Introduction Intracranial atherosclerotic disease (ICAD) is a major cause of stroke and presents a unique challenge with a high rate of reocclusion following mechanical thrombectomy, leading to less favorable clinical outcomes. When standard thrombectomy is unsuccessful, rescue treatments for persistent ICAD-related occlusion or stenosis are needed. Among the available options, glycoprotein inhibitors have shown promise as a potential therapeutic strategy in the setting of ICAD. This systematic review examines studies that explore the use of glycoprotein inhibitors as an acute standalone post-EVT rescue treatment for refractory occlusion or high-grade stenosis in the setting of ICAD stroke.

Methods Databases searched, including Embase, Pubmed, and Medline from the date of conception through March 1st, 2023. We included studies using GPI as the first-line rescue treatment after failed thrombectomy or in the setting with high-grade stenosis (>50%) at risk of re-occlusion. We included both single and two-arm studies. Abstracts, case reports, and studies of 10 or less patients were excluded. A basic model (BM) analysis consisting of a simple odds ratio (OR) analysis was conducted on both two arm and single arm studies. An in-depth meta-analysis of two arm studies was conducted using the random-effects model (REM) and reported logarithmic odds ratios (LORs) and 95% CIs. The primary outcome of interest was good clinical outcomes (defined as a modified Rankin Scale (mRS) score of 0-2 at 90 days). Secondary outcomes of interest were successful recanalization (TICI 2b-3), symptomatic intracranial hemorrhage (sICH), and mortality by 90 days.

Results We screened a total of 2,639 articles. We included a total of seven studies in our analysis, four of which were two arm studies for a total of 735 cases, 455 of which were GPI-only rescue and 279 non-GPI-only rescue. All studies utilized intraarterial GPI delivery with several also included an extended intravenous delivery drip. Non-GPI-only arms included rescue stenting/angioplasty with and without GPI, and no-rescue treatment. Clinical outcomes were significantly in favor of GPI with both BM (OR = 1.54, 1.14 - 2.08) and REM (LOR = 0.52 (0.12 - 0.93) favoring GPI. Recanalization was significantly better for GPI rescue using BM (OR = 3.837, 95% CI: 2.28 - 6.46), but was not significant with REM analysis (LOR = 1.04, -0.36 - 2.44). No difference sICH was demonstrated with BM (OR = 0.6, 0.25-1.44) or REM (LOR = -0.07, -1.20 - 1.06). Mortality rate was significantly lower for the GPI rescue group with both BM (OR = 0.452, 95% CI: 0.27-0.74) and REM (LOR = -1.16, -1.80 - -0.51).

Conclusion These findings highlight the potential value of GPIs as a viable first line therapy for EVT rescue therapy in the setting of ICAD. This study was limited by the nature of the literature, which were non-randomized observational studies. Randomized controlled trials are needed to validate and refine our understanding of the role of GPIs in the management of refractory or re-occlusive ICAD stroke.

Disclosures A. Brake: None. C. Heskett: None. K. Le: None. L. Fry: None. M. Abraham: 2; C; Stryker.