New ideas in fighting clots, heart attacks.

New ideas in fighting clots, heart attacks

Almost every heart attack is associated with a narrowed coronary artery and a clot to block it. Researchers see promise in a number of clot-dissolving substances, particularly the up-and-coming recombinant tissue plasminogen activator (r-tPA). But none remedies the underlying problem--the narrowing of the artery--that sets the stage for a clot.

Now, researchers are studying several therapies that, when combined with r-tPA, may not only clear the clot but also prevent a recurrence. These were described earlier this month at the annual meeting of the American Federation for Clinical Research in Washington, D.C.

The strategy closest to clinical application adapts a technique now used for chronic, heart-related chest pain. In coronary angioplasty, a balloon-tipped catheter is threaded into an artery to a point of obstruction and inflated to push the vessel open (SN:11/29/80, p. 341). Researchers at the University of Michigan in Ann Arbor have compared the use of r-tPA alone with the use of r-tPA combined with coronary angioplasty.

In patients receiving r-tPA alone, the affected arteries were up to 75 to 80 percent narrower than normal after treatment. Patients getting the combined treatments showed only half that narrowing, and clot recurrence in that group was greatly reduced as well. Measurements of cardiac function after treatment showed that immediately widening the artery allowed the starved area of the heart to recover function, while after clot-dissolving treatment alone there was no recovery in the affected area. "I think all of us would agree that coronary angioplasty has a role [in treating victims of heart attacks],' says Eric Topol, who presented the study. But, he adds, adjustments in the r-tPA dose regimen could mean "it won't always have to be done on an emergency basis.'

Even after the combination of angioplasty and r-tPA, two of the eight patients in that treatment group had a recurrence of the clot. But another technique, in an early stage of research, may short-circuit such a clotting reaction, which can occur where arteries are unhealthily narrowed. As part of the normal repair process, platelets adhere to the walls of a vessel wherever there are breaks. But when the vessel is narrowed and coated with deposits, adhering platelets can clump and start to obstruct the blood flow. A monoclonal antiplatelet antibody, developed by researchers at Massachusetts General Hospital in Boston and the State University of New York at Stony Brook (SUNY), binds to a receptor on the platelet and blocks a necessary step in that clotting process. In the study (on dogs), the antibody did not appear to affect the ability of the platelets to adhere to vessel walls--and therefore caused no excess bleeding.

In an optimistic scenario, Barry Coller of SUNY speculates that r-tPA could someday be combined with the antiplatelet antibody to prevent an immediate recurrence of the clot. Once the patient is stabilized, angioplasty might be used to widen the artery. Researchers would then be left "merely' to deal with the question of why the artery narrowed in the first place--and how to prevent it from narrowing again.