Preclinical Evaluation of a Zotarolimus-Eluting Stent for Intracranial Application: A 30-Day GLP Canine Study

BackgroundZotarolimus-Eluting Stents (ZES) are increasingly used off-label for intracranial atherosclerotic disease (ICAD). However, foundational, Good Laboratory Practice (GLP) compliant preclinical safety data specific to the cerebral vasculature is lacking. Therefore, we conducted the first systematic evaluation of the technical feasibility, anatomic features, and 30-day clinical safety profile of the Onyx Frontier ZES (Medtronic, Minneapolis, MN) in a GLP-compliant canine intracranial model. MethodsIn a prospective GLP study, a 2.0 x 8.0 mm Onyx Frontier ZES was implanted in the basilar artery of twelve healthy mongrel canines pre-treated with dual antiplatelet therapy. Vertebral artery tortuosity was assessed via angiography and graded as Type I (non-tortuous/straight), Type II (moderately tortuous/S-shaped), or Type III (severely tortuous/coiled). The primary endpoints were procedural success and 30-day safety, assessed via angiography, serial neurological examinations, and comprehensive clinical monitoring. ResultsTechnical success was achieved in 100% of animals (12/12). The cohort exhibited challenging anatomy, with a mean basilar artery diameter of 1.39 {+/-} 0.10 mm. Tortuosity analysis revealed that 33.3% of animals were Type I (mild), 58.3% were Type II (moderate), and 8.3% were Type III (severe). Post-procedure, mild vasospasm was observed in all cases, with only one canine requiring intra-arterial verapamil. A single case (8.3%) of self-limiting contrast extravasation occurred without clinical sequelae. At 30 days, there was no mortality, and no animals suffered a neurological adverse event. Minor clinical events were unrelated to the device, and comprehensive clinical pathology panels revealed no evidence of systemic toxicity or a significant inflammatory response. ConclusionThis first-of-its-kind preclinical study demonstrates that implantation of the Onyx Frontier ZES is technically feasible with a 100% success rate in a sub-2mm vessel model with significant tortuosity and has an excellent 30-day safety profile with no clinical evidence of neurotoxicity. These findings provide foundational preclinical data supporting further investigation of this technology for treating ICAD in human subjects.