Clinical study of tirofiban compared to low molecular weight heparin in the antithrombotic treatment of progressive pontine infarction.

OBJECTIVE: To investigate the efficacy and safety of tirofiban and low molecular weight heparin (LMWH) in the treatment of patients undergoing acute progressive pontine infarction. PATIENTS AND METHODS: Patients with acute progressive pontine infarction who were hospitalized in the Neurology Department from June 2021 to June 2023 were included in the study and randomly divided into two groups, namely the experimental group (tirofiban group) and the control group (LMWH group). All patients in both groups were required to receive conventional comprehensive treatment and dual antiplatelet therapy with aspirin + clopidogrel at the beginning of admission. The National Institutes of Health Stroke Scale (NIHSS) score and Barthel Index (BI) were used to evaluate the neurological deficits on the first day of admission, the next day with stroke progression, and at discharge after treatment with tirofiban and LMWH, respectively in the two groups. The modified Rankin Scale was employed to assess prognosis on the 90th day after treatment. Clinical adverse events were followed up for 90 days, comparing the clinical efficacy and safety of the two treatment methods. RESULTS: There was no statistical significance in NIHSS score and Barthel Index between the tirofiban group and the LMWH group on the first day of admission and the next day with stroke progression (p > 0.05). After stroke progression, tirofiban and LMWH were separately used for treatment in the two groups. We found that the NIHSS score of the tirofiban group was lower than that of the LMWH group, and the Barthel Index score was higher than that of the LMWH group at discharge (p < 0.05). After three months of follow-up, the mRS score of the tirofiban group was dramatically higher than that of the LMWH group (p < 0.05). No significant harmful or adverse reactions, such as bleeding events, were found in the two groups (p > 0.05). CONCLUSIONS: Tirofiban may be more effective and safer than LMWH in controlling the progression of acute pontine infarction, but further and large-sample studies are still needed to confirm this finding.

Efficacy and Safety of Tirofiban Before Stenting for Symptomatic Intracranial Atherosclerotic Stenosis: A Randomized Clinical Trial.

BACKGROUND AND OBJECTIVES: Acute stent thrombosis (AST) is not uncommon and even catastrophic during intracranial stenting angioplasty in patients with symptomatic high-grade intracranial atherosclerotic stenosis (ICAS). The purpose of this study was to investigate whether adjuvant intravenous tirofiban before stenting could reduce the risk of AST and periprocedural ischemic stroke in patients receiving stent angioplasty for symptomatic ICAS. METHODS: A prospective, multicenter, open-label, randomized clinical trial was conducted from September 9, 2020, to February 18, 2022, at 10 medical centers in China. Patients intended to receive stent angioplasty for symptomatic high-grade ICAS were enrolled and randomly assigned to receive intravenous tirofiban or not before stenting in a 1:1 ratio. The primary outcomes included the incidence of AST within 30 minutes after stenting, periprocedural new-onset ischemic stroke, and symptomatic intracranial hemorrhage. The outcomes were analyzed using logistic regression analysis to obtain an odds ratio and 95% confidence interval. RESULTS: A total of 200 participants (122 men [61.0%]; median [interquartile ranges] age, 57 [52-66] years) were included in the analysis, with 100 participants randomly assigned to the tirofiban group and 100 participants to the control (no tirofiban) group. The AST incidence was lower in the tirofiban group than that in the control group (4.0% vs 14.0%; adjusted odds ratio, 0.25; 95% CI 0.08-0.82; p = 0.02). No significant difference was observed in the incidence of periprocedural ischemic stroke (7.0% vs 8.0%; p = 0.98) or symptomatic intracranial hemorrhage between the 2 groups. DISCUSSION: This study suggests that adjuvant intravenous tirofiban before stenting could lower the risk of AST during stent angioplasty in patients with symptomatic high-grade ICAS. TRIAL REGISTRATION INFORMATION: URL: chictr.org.cn; Unique identifier: ChiCTR2000031935. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with symptomatic high-grade ICAS, pretreatment with tirofiban decreases the incidence of acute stent thrombosis. This study is Class II due to the unequal distribution of involved arteries between the 2 groups.

Adjunct Intraarterial or Intravenous Tirofiban Versus No Tirofiban After Successful Recanalization of Basilar Artery Occlusion Stroke: The BASILAR Registry.

BACKGROUND: Approximately half of patients who achieve successful reperfusion do not achieve functional independence. The present study sought to investigate the clinical outcomes and safety of intraarterial or intravenous tirofiban as adjunct therapy in patients with acute basilar artery occlusion who had achieved successful recanalization with endovascular treatment. METHODS AND RESULTS: In the national, prospective BASILAR (Endovascular Treatment for Acute Basilar Artery Occlusion Study) registry, 458 patients who met inclusion criteria were divided into 3 groups based on tirofiban administration (no tirofiban, n=262; intravenous tirofiban, n=101; intraarterial+intravenous tirofiban, n=95). Their clinical outcomes were compared with 90-day modified Rankin Scale scores. Adjusted odds ratios (aORs) and 95% CIs were obtained by logistic regression models and propensity score matching. Safety outcomes included any intracranial hemorrhage (ICH), symptomatic ICH, and mortality. Among 458 included patients, 184 (40.2%) achieved a favorable outcome (modified Rankin Scale score 0-3). There were no differences between the intravenous tirofiban group and the no tirofiban group in terms of safety and clinical outcomes (all P>0.05). Compared with the no tirofiban group, the intraarterial+intravenous tirofiban group had higher odds of 90-day modified Rankin Scale score 0 to 3 (aOR, 2.44 [95% CI, 1.30-4.64], P=0.006) and lower 3-month mortality (aOR, 0.38 [95% CI, 0.19-0.71], P=0.002) without an increase in any ICH (aOR, 0.34 [95% CI, 0.09-1.01], P=0.07) or symptomatic ICH (aOR, 0.23 [95% CI, 0.03-0.90], P=0.05). Similar results of intraarterial+intravenous tirofiban on improving clinical outcomes were detected in novel cohorts constructed by propensity score matching. CONCLUSIONS: Intraarterial+intravenous rather than intravenous tirofiban improved clinical outcomes without increasing the frequency of symptomatic ICH among patients with basilar artery occlusion after successful endovascular treatment. Further studies are needed to delineate the roles of intraarterial+intravenous tirofiban in patients with basilar artery occlusion receiving endovascular treatment.

Intravenous Tirofiban Versus Alteplase Before Endovascular Treatment in Acute Ischemic Stroke: A Pooled Analysis of the DEVT and RESCUE BT Trials.

BACKGROUND: The present study aimed to evaluate the efficacy and safety of intravenous tirofiban versus alteplase before endovascular treatment (EVT) in acute ischemic stroke patients with intracranial large vessel occlusion. METHODS: This was a post hoc analysis using data from 2 multicenter, randomized trials: the DEVT trial (Direct Endovascular Treatment for Large Vessel Occlusion Stroke) from May 2018 to May 2020 and the RESCUE BT trial (Intravenous Tirofiban Before Endovascular Thrombectomy for Acute Ischemic Stroke) from October 2018 to October 2021. Patients with acute intracranial large vessel occlusion within 4.5 hours from last known well were dichotomized into 2 groups: tirofiban plus EVT versus alteplase bridging with EVT. The primary outcome was functional independence (modified Rankin Scale score of 0-2) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage and 3-month mortality. Multivariable logistic regression (adjusting for baseline systolic blood pressure, occlusion site, onset-to-puncture time, anesthesia, and first choice of EVT) and propensity score overlap weighting (balance in demographic covariates, stroke characteristics, and initial management between groups) were performed. RESULTS: One-hundred and eighteen alteplase-treated patients in the DEVT trial and 98 tirofiban-treated patients in the RESCUE BT trial were included (median age, 70 years; 115 [53.2%] men). The rate of functional independence was 60.2% in the tirofiban group compared with 46.6% in the alteplase group (adjusted odds ratio, 1.25 [95% CI, 0.60-2.63]). Compared with alteplase, tirofiban was not associated with increased risk of symptomatic intracranial hemorrhage (6.8% versus 9.2%; P=0.51) and mortality (17.8% versus 19.4%; P=0.76). The propensity score overlap weighting analyses showed consistent outcomes. CONCLUSIONS: Among patients with intracranial large vessel occlusion within 4.5 hours of onset, tirofiban plus EVT was comparable to alteplase bridging with EVT regarding the efficacy and safety outcomes. These findings should be interpreted as preliminary and require confirmation in a randomized trial. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifiers: ChiCTR-IOR-17013568 and ChiCTR-INR-17014167.

Cost-effectiveness of tirofiban for acute ischemic stroke without large or medium-sized vessel occlusion: A Markov modelling analysis from the Chinese and United States perspectives.

BACKGROUND: The RESCUE BT2 trial recently showcased the efficacy of tirofiban in treating acute ischemic stroke (AIS) without large or medium-sized vessel occlusion. To further assess the value of tirofiban from the perspectives of Chinese and US healthcare system, a study was conducted to evaluate its cost-effectiveness. METHODS: A hybrid model, integrating a short-term decision tree with a long-term Markov model, was developed to assess cost-effectiveness between tirofiban and aspirin for stroke patients without large or medium-sized vessel occlusion. Efficacy data for tirofiban was sourced from the RESCUE BT2 trial, while cost information was derived from published papers. Outcomes measured included respective cost, effectiveness, and incremental cost-effectiveness ratio (ICER). We conducted a one-way sensitivity analysis to assess the robustness of the results. Additionally, we performed probabilistic sensitivity analysis (PSA) through 10,000 Monte Carlo simulations to evaluate the uncertainties associated with the results. RESULTS: The study revealed that tirofiban treatment in AIS patients without large or medium-sized vessel occlusion led to a considerable reduction of 2141 Chinese Yuan (CNY) in total cost, along with a lifetime gain of 0.14 quality-adjusted life years (QALYs). In the US settings, tirofiban also exhibited a lower cost ($197,055 versus $201,984) and higher effectiveness (4.15 QALYs versus 4.06 QALYs) compared to aspirin. One-way sensitivity analysis revealed that post-stroke care costs and stroke utility had the greatest impact on ICER fluctuation in both Chinese and US settings. However, these variations did not exceed the willingness-to-pay threshold. PSA demonstrated tirofiban's superior acceptability over aspirin in over 95% of potential scenarios. CONCLUSION: Tirofiban treatment for AIS without large or medium-sized vessel occlusion appeared dominant compared to aspirin in both China and the US.

Statistical analysis plan for the multicenter, open, randomized controlled clinical trial to assess the efficacy and safety of intravenous tirofiban vs aspirin in acute ischemic stroke due to tandem lesion, undergoing recanalization therapy by endovascular treatment (ATILA trial).

RATIONALE: In-stent reocclusion after endovascular therapy has a negative impact on outcomes in acute ischemic stroke (AIS) due to tandem lesions (TL). Optimal antiplatelet therapy approach in these patients to avoid in-stent reocclusion is yet to be elucidated. AIMS: To assess efficacy and safety of intravenous tirofiban versus intravenous aspirin in patients undergoing MT plus carotid stenting in the setting of AIS due to TL. SAMPLE SIZE ESTIMATES: Two hundred forty patients will be enrolled, 120 in every treatment arm. METHODS AND DESIGN: A multicenter, prospective, randomized, controlled (aspirin group), assessor-blinded clinical trial will be conducted. Patients fulfilling the inclusion criteria will be randomized at MT onset to the experimental or control group (1:1). Intravenous aspirin will be administered at a 500-mg single dose and tirofiban at a 500-mcg bolus followed by a 200-mcg/h infusion during the first 24 h. All patients will be followed for up to 3 months. STUDY OUTCOMES: Primary efficacy outcome will be the proportion of patients with carotid in-stent thrombosis within the first 24 h after MT. Primary safety outcome will be the rate of symptomatic intracranial hemorrhage. DISCUSSION: This will be the first clinical trial to assess the best antiplatelet therapy to avoid in-stent thrombosis after MT in patients with TL. TRIAL REGISTRATION: The trial is registered as NCT05225961. February, 7th, 2022.

The Efficacy and Safety of Tirofiban Use in Endovascular Thrombectomy for Intravenous Thrombolysis Applicable Patients with Large Vessel Occlusion Stroke-a Post Hoc Analysis from the Direct-MT Trial.

PURPOSE: The purpose of the study was to evaluate the efficacy and safety of tirofiban use in endovascular thrombectomy for intravenous thrombolysis applicable patients of large vessel occlusion stroke with data from Direct-MT trial. MATERIALS AND METHODS: Direct-MT was the first randomized controlled trial to prove the non-inferiority of thrombectomy alone to bridging therapy (intravenous thrombolysis before thrombectomy) for large vessel occlusion stroke. Patients who underwent endovascular procedure were included and divided into thrombectomy-alone group and bridging therapy group. The effect of tirofiban use on 90 days MRS distribution, MRS 0-2 and mortality, successful reperfusion, the ASPECTS and outcome lesion volume of index stroke, re-occlusion of the treated vessel, futile recanalization and safety outcomes were further evaluated in both groups after adjustment for relevant confounding factors. The interaction between tirofiban and rt-PA was also assessed. RESULTS: Of 639 patients included in this analysis, 180 patients underwent thrombectomy with tirofiban use (28.2%). Patients with tirofiban use had lower percentage of bridging therapy (41.1% vs 54.3%, P = 0.003), higher proportion of large artery atherosclerosis (P < 0.001) and more emergent stenting (30.56% vs 6.97%, P < 0.001). After adjustment for confounding factors, the 90-day modified Rankin Scale distribution, successful final recanalization rate, outcome lesion volume of index stroke on CT and intracranial hemorrhage risk showed no difference after tirofiban use in thrombectomy-alone group and in bridging therapy group. No interaction effect between tirofiban and rt-PA was detected. CONCLUSION: Based on data from Direct-MT trial, tirofiban is a safe medication for intravenous thrombolysis applicable patients with large vessel occlusion stroke undergoing thrombectomy. LEVEL OF EVIDENCE: Level 3, cohort study of randomized trial.

Aspiration Thrombectomy Versus Stent-Retriever Thrombectomy for the First-Pass Therapy of Intracranial Atherosclerosis-Related Large Vessel Occlusion: A Post Hoc Analysis of The Endovascular Treatment With Versus Without Tirofiban for Patients with Large Vessel Occlusion Stroke Trial.

BACKGROUND: This study sought to scrutinize the clinical outcomes associated with first-pass mechanical thrombectomy strategies in the management of intracranial atherosclerosis (ICAS)-related large vessel occlusion (LVO). METHODS: Within this post-hoc analysis of the The Endovascular Treatment With vs Without Tirofiban for Patients with Large Vessel Occlusion Stroke (RESCUE BT) trial, we compared data pertaining to patients with ICAS-LVO situated in the anterior circulation who underwent initial therapeutic interventions utilizing either aspiration thrombectomy or stent-retriever thrombectomy. The analysis encompassed the assessment of intraprocedural recanalization, rescue procedures involving balloon angioplasty or stenting, 48-hour reocclusion rates, occurrences of cerebral hemorrhagic complications, and 90-day Modified Rankin Scale scores. RESULTS: Among the 948 patients encompassed in the RESCUE BT trial, a total of 230 patients with ICAS-LVO in the anterior circulation were enrolled in the study. Of these, 111 underwent aspiration thrombectomy as the first-pass therapy, while 119 patients underwent stent-retriever thrombectomy as the initial intervention. The difference in first pass recanalization rates between aspiration thrombectomy and stent-retriever thrombectomy was not statistically significant (17.1% vs. 14.3%, P = 0.555), and mechanical thrombectomy success rates (90.1% vs. 90.8%, P = 0.864), the use of balloon angioplasty or stenting for rescue therapy (54.6% vs. 45.9%, P = 0.189; 23.4% vs. 25.2%, P = 0.752), and favorable 90-day Modified Rankin Scale outcomes (53.2% vs. 40.3%, P = 0.051) showed no statistically significant differences. CONCLUSIONS: Both aspiration thrombectomy and stent-retriever thrombectomy can be considered as primary therapeutic options for patients presenting with ICAS-LVO in the anterior circulation.

Association of tirofiban treatment with outcomes following endovascular therapy in cardioembolic stroke: insights from the RESCUE BT randomized trial.

BACKGROUND AND PURPOSE: The efficacy and safety of tirofiban in endovascular therapy for cardioembolic ischemic stroke patients remain controversial. This study aimed to evaluate the role of intravenous tirofiban before endovascular therapy in cardioembolic stroke. METHODS: This post hoc analysis utilized data from the RESCUE BT (Endovascular Treatment With versus Without Tirofiban for Patients with Large Vessel Occlusion Stroke) trial, which was an investigator-initiated, randomized, double-blind, placebo-controlled trial. Participants were randomized to receive either tirofiban or a placebo in a 1:1 ratio before undergoing endovascular therapy. The study included patients aged 18 years or older, presenting with occlusion of the internal carotid artery or middle cerebral artery (MCA) M1/M2 within 24 h of the last known well time, and with a stroke etiology of cardioembolism. The primary efficacy outcome was global disability at 90 days, assessed using the modified Rankin Scale (mRS). The safety outcome included symptomatic intracranial hemorrhage (sICH) within 48 h and mortality within 90 days. RESULTS: A total of 406 cardioembolic stroke patients were included in this study, with 212 assigned to the tirofiban group and 194 assigned to the placebo group. Tirofiban treatment did not correlate with a favorable shift towards a lower 90-day mRS score (adjusted common odds ratio [OR], 0.91; 95% CI 0.64-1.3; p = 0.617). However, the tirofiban group had a significantly higher risk of symptomatic intracranial hemorrhage (sICH) within 48 h (adjusted OR, 3.26; 95% CI 1.4-7.57; p = 0.006) compared to the placebo group. The adjusted odds ratio (aOR) for mortality within 90 days was 1.48 (95% CI 0.88-2.52; p = 0.143). CONCLUSIONS: Tirofiban treatment was not associated with a lower level of disability and increased the incidence of sICH after endovascular therapy in cardioembolic stroke patients.

In ischemic stroke without large or medium vessel occlusion, tirofiban increased likelihood of an excellent outcome.

SOURCE CITATION: Zi W, Song J, Kong W, et al; RESCUE BT2 Investigators. Tirofiban for stroke without large or medium-sized vessel occlusion. N Engl J Med. 2023;388:2025-2036. 37256974.

Association of tirofiban with improvement of functional outcomes of direct thrombectomy for acute anterior circulation occlusion: a retrospective, nonrandomized, multicenter, real-world study.

OBJECTIVE: Although tirofiban and endovascular thrombectomy have been widely used in the treatment of acute ischemic stroke (AIS) patients, the effectiveness of their combined application remains a subject of debate. This study aimed to assess the efficacy and safety of tirofiban in direct thrombectomy for AIS with anterior circulation vessel occlusion. METHODS: A total of 204 patients undergoing direct thrombectomy between January 2020 and December 2021 for AIS with anterior circulation vessel occlusion from four hospitals were included in this study. Patients at high risk of reocclusion with severe atherosclerosis, those who achieved successful recanalization for ≥ 3 stent retriever passes, or those who underwent emergency stenting or balloon angioplasty for severe residual stenosis were treated with tirofiban. Following a low-dose intra-arterial bolus (0.25-1 mg) immediately after endovascular treatment, tirofiban was administered continuously through intravenous infusion (0.1 µg/kg/min) for 12-24 hours. The primary efficacy outcome was evaluated using the 90-day modified Rankin Scale score. The safety outcome was assessed using symptomatic intracerebral hemorrhage (sICH) and mortality rates. RESULTS: The tirofiban group and nontirofiban group each included 102 patients. The favorable outcome rate in the tirofiban group was significantly higher than that in the nontirofiban group (53.9% vs 35.3%, p = 0.007). However, the sICH and 90-day mortality rates were lower in the tirofiban group, despite a lack of statistical significance (sICH: 15.7% vs 16.7%, p = 0.849; 90-day mortality: 16.67% vs 24.51%, p = 0.166). Finally, it was found that older patients (> 72 years), male patients, patients with admission National Institutes of Health Stroke Scale scores > 14, patients with a time from onset to reperfusion > 327 minutes, and patients with a medical history of diabetes tend to benefit from tirofiban treatment. CONCLUSIONS: This study suggests that tirofiban combined with direct thrombectomy improves functional outcomes of AIS and reduces the 90-day mortality rate. Therefore, it could be considered as a suitable treatment option for AIS patients with anterior circulation vessel occlusion.

Systematic review and meta-analysis of the efficacy and safety of adjunctive use of tirofiban in patients treated with endovascular therapy for acute ischemic stroke at different embolic sites.

BACKGROUND: The use of tirofiban as an adjunct to endovascular therapy (EVT) for acute ischemic stroke has been controversial. We aimed to assess the differences in safety and efficacy of EVT adjuvant to tirofiban in patients with anterior circulation stroke (ACS) and posterior circulation stroke (PCS). METHODS: We systematically searched Pubmed, Embase, Cochrane Library, and Web of Science. Cohort studies and randomized controlled trials that compared treatment with tirofiban combined with EVT and EVT alone were included in our meta-analysis. The safety outcomes were symptomatic intracranial hemorrhage, and 3-month mortality. The efficacy outcomes were good functional outcome, excellent functional outcome, and successful recanalization (mTICI ≥ 2b). We performed subgroup analyses of anterior and posterior circulation strokes. RESULTS: We included 15 studies with 4608 patients. For safety outcomes, tirofiban significantly reduced 3-month mortality in the ACS subgroup (odd ratio [OR] = 0.80, 95% confidence interval [CI] = 0.65-0.98, P = .03) without increasing the rate of symptomatic intracranial hemorrhage (OR = 1.12, 95% CI = 0.88-1.44, P = .35). In the PCS subgroup, tirofiban significantly reduced 3-month mortality (OR = 0.63, 95% CI = 0.50-0.80, P = .0001) and symptomatic intracranial hemorrhage (OR = 0.60, 95% CI = 0.37-0.95, P = .03). For efficacy outcomes, in the ACS subgroup, tirofiban significantly improved good functional outcome (OR = 1.24, 95% CI = 1.06-1.45, P = .008) but did not improve recanalization (OR = 1.17, 95% CI = 0.93-1.47, P = .17) and excellent functional outcome (OR = 1.19, 95% CI = 0.97-1.46, P = .10). In the PCS subgroup, tirofiban significantly improved recanalization rate (OR = 1.94, 95% CI = 1.43-2.65, P < .0001) and did not improve good functional outcome (OR = 1.03, 95% CI = 0.81-1.30, P = .81) and excellent functional outcome (OR = 0.84, 95% CI = 0.58-1.20, P = .34). CONCLUSION: In acute ischemic stroke patients undergoing EVT, tirofiban improves good functional outcomes in ACS patients and increases recanalization rates in PCS patients on the 1 hand, reduces mortality, and does not increase the risk of symptomatic intracranial hemorrhage on the other. Tirofiban is safe and effective in both anterior circulation stroke and posterior circulation stroke patients undergoing EVT. More large multicentre randomized controlled studies are needed in the future.

Acute Vertebrobasilar Artery Occlusion with Underlying Atherosclerosis: Balloon Angioplasty Combined with Tirofiban as Initial Salvage Therapy.

OBJECTIVE: The optimal rescue endovascular treatment for patients with intracranial atherosclerotic stenosis in acute vertebrobasilar artery occlusion is not well established. We investigated the safety and efficacy of balloon angioplasty combined with tirofiban as the initial rescue strategy in these patients. METHODS: We retrospectively analyzed the records of 41 patients admitted between January 2014 and September 2022, with vertebrobasilar artery atherosclerotic occlusion. Balloon angioplasty in combination with tirofiban was used as the first-line salvage therapy after the failure of mechanical thrombectomy. The technical success rate, recanalization outcome, procedure-related complications, symptomatic intracranial hemorrhage, and functional outcome at 90 days were reviewed. RESULTS: Recanalization with a modified Thrombolysis in Cerebral Infarction grade of 2b-3 was achieved in 38 of the 41 patients (92.7%). Acute stents were deployed in 5 patients who did not achieve successful reperfusion after balloon angioplasty. Six patients (14.6%, 6/41) underwent stent angioplasty in the stable stage for severe residual stenosis detected on follow-up imaging. There was no procedure-related complication. Hemorrhagic transformation was detected on follow-up imaging in 11 patients (26.8%), while no symptomatic intracranial hemorrhage was recorded. Good functional outcome rate was 31.7% (13/41). CONCLUSIONS: Balloon angioplasty combined with intravenous tirofiban administration is a safe and effective salvage therapy in patients with acute atherosclerotic occlusion of the vertebrobasilar artery.

Clinical efficacy and the influence of fibrinogen, homocysteine and prognosis in acute ischemic stroke patients treated with tirofiban plus TERVO stent thrombectomy.

To evaluate the clinical efficacy and the influence of fibrinogen, homocysteine and prognosis in acute ischemic stroke (AIS) treated with tirofiban plus TERVO stent thrombectomy. A retrospective study was conducted among 82 patients with AIS admitted to the Department of Neurology in Hengshui People's Hospital from December 2018 to December 2020 and they were evenly divided into control group and study group according to different methods. The control group received TERVO stent thrombectomy; the study group received tirofiban plus. The clinical efficacy, modified thrombolysis in cerebral infarction (mTICI) grade, serum levels of fibrinogen and homocysteine, National Institute of Health stroke scale (NIHSS), and activity of daily living (ADL) scores were compared. Significant higher clinical efficacy was observed in the study group vs. control group (all p<0.05). The study group witnessed lower percentage of 0~1 grade of mTICI blood flow in relative to the control group (all p<0.05). After treatment, significant reduction was observed in FIB and HCY in both groups, but the treatment in the study group resulted in a greater reduction (all p<0.05). After treatment, both groups reported a significant increase in NIHSS score and ADL score, with more increase in the study group (all p<0.05). The safety profiles were similar in the two groups with respect to the adverse reactions (p>0.05). Tirofiban plus TERVO stent thrombectomy could improve vascular recanalization rate, reduce fibrinogen and homocysteine levels and improve short-term prognosis in AIS patients.

Tirofiban in the treatment of cancer-associated ischemic stroke.

OBJECTIVE: It is still unknown whether early tirofiban treatment improves prognosis in patients with cancer-related ischemic stroke without intravenous thrombolytic therapy. The purpose of this study was to assess the safety and efficacy of tirofiban in patients with cancer-associated ischemic stroke. PATIENTS AND METHODS: A retrospective analysis was performed on 75 patients with cancer and mild to moderate ischemic stroke, 34 of whom received tirofiban treatment and 41 aspirin treatment. The aspirin group received aspirin 100 mg QD, while the tirofiban group received continuous intravenous administration of tirofiban at a dosage of 0.1 µg/kg/min for 48 hours before switching to oral aspirin. RESULTS: The 24-hour and 7-day National Institute of Health Stroke Scale (NIHSS) scores for the tirofiban group were lower than those for the aspirin group (p=0.017 and p=0.035, respectively). The proportion of intracerebral hemorrhage occurring within 7 days did not differ significantly between the two groups (p>0.05), and neither did the 90-day Modified Rankin Scale (mRS) scores nor the incidence of ischemic stroke. CONCLUSIONS: Early administration of tirofiban in the treatment of mild to moderate ischemic stroke is safe, which can reduce 24-hour and 7-day NIHSS scores and has potential value.

Tirofiban for Stroke without Large or Medium-Sized Vessel Occlusion.

BACKGROUND: The effects of the glycoprotein IIb/IIIa receptor inhibitor tirofiban in patients with acute ischemic stroke but who have no evidence of complete occlusion of large or medium-sized vessels have not been extensively studied. METHODS: In a multicenter trial in China, we enrolled patients with ischemic stroke without occlusion of large or medium-sized vessels and with a National Institutes of Health Stroke Scale score of 5 or more and at least one moderately to severely weak limb. Eligible patients had any of four clinical presentations: ineligible for thrombolysis or thrombectomy and within 24 hours after the patient was last known to be well; progression of stroke symptoms 24 to 96 hours after onset; early neurologic deterioration after thrombolysis; or thrombolysis with no improvement at 4 to 24 hours. Patients were assigned to receive intravenous tirofiban (plus oral placebo) or oral aspirin (100 mg per day, plus intravenous placebo) for 2 days; all patients then received oral aspirin until day 90. The primary efficacy end point was an excellent outcome, defined as a score of 0 or 1 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days. Secondary end points included functional independence at 90 days and a quality-of-life score. The primary safety end points were death and symptomatic intracranial hemorrhage. RESULTS: A total of 606 patients were assigned to the tirofiban group and 571 to the aspirin group. Most patients had small infarctions that were presumed to be atherosclerotic. The percentage of patients with a score of 0 or 1 on the modified Rankin scale at 90 days was 29.1% with tirofiban and 22.2% with aspirin (adjusted risk ratio, 1.26; 95% confidence interval, 1.04 to 1.53, P = 0.02). Results for secondary end points were generally not consistent with the results of the primary analysis. Mortality was similar in the two groups. The incidence of symptomatic intracranial hemorrhage was 1.0% in the tirofiban group and 0% in the aspirin group. CONCLUSIONS: In this trial involving heterogeneous groups of patients with stroke of recent onset or progression of stroke symptoms and nonoccluded large and medium-sized cerebral vessels, intravenous tirofiban was associated with a greater likelihood of an excellent outcome than low-dose aspirin. Incidences of intracranial hemorrhages were low but slightly higher with tirofiban. (Funded by the National Natural Science Foundation of China; RESCUE BT2 Chinese Clinical Trial Registry number, ChiCTR2000029502.).

Safety and efficacy of tirofiban in acute ischemic stroke due to tandem lesions undergoing mechanical thrombectomy: A multicenter randomized clinical trial (ATILA) protocol.

Background: In-stent thrombosis after mechanical thrombectomy (MT) worsen outcomes in acute ischemic stroke (AIS) due to tandem lesions (TL). Although an optimal antiplatelet therapy is needed, the best approach to avoid in-stent thrombosis is yet to be elucidated. Hypothesis: Low-dose intravenous tirofiban is superior to intravenous aspirin in avoiding in-stent thrombosis in patients undergoing MT plus carotid stenting in the setting of AIS due to TL. Methods: The ATILA-trial is a multicenter, prospective, phase IV, randomized, controlled (aspirin group as control), assessor-blinded clinical trial. Patients fulfilling inclusion criteria (AIS due to TL, ASPECTS ⩾ 6, pre-stroke modified Rankin Scale ⩽2 and onset <24 h) will be randomized (1:1) at MT onset to experimental (intravenous tirofiban) or control group (intravenous aspirin). Intravenous aspirin will be administered at a 500 mg single dose and tirofiban at a 500 µg bolus followed by a 200 µg/h infusion during first 22 h. All patients will be followed up to 3 months. Sample size estimated is 240 patients. Outcomes: The primary efficacy outcome is the proportion of patients with carotid in-stent thrombosis within the first 24 h after MT. The primary safety outcome is the rate of symptomatic intracranial hemorrhage. Secondary outcomes include functional independence defined as modified Rankin Scale 0-2, proportion of patients undergoing rescue therapy due to in-stent aggregation during MT and carotid reocclusion at 30 days. Discussion: ATILA-trial will be the first clinical trial regarding the best antiplatelet therapy to avoid in-stent thrombosis after MT in patients with TL. Trial registration: NCT0522596.

Meta-analysis of the efficacy and safety of tirofiban in patients with acute ischaemic stroke undergoing mechanical thrombectomy.

INTRODUCTION: Mechanical thrombectomy is now widely used in acute ischaemic stroke, but its adjunctive antiplatelet aggregation regimen is controversial. This study aimed to investigate the safety and efficacy of tirofiban in patients with acute ischaemic stroke (AIS) who underwent mechanical thrombectomy. METHODS: We systematically searched Pubmed, Embase, Cochrane Library, and Web of science. Randomized controlled studies and cohort studies comparing the tirofiban group and non-tirofiban group (control group) in patients with AIS who underwent mechanical thrombectomy. The primary safety outcomes were symptomatic intracranial hemorrhage (sICH), 3-month mortality, and re-occlusion rate. The primary efficacy outcomes were good functional outcome (mRS 0-2), excellent functional outcome (mRS 0-1), and successful recanalization (mTICI≥2b). RESULTS: We included 22 studies with a total of 6062 patients. For safety outcomes, the tirofiban group had a non-significantly higher rate of sICH (OR = 0.90, 95 % CI = 0.73-1.10, P = 0.29) and a significantly lower rate of re-occlusion (OR = 0.40, 95 % CI = 0.19-0.82, P = 0.01) and 3-month mortality (OR = 0.71, 95 % CI = 0.61-0.82, P < 0.00001) compared to the control group. In terms of efficacy outcomes, significant improvement in good functional outcomes (mRS 0-2) (OR = 1.24, 95 % CI = 1.11-1.39, P = 0.0002) and recanalization rate (OR = 1.38, 95% CI = 1.17-1.62, P = 0.0001) compared to tirofiban, but not significant improvement in excellent functional outcomes(OR = 1.14, 95 % CI = 0.93-1.39, P = 0.21). In addition, compared with cardiogenic stroke, the large atherosclerotic stroke had a higher rate of good functional outcome (OR = 1.58, 95 % CI = 1.18-2.11, P = 0.002) and a lower rate of 3-month mortality (OR = 0.58, 95 % CI = 0.39-0.85, P = 0.005). Subgroup analysis by route of administration showed a significant improvement in good functional outcome in the intravenous group (OR = 1.27, 95 % CI = 1.08-1.50, P = 0.004), while no significant difference was found between the arterial and arteriovenous groups. CONCLUSION: Treatment with tirofiban in patients with AIS with mechanical thrombectomy is effective in improving functional prognosis, arterial recanalization rates, and reducing 3-month mortality and re-occlusion rates, particularly in patients with large atherosclerotic stroke, without increasing the rate of symptomatic intracranial hemorrhage. Intravenous administration of tirofiban significantly improves the clinical prognosis compared to arterial administration. Tirofiban is effective and safe in patients with AIS.

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.