"The chance of artery closure was reduced by 45 percent by the combined therapy," says senior researcher Freek W.A. Verheugt, M.D., Ph.D., director of cardiology at the Heartcenter of University Medical Center, The Netherlands. "This study shows that patients should use at least three months of oral anticoagulants plus aspirin after they have been treated with clot busters for a heart attack."
In some heart attacks, an electrocardiogram reveals ST-elevation, an indicator of heart damage often associated with a blood clot. Survival after an ST-elevation heart attack depends on how quickly coronary blood flow is restored. Recurrent heart attacks are often attributed to reocclusion, or closing up, of the artery originally involved in the heart attack. Physicians use antithrombotic drugs to prevent clots or fibrinolytic drugs to destroy clots. But arteries reocclude after the successful use of fibrinolytics in as many as 30 percent of patients within the first year, Verheugt says.
"In Europe, it is common to add oral anticoagulants to aspirin treatment in patients with clogged coronary arteries," he says.
Researchers hypothesized that the prolonged combination of aspirin and coumarin would be more effective than the standard treatment of aspirin alone. They identified 308 heart-attack patients participating in the Antithrombotics in the Prevention of Reocclusion in Coronary Thrombolysis (APRICOT)-2 study involving seven clinics in The Netherlands between 1994 and 2000. Within 48 hours after patients received clot-busting drug therapy, doctors tested patients' blood flow on the Thrombolysis in Myocardial Infarction (TIMI) scale, a measure of flow through the affected artery. Patients with a TIMI flow grade of 3, which meant their arteries were open, were eligible to participate. Participants were in their mid-40s to early 60s, and just over 80 percent were male.
A group of 123 patients took aspirin and a moderate dose of coumarin. In addition, they continued to take the antithrombotic drug heparin until moderate anticoagulation was achieved. This added as many as 66 additional hours of heparin treatment. A group of 128 control patients used only the daily dose of aspirin and had no additional heparin.
Researchers performed a follow-up angiography after three months. Reocclusion occurred in 15 percent of the combined group (19 patients) vs. 28 percent of the aspirin-only group (36 patients). Problem-free survival was also significantly higher in the combined group – 86 percent vs. 66 percent and they had a significantly lower incidence of a second heart attack – 2 percent vs. 8 percent.
One side effect of coumarin is a higher risk of bleeding. However, bleeding complications as defined by TIMI criteria occurred in only 5 percent (seven patients) of the combined group vs. 3 percent (four patients) in the aspirin-only group. The difference wasn't statistically significant.
"Since this therapy is rarely available in the United States, our study indicates that maybe newer and more easily applicable oral anticoagulants should also be tested," Verheugt says.
"This is the largest randomized study to date with both clinical and angiographic follow-up addressing the efficacy of a continuous, combined antithrombotic regimen up to three months after a ST-elevation heart attack. However, with respect to the implications for daily clinical practice, we will have to wait for the results of larger trials on this and other antithrombotic regimens."
Co-authors of the study include Marc A. Brouwer, M.D.; Paul J.P.C. van den Bergh, M.D.; Wim R.M. Aengevaeren, M.D., Ph.D.; Gerrit Veen, M.D., Ph.D.; Hans E. Luijten, M.D.; Don P. Hertzberger, M.D.; Ad J. van Boven, M.D., Ph.D.; Ralf P.J.W. Vromans, M.D.; and Gérard J.H. Uijen, Ph.D.
Bayer AG Germany funded part of the study.
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