MOST: Blood Thinners Lack Improvement in Ischemic Stroke Outcomes

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Blood thinners added to clot-busting medication did not improve 90-day stroke outcomes, leading to early discontinuation of the MOST trial.

The addition of blood thinners to clot-busting medications did not improve 90-day outcomes among people with ischemic stroke, according to new late-breaking science at the American Stroke Association’s International Stroke Conference 2024.1

With plans to include ≥1,200 patients with ischemic stroke, Multi-Arm Optimization of Stroke Thrombolysis (MOST) trial enrollment was stopped after an independent data and safety monitoring board observed no indication of benefit among the first 500 enrolled patients. The board determined it unlikely a benefit would be observed if the research was completed.

“When we began the trial, we believed the medications would improve outcomes, so we were surprised with the negative results,” said lead study author Opeolu M. Adeoye, MD, MS, BJC Healthcare Distinguished Professor of Emergency Medicine, and chair of the department of emergency medicine at Washington University School of Medicine.2 “However, we designed the trial to allow us to efficiently answer the question for two blood-thinning medication medications in one trial. We have definitely done that and are pleased with the ability to answer this question.”

The three-arm MOST study was conducted at 57 hospitals in the United States between October 2019 and July 2023.1 All included participants with ischemic stroke rated a ≥6 on the National Institutes of Health Stroke Severity Scale, considered a moderately severe stroke, and likely required rehabilitation. Participants in MOST received a standard clot-busting medication to dissolve the thrombolysis within 3 hours of stroke onset.

A total of 514 adults were enrolled in the trial before the stoppage, with an average age of 68 years, 50% women, and 25% self-identifying as Black. At the time of enrollment, individuals were randomized to receive a blood thinner or placebo within 75 minutes of thrombolysis, including argatroban (n = 59), eptifibatide (n = 228), or saline placebo (n = 227). Across all 3 cohorts, 44% of patients underwent thrombectomy.

Those providing care were aware of whether a blood thinner or placebo was given to each patient, but the patient remained blinded to the treatment assignment. Each videotaped assessment was evaluated by an independent neurologist reviewer who was also blinded to the treatment group.

For the analysis, the primary outcome was the participant's level of physical function at 90 days after ischemic stroke. Function levels were determined using the 6-point modified Rankin score (mRS) disability scale. Investigators then translated the mRS score into a utility-weighted mRS using a validated rating of functional outcomes by patients and physicians.

A 0 to 10- utility-weighted scale was created, with a higher score representing a higher functional benefit from treatment. The interim analysis occurred after the first 500 patients were enrolled in MOST. A data safety and monitoring board (DSMB) reviewed safety data after every 30 patients to investigate occurrences of symptomatic intracranial hemorrhage after blood thinner use.

Before the trial was halted in July 2023, data analysis revealed argatroban and eptifibatide did not significantly increase the risk of bleeding into the brain among the 500 enrolled patients. However, the analysis’ results showed neither of the two blood thinners improved outcomes among the stroke survivors.

Using the utility-weighted mRS scale, those receiving placebo averaged 6.8, while those receiving argatroban and eptifibatide averaged 5.2 and 6.3, respectively. Investigators noted the types of disability tend to vary, but those with a utility-weighted mRS scale of 6 often have trouble performing daily activities without assistance or support.

Further studies are ongoing for those undergoing thrombectomy to determine whether blood thinners delivered into the affected artery may improve outcomes versus the medication provided through a vein.

“We were not able to address the possible benefit of giving these or similar blood thinners directly into an artery in the area of the stroke, rather than giving the medications systematically through a vein, as done in this trial,” Adeoye added.2


  1. Adeoye OM, Broderick JP, Derdeyn CP, Grotta JC, Pizzella SR, Barreto AD. Multi-Arm Optimization of Stroke Thrombolysis (MOST) Trial. Presented at the American Stroke Association’s International Stroke Conference 2024. February 7 - 9, 2024.
  2. Blood thinners added to clot-busting medication did not improve stroke outcomes. American Heart Association. February 7, 2024. Accessed February 7, 2024.