Efficacy of Adjunctive Therapies for Acute Ischemic Stroke Based on Phase 3 MOST Trial: Opeolu Adeoye, MD, MS; Andrew Barerrto, MD, MS

WATCH TIME: 3 minutes

“We designed the trial to answer the question for both medications, which we are pleased with in terms of getting to a definitive answer for these 2 drugs in one trial as opposed to 2 separate trials. We also designed it so that we could at various points look at the data to see the likelihood of these drugs improving disability after stroke.”

In stroke care, treatment options including intravenous thrombolysis and mechanical thrombectomy have changed the landscape of care for acute ischemic stroke (AIS) although there is a need for more options for patients.¹ Two potential approaches of adjunctive intravenous medications that could be administered in the clinical setting for AIS are argatroban, a direct thrombin inhibitor, and eptifibatide (Integrillin; Millennium Pharmaceuticals), an antiplatelet drug of the glycoprotein IIb/IIIa inhibitor class.² Despite being underpowered, findings from previous phase 2 trials suggest that the combination of these therapies have a favorable direction of effect with no increased safety.³

In a recent analysis of the phase 3, randomized controlled MOST trial (NCT03735979) assessing argatroban or eptifibatide, findings showed that both treatments failed efficacy in reducing disability in patients with AIS treated with thrombolysis within 3 hours of symptom onset.⁴The findings were presented at the 2024 International Stroke Conference (ISC), held February 7-9, in Phoenix, Arizona, by lead author Opeolu Adeoye, MD, MS, professor of emergency medicine at the Washington University in St. Louis, and senior author Andrew Barerrto, MD, MS, associate professor of neurosurgery, McGovern Medical School at UTHealth Houston.

During the meeting, the duo sat down with NeurologyLive® in an interview to provide an overview of the methods of the trial and further discuss the findings. Adeoye spoke about the reasons behind the unexpected negative impact of the adjunctive therapies in poststroke patients while Barerrto talked about how the trial’s prespecified design contributes to the understanding of the medications' efficacy. Both experts also shared their thoughts on the trial's limitations and their reactions to any surprising results uncovered in the analysis. In addition, Adeoye and Barerrto talked about the next steps for researchers in exploring alternative approaches to enhance thrombolysis performance.

Click here for more coverage of ISC 2024.

REFERENCES
1. Chlorogiannis DD, Mavridis T, Adamou A, et al. Argatroban as an Add-On to rtPA in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis. J Clin Med. 2024;13(2):563. Published 2024 Jan 18. doi:10.3390/jcm13020563
2. Deeds SI, Barreto A, Elm J, et al. The multiarm optimization of stroke thrombolysis phase 3 acute stroke randomized clinical trial: Rationale and methods. Int J Stroke. 2021;16(7):873-880. doi:10.1177/1747493020978345
3. Berekashvili K, Soomro J, Shen L, et al. Safety and Feasibility of Argatroban, Recombinant Tissue Plasminogen Activator, and Intra-Arterial Therapy in Stroke (ARTSS-IA Study). J Stroke Cerebrovasc Dis. 2018;27(12):3647-3651. doi:10.1016/j.jstrokecerebrovasdis.2018.08.036
4. Adeoye OM, Joseph P Broderick, Colin P Derdeyn, et al. Multi-Arm Optimization of Stroke Thrombolysis (MOST) Trial. Presented at: International Stroke Conference; February 7-9, 2024; Abstract LB3.