It was one of those findings that would change medicine, Dr. Christopher Lewandowski thought.

For years, doctors had tried — and failed — to find a treatment that would preserve the brains of stroke patients. The task was beginning to seem hopeless: Once a clot blocked a blood vessel supplying the brain, its cells quickly began to die.

But then a large federal clinical trial proved that a so-called clot-buster drug, tissue plasminogen activator (TPA), could prevent brain injury after a stroke by opening up the blocked vessel. Lewandowski, an emergency medicine physician in Detroit and the trial's principal investigator, said, "We felt the data was so strong we didn't have to explain it."

He was wrong. That groundbreaking clinical trial concluded 22 years ago, yet Lewandowski and others are still trying to explain the data to a powerful contingent of doubters. The skeptics teach medical students that TPA is dangerous, causing brain hemorrhages. Dr. Jerome Hoffman, an emergency medicine specialist, believes that while the initial trial and a second one were positive, both were flawed. Better to just let a stroke run its course, the skeptics say.

Close to 700,000 patients have strokes caused by blood clots each year and could be helped by TPA. Yet as many as 30 percent who arrive at hospitals in time and are perfect candidates for the clot-buster do not receive it. The result: paralysis and muscle weakness; impaired cognition, speech or vision; emotional and behavioral dysfunction; and other neurological injuries.

Stroke treatment guidelines issued by the American Heart Association and the American Stroke Association strongly endorse TPA for patients after they've been properly evaluated. But treatment must start within three hours (in some cases, 4½ hours) of the stroke's onset, and the sooner, the better.

A number of medical societies also endorse the treatment as highly effective in reducing disability. The drug can cause or exacerbate cerebral hemorrhage, or bleeding in the brain — a real risk. But in most stroke patients it prevents brain injury, and in any event, rates of cerebral hemorrhage have declined as doctors have gained experience over the years.

Without treatment, "many patients end up permanently disabled," said Dr. Gregg C. Fonarow, a cardiologist at the University of California, Los Angeles.

While the vocal disbelievers are a minority, it is increasingly easy for them to spread their message on social media. Dr. Charles R. Wira, a Yale professor, said that when he talked to residents about TPA, they often start citing blogs and podcasts. "They have not read the articles or practice guidelines."

For neurologists, the worst scenario by far is the patient who is never even asked if he or she wants the clot-buster. About a decade ago, Lewandowski got a call that his father had had a stroke. But his father had gotten to the hospital within 45 minutes.

Lewandowski told his mother to tell the emergency room doctor to give the clot-buster. The doctor refused. "I got in my car and drove 400 miles to the hospital," he recalled. But by the time he got there, the treatment window had closed. "I felt like I had let my dad down."