American College of Cardiology

Study Raises Hopes for Preventing Blood Clots

(Jun. 1, 1999) A new study may help revive hopes for a class of drugs known as direct thrombin inhibitors. The study, appearing in the June issue of the Journal of the American College of Cardiology, shows that one of these drugs, known as argatroban (Novastan), may enhance the clot-dissolving properties of t-PA in heart attack patients.

Several years ago, cardiovascular researchers held great hopes for the direct thrombin inhibitors, which interrupt a key step in the blood-clotting process. But then several large trials showed that one of the drugs, hirudin, was no better than heparin—a long-established drug used for treating people with unstable angina—and hopes for the entire class of drugs began to fade.

In the MINT (Myocardial Infarction with Novastan and t-PA) study, 125 heart attack patients within six hours of the onset of symptoms were randomized to receive heparin, low-dose argatroban, or high-dose argatroban as an adjunct to the clot-buster t-PA. The rate of completely opened vessels, called the TIMI 3 flow rate, was 42.1 percent in the heparin group, 56.8 percent in the low-dose argatroban group, and 58.7 percent in the high-dose argatroban group, but this difference did not achieve statistical significance.

However, in the subset of patients who sought attention, more than three hours after the start of symptoms, the TIMI 3 flow rate was 20 percent in the heparin group, 50 percent in the low-dose argatroban group, and 57.1 percent in the high-dose argatroban group, a difference which did achieve statistical significance. Bleeding rates and major cardiac events also tended to occur less frequently in the argatroban groups.

"We believe that thrombin inhibitors aren't all the same," said Dr. Ik-Kyung Jang, of the Massachusetts General Hospital and Harvard Medical School in Boston. "There are clear differences between the agents, especially when it comes to the inhibition of clot-bound thrombin." Dr. Jang speculated that argatroban was especially effective in the older clots of patients who presented after three hours because it was able to inhibit the action of thrombin that had become incorporated in the mature clot.

"We shouldn't assume that since the hirudin studies were negative all studies with other direct thrombin inhibitors will be negative," said Dr. Jang.

The American College of Cardiology, a 24,000-member nonprofit professional medical society and teaching institution, is dedicated to fostering optimal cardiovascular care and disease prevention through professional education, promotion of research, leadership in the development of standards and guidelines, and the formulation of health care policy.

The American College of Cardiology (ACC) provides these news reports of clinical studies published in the Journal of the American College of Cardiology as a service to physicians, the media, the public, and other interested parties. However, statements or opinions expressed in these reports reflect the view of the author(s) and do not represent official policy of the ACC unless stated so.

Back to June Releases