Many people who suffer major strokes while asleep can benefit from having damaging blood clots removed from their brains long after the time when such a treatment was previously known to be effective, a new federally funded study shows. But it all depends on getting good pictures of the brain as soon as possible.
In a report in the New England Journal of Medicine, researchers with the Defuse 3 trial reported Wednesday that patients whose MRI scans show a good amount of living brain tissue can benefit from having blood clots fished out of large vessels in their brains between six and 16 hours after they were last known to be well.
“They used imaging that quickly measures the amount of irreversible stroke that a patient has in comparison to the amount of stroke that the patient may still develop,” said Dr. Chris Streib, a stroke neurologist at the University of Minnesota who served as one of the primary investigators on the study. “They’ve shown that at least through 16 hours, there is a very clear benefit from treating patients, even outside of the six-hour window.”
Doctors say the findings may be particularly important for patients who live far away from major stroke centers and those who wake up with stroke symptoms but don’t know when it happened.
Ischemic strokes, which make up about 85 percent of strokes, happen when a blood vessel in the brain becomes blocked, causing brain cells to die off rapidly.
Other recent studies have shown benefits for removing large-vessel blockages up to six hours after a stroke, but the Defuse 3 trial found that patients can benefit for up to 16 hours if imaging shows that blood flow can be adequately restored to large sections of the brain, and the brain isn’t already too far gone.
The clot-removal procedure, called endovascular mechanical thrombectomy, requires an approved medical device sold by companies like Medtronic, Stryker or Penumbra, all of which were included in the trial. The Defuse 3 study, funded by the National Institutes of Health, was announced Wednesday during the American Heart Association’s annual stroke conference, in Los Angeles.
The American Heart Association also published updated guidelines on Wednesday that say it’s now considered safe to treat large vessel strokes with thrombectomy in “selected patients” up to 16 hours after stroke.
“We welcome and endorse these new guidelines as a positive step toward treating stroke patients who previously would have faced limited — or no — treatment options,” Medtronic Neurovascular General Manager Stacey Pugh said in a statement.
The Defuse 3 study found that the 90-day death rate was lower for patients who had a thrombectomy vs. those who did not — 14 percent vs. 26 percent. More pronounced was the rate of “functional independence” among the thrombectomy patients — 45 percent vs. 17 percent after three months. Doctors say functional independence is important to consider because major strokes can leave people alive but requiring lifelong help with daily activities.
“This is a big proportion of patients who would either be disabled or dead in three months after these types of strokes,” said Dr. Ganesh Asaithambi, a stroke neurologist at United Hospital in St. Paul who did not take part in the study. The results show that a mechanical thrombectomy can work for “patients who otherwise would not be eligible for a mechanical thrombectomy purely from a time-window perspective.”
Streib called the findings “exciting” and said they reinforce the need for all stroke patients to have a CT angiogram performed quickly to tell whether they have a large-vessel blockage, even if the patient is elderly or lives hours from a comprehensive stroke center.
“With the six- to 16-hour window [and 24-hour time window from a similar trial, DAWN], you really have very few patients who are falling outside of these extended time windows. And even if they do, it is worth considering that the imaging selection parameters for delayed mechanical thrombectomy may still apply,” Streib said via e-mail. “So if somebody has an unknown time of onset but their imaging appears extremely favorable, I would consider treating that patient with mechanical thrombectomy.”
The study examined 183 patients at 38 U.S. hospitals, and was ended early because the results were so conclusive that it would have been unethical to continue randomizing patients to the non-thrombectomy group, especially in light of other research.
Another study called the DAWN Trial, which was published last November in NEJM, found that 49 percent of patients treated with Stryker’s Trevo clot removers were functionally independent after three months, compared to 13 percent in the control group, after having the same type of neuroimaging analysis as in Defuse 3. DAWN was a company-sponsored study that tested one brand of device between six and 24 hours from stroke onset.
Patients in both studies were selected only if their brain scans showed blockages in the middle-cerebral artery or the internal-carotid artery, where major blockages can be especially damaging to brain tissue.
In Defuse 3, patients were admitted if they had less than 70 milliliters (ml) of dead brain tissue and at least 15 ml of tissue that could be preserved if blood flow was restored.
Two of the 92 thrombectomy patients in Defuse 3 had device-related complications — one had a vessel perforation resulting in a hemorrhage associated with a greater degree of disability, and the other person had an artery narrowing called vasospasm that didn’t lead to neurological worsening, the study said. Overall, serious adverse effects occurred in 43 percent of thrombectomy patients and 53 percent treated with traditional methods alone.
Doctors should make sure that all stroke patients have the necessary imaging and analysis done to see if they might benefit from a thrombectomy, including patients in their 80s or 90s.
“It’s every single patient. It doesn’t matter if you are 89 years old,” Streib said. If the patient meets the selection criteria after imaging, “there’s really no suggestion from this trial or prior trials that there are groups of patients that do not benefit.”