Stroke patients who experience a blood clot of their brain blood vessels are vulnerable to recent blockages during recovery, even in the event that they receive interventions to clear the vessels. To avoid further clots, doctors at 57 U.S. facilities have been testing a possible solution: adding anticoagulant drugs to clot-busting drugs.

But results from a clinical trial led by Dr. Opeolu Adeoye, chairman of the Department of Emergency Medicine at Washington University School of Medicine in St. Louis, show that two such drugs don’t improve outcomes.

Results shall be available on September 4th Recent England Medical Journal.

“We’re a little bit disillusioned with the outcomes,” said Adeoye, who can be a distinguished professor of emergency medicine at BJC HealthCare. “But what’s vital for optimal patient care is that we’ve answered that query definitively. Neither drug helps prevent further clots.”

The Multi-arm Optimization of Stroke Thrombolysis (MOST) trial, led by Adeoye, was designed to check the effectiveness of adding argatroban, a blood-thinning drug, or eptifibatide, which prevents platelets from clumping, to routine intravenous thrombolytic therapy.

The study closed the chapter on the potential use of those drugs, but Dr. Peter Panagos, professor of emergency medicine and study co-author, said such efforts have implications for future medical advances, including potential recent anticoagulant treatments.

Without negative trials, we would not know the best way to design recent trials. Future success builds on the labor of previous research efforts.”

Dr. Peter Panagos, professor of emergency medicine and study co-author

Doctors don’t have many treatment options for stroke patients. Some patients undergo surgery to remove the clot. Others receive intravenous thrombolysis to free the affected blood vessel by delivering a clot-dissolving drug into the bloodstream. Many patients receive each interventions.

“Even with these treatments, greater than half of patients still have significant disability three months after their stroke,” said Adeoye, who sees patients at Barnes-Jewish Hospital and Missouri Baptist Medical Center and in addition provides teleconsultation for stroke. “After thrombolysis, the clot can reform, which might worsen or persist the stroke.”

Stopping these clots from forming with additional treatment with anticoagulant drugs appeared like a promising idea, especially since there are FDA-approved medications that previous studies have shown could also be effective.

Within the MOST trial, patients were randomly assigned to receive argatroban, eptifibatide, or placebo. Adeoye explained that the study had built-in checkpoints to make sure that the treatment outcomes met efficacy thresholds so it could proceed. The primary checkpoint was set at 500 patients, which the team achieved in 2023.

“After we checked out the info, it was clear to us that not one of the drugs would even come near our threshold,” he said.

The truth is, the probability that either drug was helpful was lower than 1%. Worse, argatroban and eptifibatide were related to higher rates of disability and mortality in the course of the three-month follow-up period after treatment ended.

This correlation was not necessarily alarming; the project’s safety monitors said the causes of death appeared unrelated to the drugs. The shortage of improvement seen with the drugs over that seen with placebo was reason enough to terminate the study.

There are more options to think about to enhance stroke outcomes. Adeoye said there are drugs in development that focus on different parts of the blood clotting and coagulation processes that will prove more practical than argatroban or eptifibatide, in addition to other procedures, akin to direct injection into an artery, where such drugs could also be more practical.

Panagos, who directs the brand new Neurological Emergencies Section within the Department of Emergency Medicine, added that WashU Medicine’s leadership in any such research advantages the 1,700 stroke patients treated by WashU Medicine physicians at Barnes-Jewish Hospital every year.

“Because we’re involved in and conduct many of the key basic and clinical research for stroke and cerebrovascular disease patients nationally and internationally, we are able to provide our patients in St. Louis with the newest interventions and help advance treatment and prevention strategies,” Panagos said. “Our commitment to clinical research helps provide our community with the very best quality, most progressive treatments.”

Adeoye O, Broderick J, Derdeyn CP, Grotta JC, Barsan W, Bentho O, Berry S, Concha M, Davis I, Demel S, Elm J, Gentile N, Graves T, Hoffman M, Huang J, English J, Janis[ Bezpłatny artykuł PMC ][ PubMed ]Brilliant S, Brilliant AS, Khatri P, Levine SR, Majjhoo A, Pancioli A, Panagos P, Pizzella S, Ranasinghe T, Sabagha N, Sivakumar S, Streib C, Vagal A, Wilson A, Wintermark M, Yoo AJ, Barreto AD. Adjunctive intravenous argatroban or eptifibatide within the treatment of ischemic stroke. Recent England Journal of Medicine. September 4, 2024