The safety of a controversial clot-busting drug has been investigated by researchers, who have shown a modified dosage can reduce serious bleeding in the brain and improve survival rates.
It is hoped the findings from the trial of more than 3,000 patients in 100 hospitals worldwide could change the way the most common form of stroke is treated globally.
Intravenous rtPA (or alteplase) is given to people suffering acute ischaemic stroke and works by breaking up clots blocking the flow of blood to the brain.
However, it can cause serious bleeding in the brain in around five per cent of cases, with many of these proving fatal.
The study was conducted by teams at the George Institute for Global Health, and the University of Leicester's Department of Cardiovascular Sciences. The UK arm of the trial was funded by the Stroke Association.
National Coordinator of the study in the UK, Professor Tom Robinson of the University said: "This trial was a randomised controlled trial, which is the gold standard for determining whether a medicine actually has the desired effect.
"The results provide important information when discussing clot-busting treatment with patients and their families.
"Most patients who have a major stroke want to know they will survive but without being seriously dependent on their family. We have shown this to be the case with the lower dose of the drug.
"Stroke is the fourth leading cause of death in the UK and the leading cause of adult neurological disability. There are over 150,000 strokes each year in the UK, one in four of whom are in people of working age.
"Currently, approximately 11 per cent of stroke patients receive thrombolysis treatment for stroke in the UK."
Professor Craig Anderson, Lead Author of the study published in The New England Journal of Medicine, said: "At the moment you could have a stroke but end up dying from a bleed in the brain. It's largely unpredictable as to who will respond and who is at risk with rtPA.
"What we have shown is that if we reduce the dose level, we maintain most of the clot busting benefits of the higher dose but with significantly less major bleeds and improved survival rates. On a global scale, this approach could save the lives of many tens of thousands of people.
"There is a trade off with the lower dose in regards to recovery of functioning, but being alive is surely preferable to most patients than suffering an early death."
Dr Dale Webb, Director of Research and Information at the Stroke Association, said: "We've known for a while that giving stroke patients alteplase carries the risk of bleeding in the brain which can be fatal.
"However, an independent review in the UK concluded last year that the benefits outweigh the risks. This new study will be welcome news for clinicians and patients, because it suggests that we can reduce the risk of bleeding with a lower dose of alteplase, whilst retaining most of its benefit."
These differing effects meant that the trial was unable to show conclusively that the low dose was as effective as standard dose rtPA in terms of survivors being free of any disability.
rtPA is used to dissolve clots that block a blood vessel in a patient's brain within the first few hours after the onset of stroke symptoms.
Yet, because many people with stroke arrive at hospital after this crucial time window, only around five per cent of eligible people currently receive this therapy in most countries.
Concerns over the risks of bleeding on the brain associated with rtPA have prompted independent reviews of the research evidence in Australia and the UK.
Professor Tom Robinson is also from the NIHR Leicester Cardiovascular Biomedical Research Unit.
- Compared to standard dose (0.9mg/kg body weight), the lower dose (0.6mg/kg) of rtPA reduced rates of serious bleeding in the brain, known as intracerebral haemorrhage (ICH), by two thirds.
- After 90 days, 8.5 per cent of patients had died after receiving low dose rtPA, compared to 10.3 per cent who received the standard dose.
- The survival benefit was offset by a slight rise in the amount of people suffering residual disability. For every 1000 patients treated, low dose rtPA, compared to the standard dose, 41 more people had physical disabilities, such as needing help dressing or walking, but 19 fewer people died.
Notes to editors:
An audio interview with Professor Tom Robinson is available here (to be set live once embargo lifts): https://soundcloud.com/university-of-leicester/could-a-controversial-stroke-drug-save-lives
The audio interview can be sent to journalists in advance of the embargo lifting via WeTransfer. Email Peter Thorley email@example.com to request a copy of the audio.
- For further details, to arrange an interview or more photographs, email firstname.lastname@example.org or Fiona.email@example.com or call or 01604 882342.
- Please note Professor Robinson is away at an academic conference but will pick up emails on firstname.lastname@example.org
The George Institute for Global Health
The George Institute for Global Health is improving the lives of millions of people worldwide through innovative health research. Working across a broad health landscape, the Institute conducts clinical, population and health system research aimed at changing health practice and policy worldwide. The Institute has a global network of medical and health experts working together to address the leading causes of death and disability worldwide. Established in Australia and affiliated with The University of Sydney, the Institute today also has offices in China, India and the United Kingdom, and is also affiliated with Peking University Health Science Centre, the University of Hyderabad and the University of Oxford. The Institute has been ranked among the top 10 global institutes for impact for the last several years.
The Stroke Association
A stroke is a brain attack which happens when the blood supply to the brain is cut off, caused by a clot or bleeding in the brain. There are around 152,000 strokes in the UK every year and it is the leading cause of complex disability. There are around 1.2 million people in the UK living with the effects of stroke.
The Stroke Association is a charity. We believe in life after stroke and together we can conquer stroke. We work directly with stroke survivors and their families and carers, with health and social care professionals and with scientists and researchers. We campaign to improve stroke care and support people to make the best recovery they can. We fund research to develop new treatments and ways of preventing stroke. The Stroke Helpline (0303 303 3100) provides information and support on stroke. More information can found at http://www.stroke.org.uk
The NIHR Leicester Cardiovascular Biomedical Research Unit
The NIHR Leicester Cardiovascular Biomedical Research Unit is funded by the NIHR. The Leicester Cardiovascular Biomedical Research Unit at Glenfield Hospital aims to improve the diagnosis, prognosis and treatment of cardiovascular diseases. The unit provides state-of-the-art facilities, equipment and staff to assist researchers in their complex projects. It is one of 20 units around England funded by the NIHR. It is a partnership between the University of Leicester and University Hospitals of Leicester NHS Trust. The Unit's director is Professor Sir Nilesh Samani and the manager is Dr Martin Batty. http://www.le.ac.uk/bru
The National Institute for Health Research (NIHR)
The NIHR is funded by the Department of Health to improve the health and wealth of the nation through research. The NIHR is the research arm of the NHS. Since its establishment in April 2006, the NIHR has transformed research in the NHS. It has increased the volume of applied health research for the benefit of patients and the public, driven faster translation of basic science discoveries into tangible benefits for patients and the economy, and developed and supported the people who conduct and contribute to applied health research. The NIHR plays a key role in the Government's strategy for economic growth, attracting investment by the life-sciences industries through its world-class infrastructure for health research. Together, the NIHR people, programmes, centres of excellence and systems represent the most integrated health research system in the world. For further information, visit http://www.nihr.ac.uk. Twitter: @LeicesterBRU
New England Journal of Medicine