Recommendation that physicians be a little more cautious in deciding against tPA treatment

Although use of the clot-dissolving drug tissue plasminogen activator (tPA) has revolutionized the treatment of acute stroke patients, many of those who could receive the drug do not because their initial symptoms appear mild or improve soon after they arrive at the hospital.

Now a study from Massachusetts General Hospital (MGH) confirms previous observations that eligible patients who do not receive tPA face a significant risk of disability. The report will appear in the November issue of Stroke and is receiving early online release.

"Our primary finding was that about 30 percent of those patients judged 'too good to treat' either died or were discharged to a rehabilitation facility," says Eric Smith, MD, FRCPC, of MGH Neurology, the study's lead author. "Unfortunately we were not able to find any features that could predict which of the untreated patients would have problems."

When a stroke is caused by a blocked blood vessel, tPA can safely dissolve the clot if given within three hours of symptom onset, sometimes completely reversing the effects of the stroke. Many patients do not arrive at a hospital soon enough to receive the drug, but even when they do, physicians must weigh the small but significant risk that tPA treatment could cause a brain hemorrhage, a potentially devastating complication. Because of this risk, patients with less severe symptoms may not receive tPA in the hopes that they will get better on their own. An observation from an earlier study suggested that many of those patients would not do well and led to the current investigation.

The research team reviewed records on more than 400 patients with ischemic (clot-related) stroke that came to the MGH Emergency Department from 2002 to 2004. Of 128 patients who arrived within the three-hour safe treatment window, 71 did not receive tPA. More than half the untreated patients had been considered "too good to treat," primarily because their symptoms were stable and mild or improved rapidly. Out of those 41 patients, two died during their hospitalization and nine were discharged to a rehabilitation facility because of continuing neurological problems.

Smith explains that rapid symptom improvement seen early in the course of a stroke could reflect the affected area of the brain "borrowing" blood from nearby areas. But if the initial blockage affects the primary blood supply and is not removed, symptoms may eventually worsen.

"Right now we can only recommend that physicians be a little more cautious in deciding against tPA treatment," he adds. "We can suggest that more attention be paid to patients' ability to walk – something that often is not evaluated – since gait disturbance was a reason why several could not go home. But we really need to find ways to predict who will do poorly without tPA, and for that we'll need larger trials involving several institutions." Smith is an instructor in Neurology at Harvard Medical School.