Effect of Intravenous Tirofiban vs Placebo Before Endovascular Thrombectomy on Functional Outcomes in Large Vessel Occlusion Stroke: The RESCUE BT Randomized Clinical Trial.

Importance: Tirofiban is a highly selective nonpeptide antagonist of glycoprotein IIb/IIIa receptor, which reversibly inhibits platelet aggregation. It remains uncertain whether intravenous tirofiban is effective to improve functional outcomes for patients with large vessel occlusion ischemic stroke undergoing endovascular thrombectomy. Objective: To assess the efficacy and adverse events of intravenous tirofiban before endovascular thrombectomy for acute ischemic stroke secondary to large vessel occlusion. Design, Setting, and Participants: This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 55 hospitals in China, enrolling 948 patients with stroke and proximal intracranial large vessel occlusion presenting within 24 hours of time last known well. Recruitment took place between October 10, 2018, and October 31, 2021, with final follow-up on January 15, 2022. Interventions: Participants received intravenous tirofiban (n = 463) or placebo (n = 485) prior to endovascular thrombectomy. Main Outcomes and Measures: The primary outcome was disability level at 90 days as measured by overall distribution of the modified Rankin Scale scores from 0 (no symptoms) to 6 (death). The primary safety outcome was the incidence of symptomatic intracranial hemorrhage within 48 hours. Results: Among 948 patients randomized (mean age, 67 years; 391 [41.2%] women), 948 (100%) completed the trial. The median (IQR) 90-day modified Rankin Scale score in the tirofiban group vs placebo group was 3 (1-4) vs 3 (1-4). The adjusted common odds ratio for a lower level of disability with tirofiban vs placebo was 1.08 (95% CI, 0.86-1.36). Incidence of symptomatic intracranial hemorrhage was 9.7% in the tirofiban group vs 6.4% in the placebo group (difference, 3.3% [95% CI, -0.2% to 6.8%]). Conclusions and Relevance: Among patients with large vessel occlusion acute ischemic stroke undergoing endovascular thrombectomy, treatment with intravenous tirofiban, compared with placebo, before endovascular therapy resulted in no significant difference in disability severity at 90 days. The findings do not support use of intravenous tirofiban before endovascular thrombectomy for acute ischemic stroke. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR-IOR-17014167.

Predictors of unexplained early neurological deterioration after thrombectomy for posterior circulation infarction: a reanalysis of the BASILAR study.

OBJECTIVE: The efficacy of endovascular thrombectomy in patients with posterior circulation ischemic stroke remains controversial. Early neurological deterioration (END) as an important predictor of poor outcome is poorly understood, except in cases of symptomatic intracranial hemorrhage, recanalization failure, and malignant cerebral edema. The objective of this study was to assess predictors of unexplained END (UnEND) after endovascular thrombectomy. METHODS: The BASILAR study is a multicenter prospective observational study in which 647 patients with vertebrobasilar occlusion on imaging within 24 hours of stroke onset and who underwent endovascular treatment were enrolled, of whom 477 who had undergone successful recanalization were included in this study. Multivariate analysis was used to identify the predictors of UnEND, defined as a ≥ 4-point increase in National Institutes of Health Stroke Scale (NIHSS) score at 24 hours after endovascular thrombectomy. RESULTS: Among the 477 eligible patients included, UnEND occurred in 86 (18%) patients. The predictors of UnEND were stress hyperglycemic ratio (SHR) (OR 2.2, 95% CI 1.1-4.6; p = 0.031), baseline NIHSS score (OR 0.9, 95% CI 0.83-0.95; p = 0.001), and asymptomatic intracerebral hemorrhage (aICH) (OR 5.9, 95% CI 1.7-20.0; p = 0.004). The occurrence rate of a favorable outcome, defined as a modified Rankin Scale score of 0-3 at 90 days, was lower in the UnEND group (5.8% vs 47.6%, p < 0.001) compared with the group without END, and the UnEND group had higher mortality at 90 days (66.3% vs 27.4%, p < 0.001). CONCLUSIONS: UnEND may be associated with poor outcome after endovascular thrombectomy in patients with acute vertebrobasilar occlusion. Some modifiable factors such as SHR and aICH could be targeted to improve the efficacy of endovascular thrombectomy.

Association of Tirofiban With Functional Outcomes After Thrombectomy in Acute Ischemic Stroke Due to Intracranial Atherosclerotic Disease.

BACKGROUND AND OBJECTIVE: To investigate the efficacy and safety of IV infusion of tirofiban before endovascular thrombectomy for patients with large vessel occlusion due to intracranial atherosclerotic disease. The secondary objective was to identify potential mediators for the clinical effect of tirofiban. METHODS: Post hoc exploratory analysis of the Endovascular Treatment With versus Without Tirofiban for Patients with Large Vessel Occlusion Stroke (RESCUE BT) trial, which was a randomized, double-blinded, placebo-controlled trial at 55 centers in China from October 2018 to October 2021. Patients with occlusion of the internal carotid artery or middle cerebral artery due to intracranial atherosclerosis were included. The primary efficacy outcome was the proportion of patients achieving functional independence (defined as modified Rankin scale 0-2) at 90 days. Binary logistic regression and causal mediation analyses were used to estimate the treatment effect of tirofiban and the potential mediators. RESULTS: This study included 435 patients, of whom 71.5% were men. The median age was 65 (interquartile range [IQR] 56-72) years, with a median NIH Stroke Scale of 14 (IQR 10-19). Patients in the tirofiban group had higher rates of functional independence at 90 days than patients in the placebo group (adjusted odds ratio 1.68; 95% CI 1.11-2.56, p = 0.02) without an increased risk of mortality or symptomatic intracranial hemorrhage. Tirofiban was associated with fewer thrombectomy passes (median [IQR] 1 [1-2] vs 1 [1-2], p = 0.004), which was an independent predictor of functional independence. Mediation analysis showed tirofiban-reduced thrombectomy passes explained 20.0% (95% CI 4.1%-76.0%) of the effect of tirofiban on functional independence. DISCUSSION: In this post hoc analysis of the RESCUE BT trial, tirofiban was an effective and well-tolerated adjuvant medication of endovascular thrombectomy for patients with large vessel occlusion due to intracranial atherosclerosis. These findings need to be confirmed in future trials. TRIAL REGISTRATION INFORMATION: The RESCUE BT trial was registered on the Chinese Clinical Trial Registry: chictr.org.cn, ChiCTR-INR-17014167. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that tirofiban plus endovascular therapy improves 90-day outcome for patients with large vessel occlusion due to intracranial atherosclerosis.

Effect of vertebrobasilar dolichoectasia on endovascular therapy in acute posterior circulation infarction.

Background and purpose: This study aimed to analyze the feasibility and safety of endovascular therapy (EVT) in patients with acute posterior circulation stroke and vertebrobasilar dolichoectasia (VBD). Materials and methods: BASILAR was a national prospective registry of consecutive patients with symptomatic and imaging-confirmed acute stroke in the posterior circulation within 24 h of symptom onset. We evaluated EVT feasibility and safety in patients with VBD. Primary outcomes included improvement in modified Rankin Scale scores (mRS) at 90 days and mortality within 90 days. The secondary outcome was the rate of favorable functional outcome, defined as mRS ≤ 3 (indicating independent ambulation) at 90 days. Safety outcomes included surgery-related complications and other serious adverse events. Results: A total of 534 cases were included: 159 with VBD and 375 controls. No significant difference in mRS at 90 days was found between groups, but patients with VBD had a higher baseline National Institutes of Health Stroke Scale (NIHSS) score [30 (19-33) vs. 25 (15-32)] and were older [65 (59-74) vs. 63 (55-72) year]. After propensity score matching, there were no significant differences in baseline NIHSS score between the two groups, and the efficacy and safety of EVT were similar between patients with or without VBD. Furthermore, the prognostic effect of puncture-to-recanalization time on the probability of mortality within 90 days in EVT-treated patients with VBD was significant {adjusted odds ratio, 1.008 [95% confidence interval (1.001-1.015)]}. Conclusion: Endovascular therapy is safe and feasible in patients with acute posterior circulation stroke and VBD. The puncture-to-recanalization time is important for predicting the prognosis of EVT-treated patients with VBD.

Impact of Body Temperature in Patients With Acute Basilar Artery Occlusion: Analysis of the BASILAR Database.

Background: A link between body temperature and stroke outcomes has been established but not for acute basilar artery occlusion. We aimed to determine the association between body temperature and clinical outcomes in patients with acute basilar artery occlusion and temperature management range. Methods: We included patients from the Endovascular Treatment for Acute Basilar Artery Occlusion Study (BASILAR) database with records of both admission body temperature (ABT) and peak body temperature (PBT). ABT was defined as the body temperature first measured at the hospital visit, PBT was defined as the highest temperature within 24 h of treatment, and minus body temperature (MBT) was defined as PBT-ABT. The primary clinical outcome was favorable functional outcome, defined as the proportion of patients with a modified Rankin Scale score of 0-3 at 3 months. Secondary outcomes included 3-month mortality, in-hospital mortality, and symptomatic cerebral hemorrhage. Results: A total of 664 patients were enrolled in the study; 74.7% were men, with a median age of 65 (interquartile range, 57.25-74) years. In all patients, multivariate analysis indicated that PBT and MBT were independent predictors of favorable functional outcome [odds ratio (OR), 0.57 (95% CI, 0.43-0.77); OR, 0.68 (95% CI, 0.52-0.88), respectively], and higher ABT, PBT, and MBT were associated with an increased 3-month mortality [OR, 1.47 (95% CI, 1.03-2.10), OR, 1.58 (95% CI, 1.28-1.96), OR, 1.35 (95% CI, 1.11-1.65), respectively]. Proportional odds models demonstrated that when ABT, PBT, MBT were in the range of <37.5, <38.9, and -0.6-2.7°C, respectively, the benefit of the endovascular treatment is clearly greater than that of standard medical treatment in terms of favorable functional outcome. Conclusions: Body temperature is an independent predictor of clinical outcome in patients with acute basilar artery occlusion. It is necessary to control the patient body temperature within the appropriate range in clinical settings. Trial Registration: Chinese Clinical Trial Registry ChiCTR1800014759. Registered 03 February 2018. Retrospectively registered.