Correspondence
Optimal Oral Anticoagulation for Patients with Nonrheumatic Atrial Fibrillation and Recent Cerebral Ischemia
N Engl J Med 1995; 333:1504November 30, 1995
- Article
To the Editor:
The European Atrial Fibrillation Trial demonstrated the efficacy of anticoagulant therapy in preventing stroke in high-risk patients with atrial fibrillation.1 The results were convincing because the number of events among untreated patients was large and the number of events among those treated with anticoagulants was small. Further analysis of the small group of events occurring among patients in the trial who were treated with anticoagulants can provide only a preliminary step toward the critical goal of specifying precisely the optimal range of anticoagulation for atrial fibrillation.
Strong evidence that low intensities of anticoagulation are effective has facilitated the more widespread and presumably safer use of anticoagulants in patients with atrial fibrillation.2 Investigators and clinicians want to know the lowest intensity of anticoagulation that effectively prevents stroke in these patients. In the study reported in the July 6 issue of the Journal, 3 the European Atrial Fibrillation Trial Study Group analyzed a total of 25 events categorized as ischemic. These included only 11 strokes and 2 other systemic embolic events. The remaining ischemic events, including 5 sudden deaths and 3 deaths due to congestive heart failure, were probably not due to thromboembolism. Indeed, the accompanying paper by Cannegieter et al.,4 which analyzed anticoagulant intensity and outcome in patients with mechanical heart valves, used much more specific definitions of thromboembolic events.
The investigators of the European Atrial Fibrillation Trial conclude that international normalized ratios (INRs) under 2.0 confer no protection against thromboembolism on patients with atrial fibrillation who have already had a stroke. The empirical basis for this conclusion is limited: seven “ischemic” events at INRs below 2.0 during a total of 40 person-years of observation. More important, this lowest category of INRs is too broad, lumping patients with values at or near 1.0 with patients whose values reflect measurable but low levels of anticoagulation — for example, those with ratios between 1.5 and 2.0.
The European Atrial Fibrillation Trial contributed greatly to our current awareness that embolic stroke in atrial fibrillation is preventable. However, we need much larger observational and randomized studies of patients treated with anticoagulants to define precisely the intensity of anticoagulation that minimizes the risks of both embolic and hemorrhagic events in the major categories of patients with atrial fibrillation.
4 ReferencesDaniel E. Singer, M.D.
Elaine M. Hylek, M.D., M.P.H.
Massachusetts General Hospital, Boston, MA 021141
EAFT (European Atrial Fibrillation Trial) Study Group
Web of Science | Medline2
Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation: analysis of pooled data from five randomized controlled trialsArch Intern Med 1994;154:1449-1457
CrossRef | Web of Science | Medline3
The European Atrial Fibrillation Trial Study Group
Full Text | Web of Science | Medline4
Cannegieter SC ,Rosendaal FR ,Wintzen AR ,van der Meer FJM ,Vandenbroucke JP ,Briet E . Optimal oral anticoagulant therapy in patients with mechanical heart valves. N Engl J Med 1995;333:11-17
Full Text | Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: Throughout our paper, we stressed the points that the number of observations in our study was small, that the results are not definitive, and that one should use caution in extrapolating our findings to primary prevention in atrial fibrillation. We agree completely with Drs. Singer and Hylek that more studies are needed to define the optimal range in patients with atrial fibrillation. Because of the limited number of events, we were unable to study accurately additional subgroups, such as various categories of patients with INRs under 2.0. As mentioned in our paper, two ongoing primary prevention studies are comparing various targets of anticoagulation and will provide more information in the near future. Regarding the definition of ischemic events in our study, we deliberately chose to include major cardiac events, since from the patient's perspective the prevention of ischemic heart disease and the prevention of stroke are equally important. We agree that cardiac events are etiologically heterogeneous, but so are strokes. Furthermore, the results of the study of Cannegieter et al., in which more restricted definitions of thromboembolic events were used, are strikingly similar to ours. In their study of patients with mechanical heart valves, the vast majority of ischemic events occurred at INR intensities under 2.5.
Peter J. Koudstaal, M.D.
University Hospital Rotterdam, 3015 GD Rotterdam, the NetherlandsAle Algra, M.D.
Jan van Gijn, M.D.
University Hospital Utrecht, 3584 CX Utrecht, the Netherlands- Citing Articles (6)
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