Correspondence
Warfarin, Aspirin, or Both after Myocardial Infarction
N Engl J Med 2003; 348:256-257January 16, 2003
- Article
To the Editor:
Hurlen et al. (Sept. 26 issue)1 showed that warfarin with or without aspirin, as compared with aspirin alone, was associated with a reduction in the risk of the composite end point of death, nonfatal myocardial infarction, or embolic stroke in patients with myocardial infarction but did not establish its clinical relevance. They did not assess the implications of the components of the end point for patients. As compared with aspirin alone, the absolute reduction in the rate of nonfatal myocardial infarction with warfarin alone was 0.6 percent per year and with warfarin plus aspirin was 1.1 percent. Patients are not likely to accept long-term warfarin therapy for such a modest reduction in a nondisabling, nonfatal condition. A similar reduction in the rate of events such as death or stroke is more likely to lead to acceptance of warfarin therapy. Hurlen et al., however, found no reduction in mortality and found a reduction in the rate of stroke of 0.3 percent per year with both warfarin and warfarin plus aspirin — too small to change clinical practice.
1 ReferencesPatrick Pullicino, M.D., Ph.D.
New Jersey Medical School, Newark, NJ 07103-2714
pullic@umdnj.edu John L.P. Thompson, Ph.D.
Columbia University, New York, NY 10032-26031
Hurlen M ,Abdelnoor M ,Smith P ,Erikssen J ,Arnesen H . Warfarin, aspirin, or both after myocardial infarction. N Engl J Med 2002;347:969-974
Full Text | Web of Science | Medline
To the Editor:
Hurlen et al. found warfarin, alone or in combination with aspirin, to be superior to aspirin alone after acute myocardial infarction. Becker, in the accompanying editorial,1 concluded on the basis of this and another study (the Antithrombotics in the Prevention of Reocclusion in Coronary Thrombolysis 2 trial2) that anticoagulation therapy should be “strongly considered” after acute myocardial infarction.
We believe that the general applicability of the findings of these two trials is severely limited by the restricted use of coronary intervention. American College of Cardiology–American Heart Association guidelines3 recommend coronary angiography for patients with acute myocardial infarction associated with ST-segment elevation who have spontaneous or provocable ischemia and for most patients with acute myocardial infarction not associated with ST-segment elevation, who clearly benefit from an early, aggressive approach. The value of warfarin has been demonstrated in patients who, for the most part, do not undergo early coronary intervention. Conceivably, anticoagulation may be beneficial in patients who leave the hospital with severe narrowing of the infarct-related artery, but it may not be as beneficial in patients who are discharged after successful coronary intervention. We believe that the value of warfarin in patients who are treated according to current guidelines remains to be determined.
3 ReferencesGuy Amit, M.D.
Ruben Ilia, M.D.
Doron Zahger, M.D.
Soroka University Medical Center, 84101 Beer-Sheva, Israel
amitlaz@netvision.net. il 1
Becker RC . Antithrombotic therapy after myocardial infarction. N Engl J Med 2002;347:1019-1022
Full Text | Web of Science | Medline2
Brouwer MA ,van den Bergh PJ ,Aengevaeren WR , et al. Aspirin plus coumarin versus aspirin alone in the prevention of reocclusion after fibrinolysis for acute myocardial infarction: results of the Antithrombotics in the Prevention of Reocclusion In Coronary Thrombolysis (APRICOT)-2 Trial. Circulation 2002;106:659-665
CrossRef | Web of Science | Medline3
Ryan TJ ,Anderson JL ,Antman EM , et al. ACC/AHA guidelines for the management of patients with acute myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction). J Am Coll Cardiol 1996;28:1328-1428
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To the Editor:
Hurlen et al. do not report on the prevalence of atrial fibrillation in their patients with myocardial infarction after random assignment to treatment with aspirin, warfarin, or aspirin plus warfarin. These data need to be reported. In their patients with sinus rhythm, what were the incidence rates of death, reinfarction, and thromboembolic stroke in the three treatment groups?
Patients 75 years of age or older were excluded from the study. The mean age of the patients was 60 years. Because the efficacy and safety of cardiovascular drugs may differ between elderly patients and younger patients, it is important to enroll elderly patients in randomized, controlled trials so that physicians can provide evidence-based medical care to this high-risk population.
Wilbert S. Aronow, M.D.
New York Medical College, Valhalla, NY 10595
wsaronow@aol.com Author/Editor Response
The Warfarin, Aspirin, Reinfarction Study (WARIS II) showed that warfarin, alone or in combination with aspirin, was superior to aspirin alone in reducing the incidence of the composite end point of death, nonfatal reinfarction, or nonfatal thromboembolic stroke after acute myocardial infarction. Pullicino and Thompson question the clinical relevance of the findings for patients with nonfatal myocardial infarction. Nonfatal infarction may have serious implications clinically, socially, psychologically, and economically. Thus, we believe that a reduction in the incidence of nonfatal reinfarction is important. We agree, however, that there is a need to identify subgroups in which anticoagulant therapy may be either particularly beneficial or harmful.
Amit et al. argue that the applicability of the WARIS II trial results may be limited by the restricted use of acute percutaneous coronary interventions. The rationale for long-term antithrombotic therapy after acute myocardial infarction does not vary according to whether or not patients have had initial percutaneous coronary interventions. A recent study involving the use of intracoronary ultrasonography demonstrated multiple ruptured plaques in addition to the culprit lesion in patients with acute coronary syndromes.1 Thus, atherosclerotic disease associated with the risk of thrombotic complications extends beyond the culprit lesion responsible for a single acute clinical episode in most patients.
Aronow raises the issue of patients with atrial fibrillation. Patients with paroxysmal, persistent, or permanent atrial fibrillation at the time of randomization were considered to have an indication for warfarin therapy. Hence, they were ineligible for the study. Exceptions were made for patients 60 years of age or younger who did not have conventional risk factors and who had structurally normal hearts. In general, it is important to enroll elderly patients in studies. However, we believe that the increased risk of bleeding associated with older age may limit the number of elderly patients who will eventually take warfarin in this context.
1 ReferencesMette Hurlen, M.D.
Harald Arnesen, M.D., Ph.D.
Ullevål University Hospital, N-0407 Oslo, NorwayPål Smith, M.D., Ph.D.
Bærum Hospital, N-1306 Bærum, Norway1
Rioufol G ,Finet G ,Ginon I , et al. Multiple atherosclerotic plaque rupture in acute coronary syndrome: a three-vessel intravascular ultrasound study. Circulation 2002;106:804-808
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