Two different treatment approaches for stroke patients with large vessel occlusion—direct endovascular thrombectomy (EVT) compared with standard care comprising tissue plasminogen activator (tPA) before EVT—showed no differences in outcomes, according to two different studies presented at the International Stroke Conference 2021.
MR CLEAN-NO IV, which was performed in Europe, and SHRINE, conducted mainly in Asia, failed to support direct endovascular therapy as a better treatment. Both trials were also unable to prove the surgery was non-inferior to standard care, reported Yvo Roos, MD, PhD, professor of neurology at the Amsterdam University Medical Center.
“We did not show superiority or non-inferiority of direct endovascular treatment over intravenous alteplase followed by endovascular treatment. We found similar hemorrhage rates with or without intravenous alteplase administration before endovascular treatment," said Dr. Roos.
In 2015, the benefit of endovascular intervention in acute stroke involving occlusions of large arteries was proven as an addition to alteplase administration within a therapeutic window, noted Dr. Roos. The question since has been if alteplase is needed at all in these cases. Studies have hinted that not using alteplase resulted in the same outcome as using the tissue plasminogen activator, he added.
But, Dr. Roos said, the MR CLEAN-NO IV trial failed to prove that.
Just over 49 percent of the 273 patients assigned to direct endovascular intervention achieved a zero to two score on the modified Rankin Scale at discharge, compared with 51.1 percent among the 266 patients who first received alteplase before undergoing the EVT. The 5 percent greater risk for direct endovascular therapy in the latter group was not statistically significant.
The results did not prove superiority (95% CI 0.65-1.38). The pre-specified margin of non-inferiority was 0.80, indicating that non-inferiority could not be proven either, noted Dr. Roos.
The SHRINE trial had similar results, reported Raul Nogueira, MD, professor of neurology, neurosurgery, and radiology at Emory University in Atlanta.
Dr. Nogueira noted that the trial only applied to centers that could provide thrombectomy-capable services with a fast workflow—not community hospital stroke centers. The SHRINE trial pooled the results of two major trials (SKIP and DEVT) that were conducted in Asia. While the trials hinted that there was a benefit to direct EVT without alteplase on board, the researchers were concerned that the limitations and size of the trial didn't provide a complete picture.
In this trial, the researchers pre-specified that to satisfy non-inferiority hypothesis, the lower boundary of the 95% confidence interval for the primary outcome—a 90-day modified Rankin Score of zero to two—needed to exceed 0.85 in the endovascular group compared to the bridging group, those who received alteplase before endovascular intervention.
In this case, the outcome favored endovascular therapy (adjusted odds ratio 1.23; 95% CI 084-1.92), falling outside the pre-specified margin (p=0.06).
“These studies clearly show that it doesn't matter whether you have tPA first when you perform endovascular procedures on stroke patients," said Louise McCullough, MD, PhD, the Roy M. and Phyllis Gough Huffington Distinguished Chair and professor of neurology at the University of Texas Health Science Center in Houston. “However, I would never withhold tPA unless there was a very clear reason not to such as if the patient had a high rate of bleeding."
“My preference is always to give a lytic until it is proven that it hurts somebody to do that," Dr. McCullough said. “There are definitely more groin hematomas but the risk of not giving them anything and letting them infarct in some sort of disaster is too big of a risk for me."
Dr. McCullough said one unanswered question is whether one should be using alteplase or tenecteplase. “I think eventually we will shift to tenecteplase because of its ease of use," she said.
Dr. Roos disclosed relationships with industry through the Collaboration for New Treatments of Acute Stroke, which includes non-governmental organizations, government organizations, as well as Medtronic and Top Sector Life Sciences. He is also a shareholder of Nico Lab. Dr. Nogueira disclosed relationships with Stryker Neurovascular, Medtronic, Cerenovus, Phenox, Anaconda, Genentech, Biogen, Prolong Pharmaceuticals, IschemaView, Brainomix, Corindus Vascular Robotics, Vesalio, Viz-AI, Ceretrieve, and Sensome. Dr. McCullough had no disclosures.
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ISC Abstract LB3: LeCouffe NE, Kappelhof M, Treurniet KM, et al, for the MR CLEAN-NO IV Investigators. Intravenous thrombolysis followed by endovascular thrombectomy versus direct endovascular thrombectomy: A randomized controlled trial.
ISC Abstract LB4: Nogueira RG, Kimura K, Matsumaru Y, et al. Systemic thrombolysis randomization in endovascular stroke therapy (SHRINE) collaboration.