Is there a drug for stroke?

Cochrane

Question

We wanted to compare the safety and effectiveness of drugs used to dissolve blood clots (thrombolysis) with placebo or no treatment in the early stages of ischemic stroke to see if these drugs improve post-stroke endpoints.

background

Most strokes are caused by a blockage of an artery in the brain with a blood clot. Immediate treatment with drugs that dissolve blood clots (thrombolytic) can restore blood flow before any major damage to the brain has occurred. That could mean that people have a better chance of a good recovery after a stroke. However, thrombolytic drugs can also cause serious bleeding in the brain, which can be fatal. Thrombolytic therapy has been investigated in many randomized studies in acute ischemic stroke. The thrombolytic drug alteplase was approved for treatment within three hours of stroke in the United States and Canada, and within 4.5 hours in most European countries. The number of people who are successfully using this treatment is increasing.

Study characteristics

We searched the literature for studies published before November 2013 and found 27 studies with a total of 10,187 participants. Most of the data come from studies examining a specific drug (rt-PA, recombinant tissue plasminogen activator) that is administered intravenously up to 6 hours after the onset of acute stroke. But some other drugs were also tested. The drugs were given at different times after the stroke and into an artery in the brain rather than a vein in the arm. All studies compared a thrombolytic drug with placebo (control group). Most of the studies included patients with moderate to severe stroke. All of the studies were conducted in hospitals that had experience treating people with stroke. Differences between the studies mean that not all studies provide information on all outcomes, but we used all available data. Most studies included participants after cerebral hemorrhage was ruled out as the cause of symptoms using a computed tomography (CT) scan of the brain (a few studies used magnetic resonance imaging instead).

Main results

There is general agreement between the earlier and one more recent study (IST-3) added to this update on all major endpoints and between the 12 studies examining rt-PA and the 15 studies examining other thrombolytic drugs. The main difference between IST-3 and the previous studies was that IST-3 had many participants who were over 80 years of age. Thrombolytic treatment can reduce the risk of long-term dependence on other people for everyday activities. Even so, there is an increased risk of bleeding in the brain, which also increases the risk of early death. Once the early risk of bleeding was over, 3 or 6 months after the stroke, people who received thrombolytic drugs were more likely to recover from their stroke and be more independent - especially if they were treated within the first 3 hours after the stroke . Older people benefited just as much as younger people. Concomitant use of aspirin and medication to dissolve blood clot increases the risk of bleeding and should be avoided. Further analysis of individual factors in patient data, such as pre-treatment brain imaging results, and different modes of treatment, may provide more information than the aggregated data we have used here. Meanwhile, people who think they are having a stroke should get to hospital as soon as possible, have a stroke specialist, have a brain imaging exam, and get thrombolytic treatment as soon as possible. Sufferers shouldn't hesitate because they think they may be 'too old' for treatment. Treatment is very effective when started within three hours of the stroke and clearly improves outcome when given up to 4.5 hours after the stroke. When administered later, however, the effects are less clear and are currently still being investigated in studies. More information from studies of people with minor strokes is needed to see if the benefits of thrombolytic drugs outweigh the risk of bleeding.

Quality of the evidence

The evidence comes largely from well-conducted randomized trials led by stroke experts. Some studies (8/27) were led by pharmaceutical companies that make the thrombolytic drugs. However, most of the studies (19/27, which included most of the participants) were funded by governments or nonprofits that are independent from pharmaceutical companies. These results are applicable to a wide range of patients with many different stroke severities and other medical conditions.