Aspirin Plus Warfarin May Prevent Reocclusion.
Two new Dutch multicenter randomized trials of long-term warfarin in patients with an MI or unstable angina drew favorable attention at the 22nd Congress of the European Society of Cardiology.
In the second Antithrombotics in the Prevention of Reocclusion in Coronary Thrombolysis (APRICOT-2) study, 308 patients were randomized to the standard 80 mg/day of aspirin or to aspirin plus medium-intensity warfarin following successful thrombolysis for acute MI.
The goal was to see if the combination of aspirin and warfarin titrated to a target international normalized ratio (INR) of 2.0-3.0 would reduce the reocclusion rate in the infarct-related artery. Reocclusion occurs in 25%-35% of patients within 1 year after successful thrombolytic therapy for acute MI, despite use of aspirin, and increases the risk of reinfarction and mortality.
And, even in the absence of reinfarction, reocclusion inhibits recovery of left ventricular function, explained Dr. Michael A. Brouwer of University Medical Center, Nijmegen, the Netherlands.
In APRICOT-2, reocclusion (TIMI grade 2 or lesser blood flow) was present in 30% of patients on aspirin, compared with 18% on aspirin plus warfarin at follow-up angioplasty 3 months post-MI.
A totally occluded infarct-related artery was seen in 19% of aspirin-treated patients and 9% of those on combination therapy. Of patients on combination therapy, 83% survived free of reinfarction or a revascularization procedure.
Of those on aspirin alone, 70% survived. These differences were statistically significant.
The other major warfarin trial presented at the European congress was the second Antithrombotics in the Secondary Prevention of Events in Coronary Thrombosis (ASPECT-2) study.
This open-label, randomized trial was sponsored by the Netherlands Heart Foundation and was conducted at 60 Dutch hospitals. Nearly 1,000 patients with acute MI (87%) or unstable angina (13%) were randomized to receive 80 mg/day of aspirin, 80 mg/day of aspirin plus warfarin titrated to an INR of 2.0-2.5, or high-intensity warfarin alone to an INR of 3.0-4.0.
After a mean follow-up of 1 year, the rate of the primary study end point--a combination of all-cause mortality, MI, or stroke--was 9% in the aspirin-only group, compared with 5% with aspirin plus moderate-intensity warfarin. That's a 45% decrease in relative risk favoring the combination therapy.
"That means if 25 patients received aspirin plus coumadin for 1 year, one major event would be avoided," said Dr. Robert F. van Es of University Medical Center, Rotterdam, the Netherlands.
The primary end point rate in the high-intensity warfarin group was slightly over 5%, representing a 43% reduction in risk, compared with aspirin alone. Of patients on high-intensity warfarin, 1.2% died, vs. 4.5% mortality with aspirin.
The safety profile for oral anticoagulation was quite acceptable, Dr. van Es reported. Major bleeding was uncommon in all three treatment arms. The rate was 0.9 cases/100 patient-years with aspirin or high-intensity warfarin alone, and 2.1 cases/100 patient-years with aspirin plus warfarin. Combination therapy entailed a threefold increased rate of minor bleeding, compared with aspirin monotherapy. One fatal intracranial hemorrhage occurred with combination therapy.
Session cochair Dr. Frans Van de Werf, professor of cardiology at the University of Leuven (Belgium) observed that the impressive Dutch multicenter trials coupled with the negative results for abciximab in the large Global Utilization of Strategies to Open Occluded Arteries in Acute Coronary Syndromes (GUSTO-IV-ACS) trial are causing a shift in enthusiasm away from glycoprotein IIb/IIIa inhibitors in favor of anticoagulation in the setting of acute coronary syndromes not headed for early revascularization.
Skeptics noted that the Netherlands, as well as Scandinavia, Germany, and Switzerland, is a "coumadin-friendly" country. Anticoagulation is skillfully practiced there with the aid of centralized monitoring systems.
INR targets are far more frequently over- and undershot in other parts of the world, where it may not make sense to routinely employ long-term warfain in cases of acute coronary syndromes.
Dr. Freek W.A. Verheugt, professor of cardiology at University Hospital, Nijmegen, and an investigator in both trials, replied that the near future likely will bring routine daily self-monitoring of INRs.
"Each day the patient takes one drop of blood from himself or herself, puts it in a machine, and gets an INR reading. Insurers won't reimburse for it so far, but you can see the parallel to self-control in type 1 diabetes," he said at the conference.
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|Comment:||Aspirin Plus Warfarin May Prevent Reocclusion.|
|Publication:||Family Practice News|
|Date:||Oct 15, 2000|
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