Unmet Needs in Acute Ischemic Stroke: Overcoming Recalcitrant Clots

Endovascular thrombectomy has revolutionized acute ischemic stroke treatment, significantly improving recanalization rates. However, up to 20% of cases involve recalcitrant clots that fail to recanalize or require multiple passes, negatively impacting clinical outcomes. This review explores the multifaceted nature of these challenging clots, including insights from preclinical, imaging, and clinical studies, with strategies to overcome them. Ex-vivo clot characterization reveals red blood cell-poorness in clots as a common feature in fibrin-rich, platelet-rich, neutrophil extracellular traps-rich, collagenous or bacteria-rich clots. Preclinical models have evolved alongside ex-vivo clot analysis, demonstrating properties such as increased stiffness, toughness, hardness, and stickiness that hinders retrieval. Imaging markers such as absence of the hyperdense artery sign or susceptibility vessel sign correlate with recalcitrant clots, although reliable predictors of recalcitrant clots remain elusive. Recent innovations, including specifically designed tough clot stent-retrievers such as Nimbus and technologies to improve complete clot ingestion such as super-bore aspiration catheters and cyclic aspiration have shown promise. Yet, a substantial proportion of cases still have difficulty or fail to achieve recanalization. Techniques such as rescue stenting and dual-stent-retriever approaches offer additional strategies but carry risks of vascular injury and complications. Major research limitations include clot deformation during retrieval and the inability to remove some clots. Furthermore, some interactions are poorly understood, such as the biological interaction between the clot and vessel wall or with circulating thrombo-influencing proteins. Overcoming these challenges can pave the pathway for creative solutions to elegantly improve the recanalization of tough clots.