Correspondence
Management of Non–Q-Wave Myocardial Infarction
N Engl J Med 1998; 339:1395-1398November 5, 1998
- Article
To the Editor:
The report by Boden et al. (June 18 issue)1 on the outcomes of patients with acute non–Q-wave myocardial infarction (the Veterans Affairs Non–Q-Wave Infarction Strategies in Hospital [VANQWISH] trial) is a welcome and important addition to our understanding of the care of this group of patients whose treatment and prognosis have been controversial.2
Although the authors are successful in their attempt to answer the question whether we are doing too much in the way of invasive therapy for non–Q-wave myocardial infarction, it would be helpful for them to comment on certain aspects of their results that suggest that we may not be doing enough in the way of conservative therapy.
Before randomization, only 22.5 percent of the patients who were assigned to the conservative strategy were taking a beta-blocker, and less than half (45 percent) were taking aspirin. Similarly, at the time of discharge, only 52 percent of patients were taking beta-blockers, and 89 percent were taking aspirin. More intensive use of these medications might have further improved the outcomes in the group that received conservative therapy.
Were there attempts to modify risk factors (for example, 46 percent of patients smoked at entry)? Trials of statins have demonstrated as much as a 40 percent reduction in secondary events after acute myocardial infarction, even in patients with “normal” lipid profiles.3,4 Information about the subsequent control of risk factors would have made our understanding of the outcomes at one year more meaningful. In addition, the absence of such information lends further support to the perception that in reality, “doing everything” (to satisfy the courts, the consumers, and the doctors' finances) may inevitably mean doing something invasive.
Boden et al. are careful to note the limitations of the study, but they fail to mention the possible effect of late stratification (up to three days after myocardial infarction). In the case of conservative therapy, early use of drugs may have a critical effect on outcomes.5,6
6 ReferencesSusanna E. Bedell, M.D.
Thomas B. Graboys, M.D.
Shmuel Ravid, M.D.
Brigham and Women's Hospital, Boston, MA 021151
Boden WE ,O'Rourke RA ,Crawford MH , et al. Outcomes in patients with acute non-Q-wave myocardial infarction randomly assigned to an invasive as compared with a conservative management strategy. N Engl J Med 1998;338:1785-1792
Full Text | Web of Science | Medline2
Boden WE ,Roberts R . Prognosis and management of patients with non-Q-wave myocardial infarction. Prog Cardiol 1991;4:143-1603
The Scandinavian Simvastatin Survival Study Group
Web of Science | Medline4
Sacks FM ,Pfeffer MA ,Moye LA , et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med 1996;335:1001-1009
Full Text | Web of Science | Medline5
The Antiplatelet Trialists' Collaboration
CrossRef | Web of Science6
Warnica JW. Pharmacologic management of acute myocardial infarction. In: Gersh BJ, Rahimtoola SH, eds. Acute myocardial infarction. New York: Elsevier, 1991:205-17.
To the Editor:
The authors of the VANQWISH study and Lange and Hillis in their accompanying editorial1 conclude that routine early invasive treatment of patients with acute non–Q-wave myocardial infarction is not beneficial. When the results of the study were presented at the Scientific Sessions of the American Heart Association in November 1997, there was considerable discussion regarding the surprisingly poor outcome of patients who were assigned to the invasive strategy and who underwent coronary angiography but not revascularization. This finding was not discussed at all in the article, yet it bears heavily on the way in which this study should be interpreted and whether the results can be applied to patients in hospitals other than Veterans Affairs hospitals.
In the invasive-treatment group, only 44 percent of patients underwent revascularization. According to American practices, this rate is surprisingly low for a population of patients at moderate to high risk who have sustained a non–Q-wave myocardial infarction. Also, among the 238 patients in the invasive-strategy group who underwent angiography but not revascularization, the rate of death or nonfatal myocardial infarction at one year was 24 percent, and among the 20 patients who did not undergo angiography, it was 45 percent, as compared with a rate of 18 percent among patients in the invasive-treatment group who underwent revascularization. In addition, at one year, 40 of the 61 deaths in the invasive-treatment group were among patients who did not undergo revascularization.
These findings suggest that the physicians who participated in the trial were excessively conservative in offering revascularization to patients in the invasive-treatment group. They seemed to have been less reluctant to offer revascularization if patients had ischemia on exercise testing, as was mandated by the protocol of the conservative strategy. The patients in the invasive-treatment group did not undergo routine exercise testing. I would conclude that in this study, the absence of either revascularization or a prognostically useful exercise test results in a poor outcome after non–Q-wave myocardial infarction.
I would also conclude that the results of the study may not be applicable to other U.S. hospitals whose revascularization rates are higher than those of the Veterans Affairs hospitals that participated in the study.
1 ReferencesRandall C. Thompson, M.D.
University of Missouri, Kansas City, MO 641101
Lange RA ,Hillis LD . Use and overuse of angiography and revascularization for acute coronary syndromes. N Engl J Med 1998;338:1838-1839
Full Text | Web of Science | Medline
To the Editor:
In the study by Boden et al., an early invasive strategy of coronary angiography and revascularization for patients with non–Q-wave myocardial infarction was associated with an increase in early mortality. We believe the authors' conclusion that an early strategy of conservative management is preferable may not be fully justified for three main reasons.
First, longer-term survival results are needed to determine the net benefit of either revascularization strategy. Patients are referred for coronary-artery bypass grafting (CABG) despite the higher risk of early death, myocardial infarction, and stroke with CABG as compared with percutaneous revascularization, because there is a long-term (>10 years) survival benefit for certain subgroups of high-risk patients.1 Since the survival curves in the VANQWISH study appear to be converging by the end of the follow-up period (1000 days), there are insufficient data to conclude that long-term survival is improved with a conservative-management strategy.
Second, the mortality rate among patients who were treated with early surgical revascularization was unacceptably high. The 30-day mortality rate among patients in the early-invasive-treatment group who underwent CABG was 11.6 percent, which is nearly four times as high as the 3.2 percent early mortality rate for the combined results of the early CABG trials of the 1970s and early 1980s.1 Since high-risk patients with recurrent ischemia or heart failure were excluded from enrollment, we do not believe that the high-risk characteristics of the patients in the VANQWISH trial can explain the dramatically increased surgical mortality rate.
Third, the study was performed before the introduction of platelet glycoprotein IIb/IIIa inhibitors. All placebo-controlled interventional trials of glycoprotein IIb/IIIa inhibitors to date have shown an important and consistent reduction in death and myocardial infarction after percutaneous coronary intervention. Furthermore, in patients with acute coronary syndromes who underwent percutaneous revascularization, the long-term benefit was enhanced by the use of glycoprotein IIb/IIIa inhibitors for platelet blockade.2,3
Although we agree that further investigation is needed to determine the optimal role of angiography and revascularization in the care of patients with unstable angina and myocardial infarction without ST-segment elevation, the results of the VANQWISH trial are unfortunately inconclusive and should not be used to limit the use of angiography in patients with acute coronary syndromes.4
4 ReferencesMatthew T. Roe, M.D.
T. Eric Bowen, M.D.
Eric J. Topol, M.D.
Cleveland Clinic Foundation, Cleveland, OH 441951
Yusuf S ,Zucker D ,Peduzzi P , et al. Effect of coronary artery bypass graft surgery on survival: overview of 10-year results from randomised trials by the Coronary Artery Bypass Graft Surgery Trialists Collaboration. Lancet 1994;344:563-570[Erratum, Lancet 1994;344:1446.]
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Topol EJ ,Ferguson JJ ,Weisman HF , et al. Long-term protection from myocardial ischemic events in a randomized trial of brief integrin beta-3 blockade with percutaneous coronary intervention. JAMA 1997;278:479-484
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Lincoff AM ,Califf RM ,Anderson KM , et al. Evidence for prevention of death and myocardial infarction with platelet membrane glycoprotein IIb/IIIa receptor blockade by abciximab (c7E3 Fab) among patients with unstable angina undergoing percutaneous coronary revascularization. J Am Coll Cardiol 1997;30:149-156
CrossRef | Web of Science | Medline4
Lange RA ,Hillis LD . Use and overuse of angiography and revascularization for acute coronary syndromes. N Engl J Med 1998;338:1838-1839
Full Text | Web of Science | Medline
To the Editor:
In the VANQWISH trial, Boden et al. found no evidence that the clinical outcomes of patients with non–Q-wave myocardial infarction are improved by a routine strategy of early invasive treatment (coronary angiography followed by percutaneous transluminal coronary angiography or CABG). We would like to comment on these findings.
The absence of Q waves on the electrocardiogram is a poor indicator of the presence of ischemia or residual myocardial-tissue viability.1 The viability of tissue, however, is of critical importance for the clinical prognosis of patients after acute myocardial infarction. It was shown in long-term follow-up studies that patients with residual tissue viability after infarction, as determined by nuclear imaging studies, have a high risk of cardiac complications if treated medically.2-4 In contrast, patients without evidence of viable tissue do well with medical therapy if cardiac function is not severely impaired.
We believe that many patients in the VANQWISH trial had relatively small areas of necrosis (subendocardial scarring) and good overall left ventricular function (ejection fraction, 50 to 53 percent), which may explain the increased risk of invasive procedures in these patients, since no benefit can be expected from such procedures. In the trial there was a relatively high mortality rate in the first week after CABG.
The authors do not describe the thallium-201 procedure that was used to assess the presence of ischemia or residual tissue viability. Was a reinjection protocol used?
4 ReferencesJohannes M. Huitink, M.D., Ph.D.
Academic Medical Center, 1105 AZ Amsterdam, the NetherlandsJeroen J. Bax, M.D., Ph.D.
Leiden University Medical Center, 2333 AA Leiden, the Netherlands1
Hashimoto T ,Kambara H ,Fudo T , et al. Non-Q wave versus Q wave myocardial infarction: regional myocardial metabolism and blood flow assessed by positron emission tomography. J Am Coll Cardiol 1988;12:88-93
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Yoshida K ,Gould KL . Quantitative relation of myocardial infarct size and myocardial viability by positron emission tomography to left ventricular ejection fraction and 3-year mortality with and without revascularization. J Am Coll Cardiol 1993;22:984-997
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Basu S ,Senior R ,Raval U ,Lahiri A . Superiority of nitrate-enhanced 201Tl over conventional redistribution 201Tl imaging for prognostic evaluation after myocardial infarction and thrombolysis. Circulation 1997;96:2932-2937
Web of Science | Medline4
Huitink JM ,Visser FC ,Bax JJ , et al. Predictive value of planar 18F-fluorodeoxyglucose imaging for cardiac events in patients after acute myocardial infarction. Am J Cardiol 1998;81:1072-1077
CrossRef | Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: We agree with Bedell et al. that medical therapy after discharge was underused according to current guidelines and that more-intensive drug therapy and lifestyle changes might have resulted in even better clinical outcomes in the conservative-strategy group. Randomization up to 72 hours after infarction did not preclude the use of appropriate pharmacologic therapy earlier, and physicians were free to follow standard practice.
Dr. Thompson's claim that our results cannot “be applied to patients in hospitals other than Veterans Affairs hospitals” or to “hospitals whose revascularization rates are higher than those of the Veterans Affairs hospitals that participated in the study” is at variance with the fact that as Lange and Hillis noted in their editorial, no published, randomized trials have demonstrated the clear superiority of an invasive approach over a conservative approach. Dr. Thompson's assertion that our 44 percent rate of revascularization for non–Q-wave infarction “is surprisingly low” by American standards likewise contradicts results from three recently published trials of platelet glycoprotein IIb/IIIa inhibitors,1-3 undertaken in patients similar to ours who had unstable angina or non–Q-wave infarction, which reported rates of revascularization of 39, 44, and 38 percent. Thus, VANQWISH investigators were not “excessively conservative in offering revascularization.” Although event rates at one year among patients who underwent revascularization in the invasive-strategy group (18 percent) and the conservative-strategy group (15 percent) were somewhat lower than those in patients who underwent coronary angiography without revascularization (25 percent and 23 percent, respectively), it does not follow that the absence of revascularization “results in a poor outcome after non–Q-wave myocardial infarction.” Decisions to perform revascularization were left to the discretion of the investigators; distal coronary anatomy and coexisting conditions certainly influenced the clinical decisions. Since thallium stress testing was permitted at the discretion of the physicians in the invasive-treatment group, routine perfusion imaging in this group probably would not have increased revascularization rates.
Roe et al. suggest that our study provides “insufficient data to conclude that long-term survival is improved” by conservative management and point out the convergence of the Kaplan–Meier curves for the primary end point at the end of 44 months of follow-up. Nevertheless, during the period when most recurrent events occur (within the first year), there was a clear benefit of conservative strategy. Also, the “unacceptably high” 30-day mortality rate among patients in the invasive-strategy group who underwent CABG within 8 days after acute myocardial infarction must be expected to differ from the much lower death rates among patients in earlier clinical trials who underwent elective CABG for stable coronary disease. In fact, in-hospital mortality among patients who undergo early CABG after acute infarction may be even higher than what we encountered.4
The trial was conducted before the use of glycoprotein IIb/IIIa inhibitors, which might have enhanced the outcome with either strategy. Finally, the intent of the trial was to assess the need for routine angiography in all patients with non–Q-wave infarction, particularly those with uncomplicated cases or those without evidence of inducible ischemia; 52 percent of the patients in the conservative-strategy group did not require angiography during long-term follow-up, yet the death rate was only 1 percent at 30 days and 6 percent at 1 year.
We agree with Drs. Huitink and Bax that myocardial viability is a crucial determinant of the prognosis after myocardial infarction. Our use of symptom-limited thallium perfusion scintigraphy to elicit inducible ischemia before hospital discharge guided clinical decision making, but systematic studies of tissue viability were not part of the protocol.
4 ReferencesWilliam E. Boden, M.D.
State University of New York Health Science Center, Syracuse, NY 13210Robert A. O'Rourke, M.D.
University of Texas Health Science Center at San Antonio, San Antonio, TX 78284Michael H. Crawford, M.D.
University of New Mexico Health Science Center, Albuquerque, NM 871311
The Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) Study Investigators
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The Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) Study Investigators
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The PURSUIT Trial Investigators. Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes.N Engl J Med 1998;339:436-43.
4
Tu JV ,Sykora K ,Naylor CD . Assessing the outcomes of coronary artery bypass graft surgery: how many risk factors are enough? J Am Coll Cardiol 1997;30:1317-1323
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