The ExTRACT-TIMI 25 trial compared a strategy using enoxaparin, a type of low-molecular-weight heparin, to a strategy using unfractionated heparin as adjunctive therapy in patients whose primary treatment for heart attack, or myocardial infarction (MI), was clot-busting medication, known as fibrinolytic drugs. Both unfractionated heparin and enoxaparin inhibit thrombin, a blood protein that plays a key role in the formation of new blood clots. However, unfractionated heparin is delivered by intravenous infusion, while enoxaparin can simply be injected under the skin. Enoxaparin also appears to have more powerful anti-clotting effects by more effectively blocking the clotting mechanism at an earlier stage than unfractionated heparin.
"Our study provides compelling evidence that the enoxaparin strategy is superior to the standard unfractionated heparin strategy as antithrombin therapy to support fibrinolytic therapy," said Dr. Elliott Antman, M.D., a professor of medicine at Harvard Medical School, Boston, and the Principal Investigator of the Enoxaprin and Thrombosis Reperfusion for Acute Myocardial Infarction Treatment: Thrombosis in Myocardial Infraction. (ExTRACT-TIMI 25) study led by the TIMI Study Group (Boston).
"Based on the results of the ExTRACT-TIMI 25 trial, we believe that a strategy using enoxaparin is now the preferred anticoagulant regimen in heart attack patients who receive clot-busting drugs," said Eugene Braunwald, M.D., M.A.C.C., Distinguished Hersey Professor of Medicine, Harvard Medical School, Chairman, TIMI Study Group, Brigham and Women's Hospital.
Researchers found that enoxaparin reduced the combined risk of death and MI within 30 days by 17 percent. Similarly, enoxaparin reduced the 30-day risk of nonfatal repeat MI by 33 percent, and the 30-day combined risk of death, nonfatal MI, and urgent need to re-establish blood flow to the heart by 19 percent. All of the findings were highly statistically significant.
The trial enrolled 20,506 patients from 674 medical centers in 48 countries. All patients had ST-elevation MI (STEMI), a serious form of heart attack characterized by elevation of the "ST segment" on the electrocardiogram. They were treated with a fibrinolytic, or clot-busting, medication within six hours of first experiencing chest pain, and were then randomly assigned to receive therapy with enoxaparin or unfractionated heparin.
To make sure there was no unintended bias in interpreting the results, the trial used a double-blind, double-dummy design: study participants received both intravenous infusions and twice-daily injections without the physician or the patient knowing which contained the study medication and which was the placebo.
The rates of serious bleeding were lower overall than reported in prior trials. Patients who were treated with the enoxaparin strategy were more likely to experience major bleeding. However, when researchers calculated net clinical benefit, which takes into account both effectiveness and safety, the enoxaparin strategy was, on balance, associated with significantly better outcomes.
The study has critical importance for the treatment of most patients who suffer an MI, Dr. Antman said. Although opening a blocked coronary artery with a balloon-tipped catheter, or percutaneous coronary intervention (PCI), has been shown to be an the most effective treatment for MI in specialized centers, the vast majority of patients worldwide receive clot-busting medications to treat their heart attack.
"The availability of PCI is still quite limited in most parts of the world, and even in large parts of the United States it is impossible to get a patient with acute MI to the catheterization laboratory in a timely fashion," said Dr. Antman. "Fibrinolysis is the most common treatment for ST-elevation MI worldwide, and this study shows that the new strategy using enoxaparin is clearly preferable for enhancing that form of treatment for STEMI patients."
Dr. Antman will present the results of the ExTRACT-TIMI 25 study at a Late Breaking Clinical Trials session on Tuesday, March 14, at 2:15 p.m.
The American College of Cardiology (www.acc.org) represents the majority of board certified cardiovascular physicians in the United States. Its mission is to advocate for quality cardiovascular care through education, research, promotion, development and application of standards and guidelines- and to influence health care policy. ACC.06 and the ACC inaugural i2 Summit, the first-ever meeting for interventional cardiologists, will bring together more than 30,000 cardiologists and cardiovascular specialists to share the newest discoveries in treatment and prevention, while helping the ACC achieve its mission to address and improve issues in cardiovascular medicine.
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