Results of an international trial show that stroke survivors make a better recovery if they are given the clot-busting drug rt-PA in the first six hours following a stroke.

Led by the University of Edinburgh in Scotland, the international trial, known as IST-3, found that for every 1,000 patients that received the clot-buster within the first three hours of a stroke, 80 more survive and live without help from others, compared to patients not receiving the drug.

The IST-3 collaborative group write about their findings in a paper that was published online in The Lancet on 23 May. Alongside the trial results they also present an analysis of all other drug trials of rt-PA conducted in the last 20 years.

IST-3 stands for the third International Stroke Trial. Its aim was to find out whether a wider range than hitherto of patients treated within the first 6 hours from stroke onset might benefit.

One of the IST-3 group members, Professor Peter Sandercock, is Chief Investigator at Edinburgh’s Centre for Clinical Brain Sciences and Director of Edinburgh Neuroscience. He told the press:

“Our trial shows that it is crucial that treatment is given as fast as possible to all suitable patients.”

Rt-PA (recombinant tissue plasminogen activator) is a clot-busting drug that is given intravenously to patients who have suffered an acute ischemic stroke, where a blood clot interrupts the blood supply to the brain.

The multi-centre, randomized study involved more than 3,000 patients enrolled in over 150 hospitals in 12 countries, and is the world’s largest ever trial of rt-PA. Just over half the participants were over 80 years of age.

The damage from an ischemic stroke can be permanent or fatal. Symptoms of damage include paralysis down one side of the body and problems with speech.

But the benefits of rt-PA come at a price, said the researchers: there is a higher risk of death in the first seven days of treatment because the drug can cause a secondary bleed in the brain.

However, they conclude they saw the benefits in a wide range of patients, despite the risks. And, they pointed out, the higher risk of death from the drug needs to viewed in the context of deaths from stroke: without treatment, one third of stroke victims die, and another third are left permanently disabled and dependent on others.

Professor Joanna Wardlaw of the University of Edinburgh’s Centre for Clinical Brain Sciences, led the IST-3 Imaging team. She said:

“We have looked at data from more than 7,000 stroke patients worldwide. What we see is that the drug increases patients’ longer term recovery. But we need to find out why some people bleed and how to reduce this to increase the effectiveness of clot busting treatment.”

Support for the UK-based work came from the Medical Research Council, the Stroke Association UK, the Health Foundation UK, NIHR Stroke Research Network and NHS Lothian Health Board. Other groups in other countries, including Sweden, Norway, Australia, Poland, Italy and Switzerand also received funds from various state, academic and charitable bodies.

Written by Catharine Paddock PhD