A recent clinical trial has found that adding anti-clotting drugs to standard stroke care does not improve patient outcomes. The Multi-arm Optimization of Stroke Thrombolysis (MOST) trial, conducted at 57 sites across the U.S., evaluated the efficacy of argatroban and eptifibatide, when added to routine intravenous thrombolysis, in preventing new blood clots in stroke patients. The study, led by Opeolu Adeoye, MD, head of the Department of Emergency Medicine at Washington University School of Medicine in St. Louis, was published in The New England Journal of Medicine on September 4, 2024.
Study Design and Findings
The MOST trial aimed to address the issue of recurrent blood clots in stroke patients who have already received vessel-clearing interventions. Patients were randomly assigned to receive either argatroban, eptifibatide, or a placebo, in addition to intravenous thrombolysis. A checkpoint was set at 500 patients to assess treatment efficacy. However, data analysis revealed that neither drug met the pre-defined efficacy threshold.
"We're a little disappointed in the results," said Adeoye. "But it's meaningful to optimal patient care that we've answered the question definitively. Neither of the drugs helps prevent further clots."
The probability of either drug being helpful was less than 1%. Furthermore, argatroban and eptifibatide were associated with greater incidences of disability and mortality within the three-month post-treatment observation window. Although safety monitors found that deaths appeared unrelated to the medications, the lack of improvement compared to the placebo led to the trial's discontinuation.
Implications for Stroke Treatment
Despite the negative results, researchers emphasize the importance of such trials in advancing medical knowledge. Peter Panagos, MD, professor of emergency medicine and co-author of the study, noted, "Without negative trials, we would not know how to design new trials. Future success is built upon the hard work of previous research effort."
Currently, treatment options for stroke patients are limited. While some undergo clot removal procedures or receive intravenous thrombolysis, a significant number still experience disabilities. "Even with those treatments, over half of patients still have a significant disability three months after their stroke," Adeoye explained. The trial sought to prevent clot reformation, a common cause of worsening or persistent stroke symptoms.
Future Directions
While argatroban and eptifibatide did not prove effective in this context, Adeoye indicated that research continues, with drugs in development targeting different aspects of blood coagulation and clotting. Alternative delivery methods, such as direct arterial delivery, may also enhance drug efficacy.
Panagos highlighted the role of WashU Medicine in leading stroke research, benefiting the 1,700 stroke patients treated annually at Barnes-Jewish Hospital. "Because we are involved in and lead most of the key basic science and clinical research for stroke and cerebrovascular patients nationally and internationally, we can bring the latest interventions to our patients in St. Louis and help advance treatment and prevention strategies," Panagos said.
