Time waits for no man

After four hours the clock runs out for treatment benefits in stroke. Research confirms that rapid use of thrombolytics spells better outcomes.

By Brian Hoyle

Physicians have known for almost a decade now that early treatment with clot-busting thrombolytics improves a patient's chances for a full recovery after a stroke. In Canada these drugs are used extensively. Stroke patients who meet the criteria receive thrombolytics anywhere from 70% to 86% of the time, depending on their age.

A new study published in the March 6 issue of The Lancet outlines the importance of rapid treatment and gives more precise detail about when the treatment should be administered. The study analyzed the results of six controlled clinical trials involving 2,775 patients who were mostly in their late 60s. The results confirm, as expected, that rapid thrombolytic use following a stroke increases the chances of a positive three-month outcome.

The data came from three study groups � the Alteplase ThromboLysis for Acute Non-interventional Therapy in Ischemic Stroke (ATLANTIS), European Cooperative Acute Stroke Study (ECASS) and the National Institutes of Neurological Disorders and Stroke (NINDS). Industry giants Genentech and Boehringer Ingelheim Pharmaceuticals funded some of the work.

The clinical trials compared the effects of the random use of recombinant tissue plasminogen activator (rt-PA) or a placebo for stroke patients. rt-PA is an artificially made compound that changes the structure of plasminogen � a precursor to the anticoagulant protein plasmin. This alteration then instigates the clot's breakdown.

Treatment was started within six hours of the stroke. Neurological scales that measured post-stroke disability were employed to assess improvement. As well, researchers looked at the incidence of uncontrolled bleeding, which can occur with the clot-busting chemical.

Patients treated within 90 minutes of a stroke showed the most benefit. Even after a delay of four hours, some improvement was produced. But after that the benefits diminished as time marched on. By about six hours, the clock ran out and any thrombolytics administered at this point had virtually no effect.

The authors of The Lancet paper have determined that a target time of an hour and a half would be the best window to shoot for in thrombolytic treatment of stroke.

"Although rapid stroke treatment presents a great challenge to physicians and may require substantial changes in many healthcare systems, we now have stronger evidence that rapid early treatment offers the best chance of recovery for acute ischemic stroke patients," said Dr John Marler, one of the study authors.

The analysis also uncovered that patients who got to the hospital faster (after suffering a stroke) were those in need of more attention than those with milder discomfort. The greatest effect of early thrombolytic treatment is in those who have the most to gain.

"This study confirms that door-to-needle time is just as critical in stroke as it is in heart attack," said NINDS director Story Landis.