Treatment with acetylsalicylic acid (ASA) or heparin is associated with an increased risk for symptomatic intracranial hemorrhage (sICH) in patients with ischemic stroke who are undergoing endovascular therapy (EVT), new data show.
In this population, ASA and heparin are each associated with an approximately doubled risk for sICH when administered during EVT.
“We did not find any evidence for a beneficial effect on functional outcome,” investigator Wouter van der Steen, MD, research physician and PhD student at Erasmus University Medical Center, Rotterdam, the Netherlands, told this news organization. The possibility that a positive effect would be observed if the trial were continued was considered negligible, he added.
The researchers stopped the trial for safety reasons and recommend avoiding the evaluated dosages of both medications during EVT for ischemic stroke, said Dr. van der Steen.
He presented the findings from the MR CLEAN-MED trial at the European Stroke Organisation Conference (ESOC) 2021, which was held online.
Trial stopped for safety
Previous research has supported the safety and efficacy of EVT for ischemic stroke. Still, more than 30% of patients do not recover, despite fast and complete recanalization. Incomplete microvascular reperfusion (IMR) could explain this incomplete recovery, the researchers note.
Microthrombi, which occlude distal vessels, and neutrophil extracellular traps can cause IMR. This problem can be reduced through treatment with ASA, which has an antithrombotic effect, or with heparin, which dissolves neutrophil extracellular traps, they add. Although these drugs are associated with good clinical outcomes, they entail an increased risk for sICH.
The investigators conducted the multicenter, randomized controlled MR CLEAN-MED trial to evaluate the effect of intravenous (IV) ASA and heparin, alone or in combination, during EVT for acute ischemic stroke. Treatment was open label, but outcome assessment was blinded. Eligible participants were adults with a National Institutes of Health Stroke Scale (NIHSS) score of greater than or equal to 2 and an anterior circulation large-vessel occlusion for whom EVT could be initiated in fewer than 6 hours.
Investigators randomly assigned patients to receive or not to receive ASA. Within each of these two treatment groups, patients were randomly assigned to receive no heparin, low-dose heparin, or moderate-dose heparin.
ASA was given in a loading dose of 300 mg. Patients who were given low-dose heparin received a loading dose of 5,000 IU followed by 500 IU/h for 6 hours. Patients who received moderate-dose heparin were given a loading dose of 5,000 IU followed by 1,250 IU/h for 6 hours.
The study’s primary outcome was Modified Rankin Scale (mRS) score at 90 days. Secondary outcomes were NIHSS score at 24 hours, NIHSS score at 5 to 7 days, and recanalization grade at 24 hours on CT angiography or MRI. The primary safety outcomes were sICH and death within 90 days.
An independent, unblinded data and safety monitoring board (DSMB) assessed the risk for the primary safety outcomes throughout the trial. The board performed interim analyses of safety and efficacy for every 300 patients.
After the fourth safety assessment, the DSMB recommended that enrollment in the moderate-dose heparin arm be discontinued for safety reasons. Enrollment in other arms continued.
After the second interim analysis, the DSMB advised that the trial steering committee be unblinded to decide whether to stop or continue the trial. The steering committee decided to stop the trial for reasons of safety.