Clot-dissolving drugs minimize permanent damage to heart attack patients, a Harvard University researcher reported at the American College of Cardiology's annual meeting in Atlanta Monday. These drugs work so well that the National Heart, Lung and Blood Institute (NHLBI) is revising plans for a major study and will now give one of the drugs to all participants.

The study, Thrombolysis in Myocardial Infarction (TIMI), is an ongoing project that begins phase two "in the next two to three days at 25 medical centers in the United States," said Dr. Eugene Braunwald, chief of medicine at Harvard University Medical School and director of the study's second phase. Some 4,000 heart attack patients will be studied during the next two years.

Based on striking results of preliminary NHLBI studies over the past 1 1/2 years, all TIMI participants will receive a clot-dissolving drug known as tissue plasminogen activator, or TPA. Originally, half were scheduled to receive TPA and half were to be given a placebo. Now, researchers plan to give half of the patients TPA alone, while the other half will receive TPA and then undergo balloon angioplasty -- opening a clogged artery with a small balloon.

TPA is a naturally occurring substance in the body's blood clotting system. It can be mass produced using recombinant DNA techniques. TPA is one of a growing number of experimental drugs able to break up clots that obstruct coronary arteries, reduce blood flow and oxygen to heart cells and lead to heart attacks.

Another clot-dissolving drug, streptokinase, is also effective and has been used experimentally for about 25 years. In a study of some 12,000 patients, Italian researchers reported recently in the British Journal Lancet, streptokinase reduced deaths by about 20 percent.

When researchers compared TPA and streptokinase, they found TPA to be superior. TPA dissolved clots in 62 percent of patients, while streptokinase was effective, Braunwald said, in 31 percent. A newly developed type of TPA cleared clots from arteries in about 75 percent of patients.

For the best result, all clot-dissolving drugs must be used within four to six hours of a heart attack. The more quickly they are used, the less the damage to the heart.