Giving blood-thinning medications to individuals who had an ischemic stroke (clot-related stroke) didn’t improve their outcomes 90 days later, in keeping with preliminary groundbreaking research presented today on the American Stroke Association’s 2024 International Stroke Conference. The meeting, held in person in Phoenix on February 7–9, 2024, is the world’s premier meeting for researchers and clinicians on the science of stroke and brain health.

These results come from the MOST (Multi-Arm Optimization of Stroke Thrombolytic) study. MOST is a 57-site U.S. study that was halted after an independent data and safety review board reviewed the outcomes of the primary 500 patients of a planned 1,200 participants and concluded that advantages were highly unlikely to be realized at the top of the study. The study searched for improvements in functional outcomes after 90 days.

Once we began the study, we believed the drugs would improve outcomes, so we were surprised by the negative results. Nevertheless, we designed the study in order that we could effectively answer the query about two blood thinners in a single study. We now have definitely done it and we’re pleased to have the option to reply this query.”

Opeolu M. Adeoye, MD, lead creator of the study and BJC HealthCare Distinguished Professor of Emergency Medicine and chair of emergency medicine at Washington University School of Medicine in St. Louis, Missouri

“A lot of our approaches to treating stroke come from treating heart attacks. In previous studies, we first tested to make sure that these drugs were protected for treating stroke, after which brought MOST to market to verify their safety and see in the event that they would work. improve functional outcomes and reduce disability after stroke,” Adeoye said.

The MOST study enrolled adults with ischemic stroke severe enough to likely require rehabilitation. All participants received a regular clot-busting drug to dissolve the clot (thrombolysis) inside three hours of the stroke onset. Participants were then randomly assigned to one among three groups for added treatment: one group received the blood-thinning drug argatroban inside 75 minutes of receiving the clot-busting drug, followed by an infusion of argatroban over 12 hours. The second group received an initial dose of the blood thinner eptifibatide inside 75 minutes of the clot-busting drug, followed by a 2-hour infusion of eptifibatide and a 10-hour infusion of a saline placebo. The control group received a clot-thinning drug and a placebo (12-hour intravenous infusion of saline containing no blood-thinning drug).

The first endpoint was the study participant’s level of physical function 90 days after ischemic stroke. Physical fitness level was assessed using the Modified Rankin Scale, or mRS, a 6-point disability scale. The videotaped assessment was scored by an independent neurologist reviewer who was unaware of what treatment the patients received. The mRS rating was translated right into a utility-weighted mRS using validated patient and physician rankings of functional outcomes, leading to a 0- to 10-point scale, with higher scores indicating greater treatment profit. Interim evaluation was scheduled at baseline and scheduled after 500 patients had been enrolled. As well as, the Data Safety and Monitoring Board (DSMB) reviewed safety data after every 30 enrolled patients, specifically searching for cases of cerebral bleeding.

The evaluation showed that among the many 514 patients enrolled before the DSMB paused the study in July 2023:

• Each blood thinners used didn’t significantly increase the chance of brain bleeding.
• Nevertheless, neither of the 2 blood thinners improved outcomes in stroke survivors. On a utility-weighted mRS scale of 0 to 10, patients receiving placebo averaged 6.8, patients receiving argatroban averaged 5.2, and patients receiving eptifibatide averaged 6.3. (Disability types will vary, nonetheless, individuals with a 6-point utility-weighted mRS scale are expected to have difficulty performing activities of day by day living without assistance and support.)

Details and background of the study:

• The three-arm study was conducted at 57 hospitals in america between October 2019 and July 2023.
• All participants had an ischemic stroke (attributable to a clot) that scored 6 or higher on the National Institutes of Health Stroke Severity Scale and was considered a moderately severe stroke.
• The study enrolled 514 adults before it was stopped; participants had a median age of 68 years; roughly 50% were women; and roughly 25% identified as Black adults.
• Participants were treated inside three hours of the onset of stroke symptoms (or the time they were last seen well) using a regular approach to thrombolysis (the administration of clot-busting drugs to dissolve the clot).
• Moreover, 44% of patients in all three groups underwent interventional clot removal, called thrombectomy.
• At enrollment, participants were randomized to receive a blood thinner or placebo inside 75 minutes of thrombolysis: 59 received argatroban; 228 received eptifibatide; and 227 received a placebo.
• The first preventive measure was the occurrence of bleeding within the brain (symptomatic intracranial hemorrhage) inside 36 hours of receiving one among the 2 blood thinners. Safety measures were reviewed by the DSMB for the study after enrollment of each 30 patients.

The attending physicians were aware whether each patient was given a blood thinner or a placebo. Nevertheless, neither the patients nor the specialists assessing the outcomes were aware which patients in either group received the blood thinner or the placebo.

“Moreover, we were unable to guage the possible advantage of administering these or similar blood thinners directly into an artery within the stroke area, reasonably than administering the drugs systemically through a vein, as was done on this study,” Adeoye said.

For patients undergoing thrombectomy (the mechanical removal of a clot that causes a stroke), research is ongoing to find out whether administering blood-thinning medications to the affected artery can improve outcomes.

The study was conducted at National Institutes of Health StrokeNet sites. StrokeNet was established to conduct small and huge clinical trials and research to advance acute stroke treatment, stroke prevention, and lifelong stroke recovery and rehabilitation. Other principal investigators were Andrew D. Barreto, MD, MS; Joseph P. Broderick, M.D.; Colin P. Derdeyn, M.D.; Dr. Jordan Elm; and James C. Grotta, M.D. For a whole list of authors and their disclosures, see the abstract.

All study authors reported funding from the National Institute of Neurological Disorders and Stroke, a division of the National Institutes of Health.