Stroke is the second leading cause of death worldwide and a major cause of disability. It occurs when the supply of blood to the brain is interrupted or reduced due to blood vessel blockage (ischaemic stroke) or rupture (haemorrhagic stroke).
Stroke can be fatal and those who survive can experience a wide range of disabilities depending on which part of the brain has been affected and how quickly they are treated. Fast diagnosis and treatment not only saves lives, it can drastically improve recovery.
“We’ve come a long way since the 1980s when there were no treatments for people who had just had a stroke and care was solely focussed on rehabilitation,” says Peter Sandercock, Emeritus Professor of Medical Neurology at the University.
Today, thanks to increased awareness of the early warning signs of stroke, victims are more likely to seek help straight away and to be admitted to specialist stroke units where they can be quickly scanned and receive drugs that reduce their chance of dying or becoming disabled.
Peter’s early work focused on identifying widely usable treatments for recent stroke victims.
“We tested blood thinning drugs, following the model of trials that were designed to reliably and easily assess the effects of simple treatments on survival following a heart attack,” Peter explains.
He was involved in setting up the first large-scale International Stroke Trial (IST) to investigate the effects of the drugs, aspirin and heparin, on acute stroke, comprising nearly 20,000 patients entering 467 hospitals across 36 countries. The first IST trial showed that administering aspirin within 48 hrs of a stroke improved patients’ short and long-term outcomes. Aspirin is now a well-established basic treatment for ischaemic stroke and transient ischaemic attack (or TIA, often called a ‘mini-stroke’).
The latest trial Peter was involved with, the third IST trial (IST-3), was the largest ever clinical trial of the clot busting drug alteplase for acute stroke. In the mid 1990’s, alteplase was the only approved drug for acute ischaemic stroke, but it was not widely used at the time, especially in older patients, due to uncertainty about whether the risk of the drug causing a fatal bleed in the brain outweighed the benefit of increasing the likelihood of survival without disability.
Expanding treatment opportunities
The IST-3 trial showed that the outcomes of patients over 80 years of age improved if they were given alteplase within the first three hours of stroke symptoms, and had a scan confirming that the stroke was due to a blocked artery and not due to bleeding.
As Peter explains, a very important part of the trial was training hospital teams to diagnose ischaemic stroke and administer the drug quickly. “Significant changes in the system of care had to be implemented to be able to carry out this research but, as a result, once the results of the trial were available, all 156 participating hospitals were primed to offer alteplase to their patients,” he says.
To further understand which patients are most likely to benefit from alteplase treatment, Peter worked closely with Professor Joanna Wardlaw, Chair of Applied Neuroimaging at the University, to collate data from all groups trialling the drug in acute stroke patients. So far, these analyses have reinforced the finding that early treatment is best. Ongoing work is examining whether alteplase is still beneficial for stroke patients with unclear onset times.
The IST-3 trial also showed that even patients with scans showing brain damage due to the stroke and/or signs of previous damage due to a prior stroke or age-related neurodegenerative disease, still benefitted from treatment with alteplase. “Our results indicated that alteplase should be more widely used,” Joanna says.
Cost-effective measures for selecting the right treatment
Imaging technologies, CT and MRI scanning, are the only way to determine what type of stroke a patient has had and therefore the treatment they will require. Joanna has been examining the most effective ways to use these technologies for assessing stroke patients and their eligibility for thrombolytic treatment.
Her team has shown that the most cost-effective way to manage patients with stroke is to use CT scanning straight away. Compared with MRI, CT scanning is faster, cheaper and easier to use in acute stroke. Although MRI scans can be very sensitive to the features of stroke, they may not always capture them.
“For every 100 people who are clinically diagnosed with a mild stroke, 30 may not show the signs of it on an MRI scan, but they should still be treated,” Joanna says. “It is important to recognise that clinical assessment forms the basis of stroke diagnosis; imaging should be considered a supporting tool.”
MRI scans can also be useful to detect signs of acute brain ischaemia in about a third of TIAs, or to determine the cause of stroke in patients who cannot be scanned until more than five days after stroke, when CT scans can no longer distinguish whether the patient has suffered an ischaemic or a haemorrhagic stroke. However, Joanna notes that there are many other highly justified uses of MRI such as cancer screening that are competing with its use in stroke.
As a direct result of Joanna and Peter’s work, international clinical stroke guidelines recommend immediate CT scanning after acute stroke and administering alteplase for acute ischaemic stroke to a wider group of patients, including those over the age of 80. These recommendations have resulted in more patients receiving thrombolytic treatment and better long-term health outcomes after acute stroke.
“In the last 20 years, the treatment of acute stroke has changed beyond recognition,” says Joanna. “We’ve gone from thinking that nothing could be done, to being able to offer thrombolytic treatment or thrombectomy [a surgical procedure to remove clots] that improve survival and patients’ quality of life”.
Moreover, there is growing evidence that even if the treatment isn’t administered straight away, but many hours after the symptoms have started, it is still beneficial.
However, as Peter warns, the global burden of stroke is not declining. The age of stroke patients in high-income countries is rising, which means they are likely to have comorbidities that predispose them to complications after stroke. In addition, the prevalence of stroke in low-and-middle-income countries is rising, possibly reflecting increased exposure to risk factors and poor control of hypertension. Expanding the therapeutic window for stroke treatment is a great start, but without urgent implementation of effective prevention strategies in low-income countries, the global stroke burden will probably continue to grow.