conservative strategy but rather in terms of an invasive strategy versus the most optimal medical therapy, including β-blockers and lipid-lowering agents. Such a study would also have focused on subjects with inducible ischemia whose clinical management is presently uncertain (>5 METs exercise) and who ideally would have had a single identifiable culprit lesion on coronary arteriography. In the meantime, the findings of Madsen et al1 do not justify a blanket recommendation to revascularize all patients with inducible ischemia after myocardial infarction.
- Copyright © 1999 by American Heart Association
Madsen JK, Grande P, Saunamäki K, Thayssen P, Kassis E, Eriksen U, Rasmussen K, Haunsø S, Nielsen TT, Haghfelt T, Fritz-Hansen P, Hjelms E, Paulsen PK, Alstrup P, Arendrup H, Niebuhr-Jørgensen U, Andersen LI, on behalf of the DANAMI Study Group. Danish multicenter randomized study of invasive versus conservative treatment in patients with inducible ischemia after thrombolysis in acute myocardial infarction (DANAMI). Circulation. 1997;96:748–755.
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In reply to the comments made by Drs Bogaty and Dagenais, we would like to make the following remarks.
In our article, we suggest that all patients with inducible postinfarction ischemia should be “referred to coronary arteriography and revascularized accordingly” because this strategy resulted in the above-mentioned reduction in the incidence of acute myocardial infarction (AMI) and unstable angina.
We are preparing an analysis of cost benefit, but our primary aim was to evaluate the clinical effect; hence, the above conclusion.
Whether the results and conclusions are valid for all subgroups of patients is a general question for all intervention studies. We are preparing subanalysis of various subgroups, and so far, these results have not changed our overall conclusion.
There are, to the best of our knowledge, no controlled studies of high-risk post-AMI patients (other than the present study) that show a prognostic benefit of revascularization; hence, we do not see any ethical problem in randomizing such patients.
Drs Bogaty and Dagenais are surprised that we could show a difference, even though the patients were not a high-risk group. What the study shows is that postinfarction patients with ischemia constitute a proper group to select for procedures such as angiography, whether high risk or not.
In our article, we have already commented on the use of β-blockers. With regard to cholesterol-lowering treatment, the study was initiated before publication of the 4S study, but the effect on mortality will probably be found in both groups.
We still believe that our study gives scientific support for the widespread practice of catheterization of all postinfarction patients with ischemia, with subsequent revascularization.