Like many of the nation's heart specialists, Eugene Braunwald began the year convinced that an experimental drug he had been giving to heart attack victims was about to alter the course of American medicine.

For two years Braunwald, chairman of Harvard Medical School's department of medicine, had been using tissue plasminogen activator (TPA) to dissolve blood clots, the major cause of heart attacks. A cautious academic who has written some of the nation's leading texts on heart disease, Braunwald was elated by the drug's performance in trials he has directed for the National Institutes of Health.

"As a doctor, this is the most exciting thing to come along in my lifetime in medicine," he said. "Heart attacks cause 25 percent of the deaths in this country. We are talking about a drug that could save the lives of millions. Nothing I have ever seen offers more hope to the sick."

So when a committee advising the Food and Drug Administration rejected the drug at a lengthy, contentious meeting May 29, Braunwald was "flabbergasted, just shocked." The decision caused a furor in the medical and financial communities, and the FDA was besieged.

The Wall Street Journal's editorial board, which advocates lifting what it regards as unnecessary regulations, led the charge by saying that in seeking more data, the panel "decided to sacrifice thousands of American lives on an altar of pedantry."

Health experts, however, said that approving TPA without proof that it is safe at the recommended dosage would have been a crime.

"The information made available at that meeting was simply not sufficient to allow us to approve TPA," FDA Commissioner Frank E. Young said in an interview. "We are not really in a position to work on hunches. The American people have a right to know that when the FDA approves a drug, it is safe and effective."

The committee, acknowledging TPA's potential to dissolve clots, assailed reports presented by the drug's manufacturer, Genentech Inc., as incomplete and confusing. Questions emerged about the drug's safety and effectiveness, its proper dosage, its manufacturing process and the completeness of the company's test results. Genentech was told it would have to provide better results.

The FDA moved quickly to get more information, and a decision, possibly to approve the drug, is expected at any time. Still, the anger and confusion that accompanied the intitial decision underscores how little understood the FDA's procedures are, and it illustrates what can happen when a young company substitutes confidence and potential for facts and figures.

TPA was widely expected to be the first billion-dollar product to emerge from the growing biotechnology industry. Genentech had spent millions to develop it and was far ahead of its competitors. Analysts predicted that TPA would make the company a star.

If administered soon enough after the onset of a heart attack, the drug, a genetically engineered replica of a protein the body produces naturally, has proven astonishingly effective in melting the fatty clots that impede the flow of blood to the heart.

Heart attacks are the nation's leading killer; more than 400,000 Americans die of them each year. Chances of survival depend largely on the condition of the patient's heart. And that often is determined by how much muscle damage occurs when a clot interrupts normal blood flow.

Genentech had provided data to show that TPA opens clogged arteries in more than 65 percent of patients, which is twice the rate of another drug, streptokinase, that was approved for intravenous use May 29. Streptokinase, which has undergone lengthy trials that show it saves lives, offers potentially important benefits, such as lowering blood pressure and thinning blood, that TPA does not, even though streptokinase is not as effective at dissolving clots.

The support for TPA was mostly based on the following logic: How can you say no to a drug that opens clots at twice the rate as the drug you just approved?

But there was no specific data presented to show that opening clots prolongs lives. Panelists demanded to see how efficiently the heart could pump after the drug was used. And they were unhappy with data that suggested that high doses of TPA caused an unacceptable rate of bleeding in the brain.

"It is a difficult thing to say," Dr. Jeremy Ruskin, director of the cardiac arrhythmia service at Massachusetts General Hospital, said at the meeting. "But while my bias is that clot lysis {dissolving} is clearly a desirable goal, that it is probably the mechanism by which these drugs are effective, we don't know that. And I believe those data are not available."

"I think everyone just went into shock," said Dr. Eric Topol, a cardiologist at the University of Michigan who has treated hundreds of patients with TPA. "There is just no better way in medicine to get an artery open. This drug will have a tremendous impact on the nation. I think it is fair to compare it to penicillin."

The timing seemed perfect for the drug's approval. The FDA, at least in part out of recognition of the growing threat of AIDS, has recently moved aggressively to bring promising new drugs to market quickly.

TPA appeared to many as a wonder drug, and Genentech officials had placed ads in medical journals trumpeting its arrival. Company spokesmen have maintained official silence in the aftermath of the rejection, but privately they said the information they provided was all the FDA wanted to see. To many of those who attended the meeting, the committee appeared anxious to put the arrogant young team from Genentech in its place.

"These guys came in like cowboys," said one medical official who attended the meeting but is not connected with the approval process. "They were so sure of themselves they forgot that the committee held all the cards."

Committee members, many of them eminent cardiologists, have been stung by charges that anything other than science influenced the decision to require Genentech to produce more data. They say it would be unethical to permit a drug on the market with so many unresolved questions.

"People are attributing to the committee motives that just aren't there," said Dr. Craig Pratt, professor of medicine at the Baylor College of Medicine, and chairman of the Cardio-Renal Advisory Committee. "We care about making certain drugs are safe and effective before they are sold in the United States. We continue to believe TPA will be a promising drug, but we absolutely insist that the company provide data to show that it is safe. On May 29, they failed to do that."

The most disturbing information to surface at the May meeting was that a dose of 150 milligrams the drug caused so much bleeding that up to 4 percent of the patients had brain hemorrhages. The percentage has since proven to be much lower.

Doctors using the drug no longer administer 150 milligrams doses, having found that 100 milligrams is equally effective and much safer, with far fewer than one percent of patients suffering cerebral hemorrhage.

At the meeting in May, even though a great deal was riding on the presentation of facts, none of that was clear.

"If you studied the use of aspirin at four pills per dose, you would find the incidence of bleeding to be very high," said Dr. Burton Sobel, a noted cardiologist at Washington University in St. Louis and a consultant to Genentech. "That doesn't mean it's a bad drug. It just means that four pills on an empty stomach is a bad idea. Any drug when used in excess will cause toxicity. But only a few are capable of saving your life."