Clot-retrieval devices failed to improve stroke-related disability
A stroke survivor’s chances of living independently after 90 days are not improved by the use of devices inserted into the artery to dissolve or remove a stroke-causing clot shortly after the onset of symptoms, according to a randomized controlled trial involving 656 patients.
The study, funded by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health, compared the intra-arterial device-based approach plus the current standard of intravenous (IV) tissue plasminogen activator (t-PA), a clot-busting drug with IV t-PA therapy alone. The research will be presented at the International Stroke Conference 2013 in Honolulu, Hawaii and simultaneously published online Feb. 7 in the New England Journal of Medicine.
“This is the largest trial of an intra-arterial intervention for acute ischemic stroke, and is important because it shows that the addition of devices to treat clots within the brain artery was no more effective than treatment with IV t-PA alone,” said Walter J. Koroshetz, M.D., deputy director, NINDS. “Such devices are already widely used in clinical practice based on dramatic improvements seen in individuals, but without evidence supporting their overall clinical effectiveness in a large group.”
Intra-arterial treatment is known to be associated with significant risk; 16 percent of the patients in the study had complications from the minimally invasive surgical procedure. The Interventional Management of Stroke, or IMS-III, is the only trial designed to assess the overall balance between risk and benefit of intra-arterial treatment in acute stroke patients.
Eliminating a clot from within a vessel involves threading a catheter through an artery in the groin up to the site of a clot in the brain, and then administering t-PA directly on the clot, which dissolves it, or removing it via coiled wires or a stent system. Based on earlier studies, researchers anticipated that adding an intra-arterial approach to standard IV t-PA would reduce stroke-related disability by providing a means to eliminate very large clots that would otherwise persist despite IV t-PA, according to the researchers led by Joseph Broderick, M.D., of the University of Cincinnati Academic Health Center.
Participants, ages 18-82 years, were enrolled in the study starting in 2006. By April 2012, after 656 of the 900 planned participants had been treated, the study’s Data and Safety Monitoring Board advised that the investigation should be stopped early because 90-day outcomes showed that the benefit was not substantially different between the groups. Patients in the IV t-PA alone group (39 percent) were just as likely as those in the combination therapy group (41 percent) to be functionally independent.
What is a stroke?
A stroke happens when the blood supply to the brain is disturbed in some way. As a result, brain cells are starved of oxygen. This causes some cells to die and leaves other cells damaged.
Types of stroke
Most strokes happen when a blood clot blocks one of the arteries (blood vessels) that carries blood to the brain. This type of stroke is called an ischaemic stroke.
Transient ischaemic attack (TIA) or ‘mini-stroke’ is a short-term stroke that lasts for less than 24 hours. The oxygen supply to the brain is quickly restored and symptoms disappear. A transient stroke needs prompt medical attention because it indicates a serious risk of a major stroke.
Cerebral thrombosis is when a blood clot (thrombus) forms in an artery that supplies blood to the brain. Blood vessels that are furred up with fatty deposits (atheroma) make a blockage more likely. The clot prevents blood flowing to the brain and cells are starved of oxygen.
Cerebral embolism is a blood clot that forms elsewhere in the body before travelling through the blood vessels and lodging in the brain. In the brain, it starve cells of oxygen. An irregular heartbeat or recent heart attack may make you prone to forming blood clots.
Cerebral haemorrhage is when a blood vessel bursts inside the brain and bleeds (haemorrhages). With a haemorrhage, blood seeps into the brain tissue and causes extra damage.
All patients in the study received IV t-PA therapy within three hours of their stroke symptoms. Within 40 minutes of that therapy, 434 patients who were randomized to the device-treatment group underwent angiography to identify arterial blockages. Those patients found to have a treatable blockage received intra-arterial therapy with one of five types of devices. The remaining 222 patients were randomized to receive IV t-PA alone.
Intra-arterial therapy was 40 percent more effective at removing clots and re-establishing blood flow but it did not improve disability due to stroke. “Our study highlights that improved reopening of arteries and delivery of blood flow to the brain is not a guarantee of improved clinical efficacy,” concluded Dr. Broderick, who led the team of researchers at 58 U.S. and international clinical centers.
The time to intra-arterial treatment was 32 minutes longer in IMS III compared with the two pilot studies that preceded it. This may be an important reason for the lack of clinical benefit despite substantially better revascularization with intra-arterial therapy as compared to IV t-PA. “We probably did not open the arteries quickly enough,” said Dr. Broderick.
Cutting the time to intra-arterial therapy poses significant challenges, given the logistics of assembling the treatment team and room and conducting the procedure, Dr. Broderick noted. In addition, most patients do not have immediate access to the level of care required to perform intra-arterial procedures. Instead, they are often treated with IV t-PA at a local hospital then transferred to another hospital, all of which further delays the time to treatment.
What risk factors for stroke can’t be changed?
Age - The chance of having a stroke approximately doubles for each decade of life after age 55. While stroke is common among the elderly, a lot of people under 65 also have strokes.
Heredity (family history) - Your stroke risk is greater if a parent, grandparent, sister or brother has had a stroke. Some strokes may be symptoms of genetic disorders like CADASIL (Cerebral Autosomal Dominant Arteriopathy with Sub-cortical Infarcts and Leukoencephalopathy), which is caused by a gene mutation that leads to damage of blood vessel walls in the brain, blocking blood flow. Most individuals with CADASIL have a family history of the disorder - each child of a CADASIL parent has a 50% chance of inheriting the disease. Visit the NINDS website or read the AHA/ASA scientific statement on this topic for more details about CADASIL.
Race - African-Americans have a much higher risk of death from a stroke than Caucasians do. This is partly because blacks have higher risks of high blood pressure, diabetes and obesity.
Sex (gender) - Stroke is more common in men than in women. In most age groups, more men than women will have a stroke in a given year. However, more than half of total stroke deaths occur in women. At all ages, more women than men die of stroke. Use of birth control pills and pregnancy pose special stroke risks for women.
Prior stroke, TIA or heart attack - The risk of stroke for someone who has already had one is many times that of a person who has not. Transient ischemic attacks (TIAs) are “warning strokes” that produce stroke-like symptoms but no lasting damage. TIAs are strong predictors of stroke. A person who’s had one or more TIAs is almost 10 times more likely to have a stroke than someone of the same age and sex who hasn’t. Recognizing and treating TIAs can reduce your risk of a major stroke. TIA should be considered a medical emergency and followed up immediately with a healthcare professional. If you’ve had a heart attack, you’re at higher risk of having a stroke, too.
IMS III sheds light on research gaps that need to be addressed in trials to develop evidence-based recommendations on the use of intra-arterial devices, said Scott Janis, Ph.D., program director, NINDS.
“These devices still may play a critical role in improving outcomes among people with serious strokes involving clots that cannot be cleared or are cleared very slowly by standard IV t-PA” Dr. Janis said.