Propensity score-adjusted analysis on early tirofiban administration to prevent thromboembolic complications during stand-alone coil embolization of ruptured aneurysms.

The glycoprotein IIb/IIIa antagonist tirofiban has been shown to prevent thromboembolic events during endovascular procedures, but the benefits and risks of its prophylactic early intraprocedural administration for stand-alone coil embolization of acutely ruptured aneurysms are still unclear. We conducted a retrospective single-center analysis of patients treated for aneurysmal subarachnoid hemorrhage with stand-alone coil embolization. Two study cohorts were compared according to the primary prophylactic antithrombotic medication during the procedure: patients receiving only intravenous heparin (HEP) versus patients receiving tirofiban in addition to heparin prior to final aneurysm obliteration (HEP + TF). Outcome endpoints were the incidence of angiographically visible thrombus formation or distal embolization, and the incidence of periprocedural intracranial hemorrhage (ICH). Of 204 cases, 159 were prophylactically treated with HEP and 45 with HEP + TF. Intraprocedural thromboembolic events were less frequent with HEP + TF before and after propensity score matching (PSM) (2.5% vs. 19.7%, p = 0.017). The incidence of ICH and symptomatic ICH did not differ between HEP + TF and HEP before and after PSM (20.5% vs. 30.7%, p = 0.29; and 5.1% vs. 4%, p = 0.88). Early intraprocedural tirofiban administration may be effective in preventing thromboembolic complications during stand-alone coil embolization of acutely ruptured aneurysms without increasing the risk of ICH.

Tirofiban vs. aspirin in patients with acute ischemic stroke: A meta-analysis of randomized clinical trials.

BACKGROUND AND OBJECTIVES: Antiplatelet therapy is recommended as the standard treatment for patients with acute ischemic stroke (AIS) who, for several reasons, did not receive thrombolysis or thrombectomy. However, whether tirofiban or aspirin provides greater benefits for these patients remains unclear. Therefore, we aimed to perform a meta-analysis comparing the functional outcomes and hemorrhagic risks associated with tirofiban and aspirin in the management of AIS. METHODS: We searched PubMed, EMBASE, Web of Science, and Cochrane Library for studies comparing tirofiban to aspirin in patients with AIS who did not receive thrombolysis or thrombectomy until September 2024. Outcomes were modified Rankin Scale (mRS) and mortality at 90 days, symptomatic intracranial hemorrhage, and any bleeding events. Statistical analysis was performed using the R Studio (version 2024.04.1+748). RESULTS: We included 3 randomized controlled trials with a total of 1959 patients, of whom 996 (50.8 %) were in the tirofiban group. Excellent (mRS 0-1) functional outcome (RR 1.25, 95 % CI: 1.05-1.49; I2 = 70 %) and favorable (mRS 0-2) functional outcome at 90 days (RR 1.09, 95 % CI: 1.01-1.16; I2 = 35 %) were significantly higher in tirofiban compared to aspirin. Furthermore, tirofiban showed no difference in mortality (RR 0.77, 95 % CI: 0.24-2.53; I2 = 56 %), or symptomatic intracranial hemorrhage (RR 3.42, 95 % CI: 0.27-43.30; I2 = 38 %). However, any bleeding event (RR 1.75, 95 % CI: 1.25-2.45; I2 = 0 %) was more common in the tirofiban group. Lastly, the meta-regression analysis showed that the outcomes were not influenced by the initial NIHSS of the included studies (p > 0.05). CONCLUSION: Tirofiban is associated with better functional outcomes at 90 days, with no difference in mortality. Additionally, despite being associated with higher bleeding events, there is no difference in symptomatic intracranial hemorrhage. Therefore, our results suggest that tirofiban is a promising alternative to aspirin.

Effect of Intravenous Tirofiban Versus Placebo on First-Pass Successful Reperfusion in Endovascular Stroke Thrombectomy: Insights From the RESCUE BT Randomized Clinical Trial.

BACKGROUND: First-pass successful reperfusion (FPSR), defined as a successful/complete reperfusion achieved after a single thrombectomy pass, is predictive of favorable outcome in patients with acute ischemic stroke with large-vessel occlusion. It is unknown whether intravenous tirofiban is effective in increasing the rate of FPSR in acute anterior large-vessel occlusion stroke. METHODS AND RESULTS: Patients who had acute large-vessel occlusion stroke presenting within 24 hours and underwent endovascular thrombectomy were analyzed from the RESCUE BT (Intravenous Tirofiban for Patients With Large Vessel Occlusion Stroke) clinical trial, of which the main analysis was neutral. The RESCUE BT trial randomized patients to receive either intravenous tirofiban or placebo before endovascular thrombectomy. The primary end point was FPSR, defined as successful reperfusion (extended thrombolysis in cerebral infarction scale 2b50, 2c, or 3) at first thrombectomy attempt. A modified Poisson regression analysis assessed the association between intravenous tirofiban treatment and FPSR. Of 948 enrolled patients, 463 patients were randomized to the tirofiban group and 485 to the placebo group. The mean age was 67 years, and 41.0% of the patients were women. FPSR was achieved more often in the tirofiban group (30.5% versus 23.5%; adjusted risk ratio, 1.24 [95% CI, 1.01-1.51]; P=0.04). FPSR was associated with a favorable shift to lower modified Rankin Scale disability levels at 90 days (common odds ratio, 1.42 [95% CI, 1.08-1.86]; P=0.01). CONCLUSIONS: In this post hoc analysis of the RESCUE BT trial, treatment with intravenous tirofiban before endovascular thrombectomy was associated with increased FPSR in patients with acute ischemic stroke due to large-vessel occlusion in the anterior circulation. FPSR was associated with reduced 90-day levels of disability. REGISTRATION: URL: http://chictr.org; Unique Identifier: ChiCTR-INR-17014167.

Clinical efficacy of tirofiban in the endovascular therapy of patients with acute ischaemic stroke due to intracranial atherosclerotic disease: A meta-analysis.

OBJECT: The treatment results of combination of arterial injection of tirofiban with endovascular therapy (EVT) for acute large vessel occlusion (LVO) stroke due to intracranial atherosclerotic disease (ICAD) were inconsistent. This meta-analysis aims to assess the safety and efficacy of ICAD-LVO treatment by intra-arterial injection of tirofiban combined with EVT. METHODS: Relevant studies were identified through a systematic literature search in Pubmed, EMBASE, Web of Science and Cochrane Library databases, covering articles published from January 2010 to July 2024. The efficacy outcomes assessed in the meta-analysis included favorable functional outcome and recanalization rates. Safety outcomes included mortality and symptomatic intracranial haemorrhage (sICH). RESULTS: The meta-analysis consisted of data from 11 studies, which included 1 randomised controlled trial (RCT), 5 prospective cohort studies, and 5 retrospective cohort studies, encompassing a total of 2869 patients. The findings showed that tirofiban+EVT for ICAD-LVO was associated with significant improvements in favorable functional outcomes (RR, 1.12; 95 %CI, 1.04-1.21; P=0.005) and reductions in mortality rates (RR, 0.72; 95 %CI, 0.62-0.83; P<0.0001), despite no significant differences in the incidence of sICH (RR, 0.75; 95 % CI, 0.55-1.02; P=0.07) and recanalization rates (RR, 1.02; 95 % CI, 0.99-1.05; P=0.15). Subgroup analysis showed that the application of tirofiban significantly increased favorable functional outcomes in patients with anterior circulation stroke (RR, 1.23; 95 % CI, 1.06-1.42; P=0.005), but there was no significant difference in posterior circulation stroke (RR, 1.08; 95 % CI, 0.83-1.41; P=0.55). In addition, the use of tirofiban in patients with posterior circulation stroke might reduce the incidence of sICH (RR, 0.50; 95 % CI, 0.26-0.96; P=0.04). CONCLUSION: Tirofiban combined with EVT may be an effective treatment strategy for the treatment of ICAD-LVO, but only for patients with anterior circulation and remains unclear for patients with posterior circulation.

"Y appearance" infarction: caused by essential thrombocythemia.

Essential thrombocythemia (ET) is a myeloproliferative malignancy caused by the excessive proliferation of megakaryocytes in the bone marrow, resulting in the overproduction of peripheral platelets. ET can lead to thrombotic events, such as ischemic stroke (IS), though it is a rare cause of IS. Bilateral medial medullary infarction (BMMI), also known as "Y appearance" infarction due to its distinctive imaging morphology, is a rare clinical subtype of IS which typically has a poor prognosis and a high mortality rate. Herein, we report the case of a 43-year-old male with a history of ET. The patient's platelet count was poorly controlled, and he did not receive regular treatment. After developing symptoms such as dizziness, dysphagia, choking on water, slurred speech, blurred vision, and bilateral limb numbness. Head magnetic resonance imaging revealed a "Y appearance" infarction in the bilateral medial medulla. After admission, the patient was administered intravenous antiplatelet therapy with tirofiban. However, when he was switched to oral aspirin after three days, he experienced decreased muscle strength and worsening symptoms. Therefore, tirofiban was continued for 14 days. Upon discharge, the patient experienced residual limb numbness. His National Institutes of Health Stroke Scale score was 1, Modified Rankin Scale score was 0, and platelet count had decreased to the normal range. During the 9-month follow-up period after discharge, the patient still had only mild limb numbness. Our report presents a special case of "Y appearance" infarction due to ET. Owing to fluctuations in the patient's condition, he received long-term high-dose tirofiban, which ultimately led to a significant improvement in his symptoms.

Effectiveness of different tirofiban administration times in patients with no-reflow myocardial infarction during percutaneous coronary intervention.

Objective: To compare the effectiveness of different tirofiban administration time windows in patients with no-reflow myocardial infarction (MI) during percutaneous coronary intervention (PCI). Methods: This single centre retrospective observational study included patients with no-reflow MI, undergoing PCI at the Hanyang Hospital affiliated to Wuhan University of Science and Technology from March 2020 to May 2023. All patients were administered tirofiban. Patients who received tirofiban with postinterventional thrombolysis in myocardial infarction (TIMI) flow ≥ 1 were grouped as Group-I, and patients who were directly given tirofiban through the guiding catheter without forward blood flow were grouped as Group-II. TIMI blood flow classification, levels of cardiac troponin T (cTnT) and creatine kinase isoenzyme MB (CK-MB), incidence of complications and major adverse cardiovascular events (MACE) in the two groups before and after the treatment were statistically analyzed. Results: A total of 156 patients were included in this study, including 79 patients in Group-I and 77 patients in Group-II. There was no significant difference in the baseline data between the two groups (P>0.05). After treatment, TIMI blood flow classification of the two groups improved and was significantly better in Group-I compared to Group-II (P<0.05). After treatment, levels of Serum cTnT and CK-MB in the two groups decreased, and were significantly lower in Group-I than in Group-II (P<0.05). There was no significant difference in the incidence of complications between Group-I (3.80%) and Group-II (6.49%) (P>0.05). The incidence of MACE in Group-I (3.80%) was lower than that in Group-II (12.99%) (P<0.05). Conclusions: Compared with the direct application of tirofiban, tirofiban given when TIMI Grade≥ 1 for patients with no-reflow MI during PCI can more effectively regulate the blood flow status of target vessels, reduce myocardial injury, and reduce the risk of MACE.

Effects of different doses of tirofiban combined with dual antiplatelet drugs on platelet indices, vascular endothelial function, and major adverse cardiovascular events in patients with acute ST-segment elevated myocardial infarction undergoing percutaneous coronary intervention.

This trial targeted to analyze the effects of different doses of tirofiban combined with dual antiplatelet drugs on platelet indices, vascular endothelial function, and major adverse cardiovascular events (MACE) in patients with acute ST-segment elevated myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). A total of 180 patients with STEMI who underwent PCI were divided into Group A, Group B, and Group C (60 cases per group). Group A was given conventional medication, and Groups B and C were given a standard dose (10 µg/kg) and a high dose (20 µg/kg) of tirofiban on the basis of Group A, respectively. Thrombolysis in myocardial infarction (TIMI) myocardial perfusion grade and TIMI blood flow grade were compared. Myocardial enzymes, platelet indices, vascular endothelial function, inflammatory factors, and cardiac function indices were detected. In-hospital bleeding events and follow-up MACE were recorded. After PCI, Group C had a higher number of TIMI myocardial perfusion grade III and TIMI blood flow grade III versus Group A. Group C achieved the greatest changes in myocardial enzymes, platelet indices, vascular endothelial function-related factors, inflammatory factors, and cardiac function indices, followed by Group B and Group A. The incidence of bleeding events was higher in Group C than in Group A, and that of MACE in Group C was lower than in Group A. The addition of high-dose tirofiban to PCI and dual antiplatelet drugs for STEMI patients can improve myocardial blood perfusion, cardiac function, and vascular endothelial function, inhibit platelet activation and aggregation, and reduce the occurrence of MACE.

What is the context?Acute myocardial infarction is a branch of acute coronary syndromes, which can be categorized into ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction. Percutaneous coronary intervention is a non-surgical, invasive treatment used to improve blood flow to ischemic tissues and relieve coronary artery stenosis or occlusion. Despite the fact that percutaneous coronary intervention allows for timely mechanical reperfusion, patients with myocardial infarction have to face an increased risk of adverse cardiovascular events.What is the new?The addition of high-dose tirofiban to percutaneous coronary intervention and dual antiplatelet drugs for ST-segment elevation myocardial infarction patients can improve myocardial blood perfusion, cardiac function, and vascular endothelial function, inhibit platelet activation and aggregation, and reduce the occurrence of major adverse cardiovascular events.What is the impact?These findings favor the future application of tirofiban combination therapies and can improve patients' conditions alone.

Leukoaraiosis in patients with tirofiban before endovascular thrombectomy: A post hoc analysis of a multicentre randomized clinical trial.

BACKGROUND AND PURPOSE: To evaluate the effectiveness and safety of intravenous tirofiban before endovascular thrombectomy in subgroups of acute ischemic stroke patients with different degrees of leukoaraiosis (LA). METHODS: Patients of the RESCUE BT trial whose LA grade could be assessed were included. Eligible patients were dichotomized into two strata according to the van Swieten scale (VSS) score, absent-to-moderate LA (VSS score <3) and severe LA (VSS score ≥3). Furthermore, patients were divided into tirofiban and placebo groups in each stratum. The primary outcome was the 90-day modified Rankin Scale (mRS) score. Safety outcome was radiological intracranial hemorrhage within 48 h. RESULTS: 861 patients were included, 439 patients with absent-to-moderate LA and 422 patients with severe LA. There were no significant differences in 90-day mRS score between the tirofiban and placebo groups in either stratum (absent-to-moderate LA: adjusted OR 0.92 (95%CI, 0.66-1.28), P = 0.62; severe LA: adjusted OR 0.99 (95% CI, 0.69-1.42), P = 0.96). In the severe LA stratum, the occurrence of radiologic intracranial hemorrhage was greater in the tirofiban group compared to the placebo group. (35.7% vs 26.4%; adjusted OR, 1.72 (95% CI, 1.12-2.66); P = 0.014). However, no difference was observed in the absent-to-moderate LA stratum (33.2% vs 29.3%; adjusted OR, 1.15 (95% CI, 0.76-1.75); P = 0.51). CONCLUSION: There was no significant difference in disability severity at 90 days when treating AIS patients using intravenous tirofiban before endovascular therapy, in either absent-to-moderate or severe LA strata. It should be noted that intravenous tirofiban before endovascular therapy increases the incidence of radiologic intracranial hemorrhage in patients with severe LA.

Preoperative and intraoperative tirofiban during endovascular thrombectomy in large vessel occlusion stroke due to large artery atherosclerosis.

BACKGROUND AND PURPOSE: The aim of this study is to investigate the efficacy and safety of preoperative versus intraoperative tirofiban in patients with large vessel occlusion (LVO) due to large artery atherosclerosis (LAA). METHODS: This is a retrospective multicenter cohort study based on the RESCUE-RE (Registration Study for Critical Care of Acute Ischemic Stroke After Recanalization) trial enrolling patients with anterior circulation LVO classified as LAA within 24 h of onset. Patients were divided into three groups: preoperative tirofiban (PT), intraoperative tirofiban (IT), and no tirofiban (NT). Propensity score matching (PSM) was used to balance baseline characteristics. The efficacy outcomes included 90-day functional independence (modified Rankin Scale score = 0-2) and early partial recanalization (EPR; defined as a modified Thrombolysis in Cerebral Infarction score = 1-2a). The safety outcomes included symptomatic intracranial hemorrhage (sICH). RESULTS: A total of 104 matched triplets were obtained through PSM. Compared with NT, PT increased 90-day functional independence (60.8% vs. 42.3%, p = 0.008) and EPR (42.7% vs. 18.3%, p < 0.001) rate, with a tendency to increase the asymptomatic intracranial hemorrhage (aICH) proportion (28.8% vs. 18.3%, p = 0.072). Compared with IT, PT had a higher 90-day functional independence (60.8% vs. 45.2%, p = 0.025) and EPR (42.7% vs. 20.2%, p = 0.001) rate, with no significant difference in sICH (14.4% vs. 7.7%, p = 0.122) and aICH (28.8% vs. 21.2%, p = 0.200). Compared with NT, IT had a lower 90-day mortality rate (9.6% vs. 24.0%, p = 0.005). CONCLUSIONS: Tirofiban shows good adjuvant therapy potential in acute ischemic stroke-LVO due to LAA patients. PT is associated with higher rates of EPR and better therapeutic efficacy. In addition, EPR may be a potential way to improve prognosis.

Intracoronary Versus Intravenous Low-Dose Tirofiban in Patients With ST-Elevation Myocardial Infarction: A Meta-Analysis of Randomised Controlled Trials.

BACKGROUND: This meta-analysis aimed to evaluate the effects of intracoronary (IC) low-dose tirofiban versus intravenous (IV) administration on clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: All published randomised controlled trials (RCTs) comparing the effects of IC low-dose tirofiban (a bolus of ≤10 ug/kg) versus IV administration in patients with STEMI were identified by searching PubMed, EMBASE, Cochrane Library, and ISI Web of Science from inception to June 2023, with no language restriction. The risk ratio (RR) with 95% confidence intervals (CI) and the weighted mean difference (WMD) with 95% CI were calculated. RESULTS: Eleven RCTs involving 1,802 patients were included. Compared with the IV group, IC low-dose tirofiban was associated with improved major adverse cardiac events rate (RR 0.595, 95% CI 0.442-0.802; p=0.001), left ventricular ejection fraction (WMD 1.982, 95% CI 0.565-3.398; p=0.006), thrombolysis in myocardial infarction (TIMI) flow grade (RR 1.065, 95% CI 1.004-1.131; p=0.037), and TIMI myocardial perfusion grade (RR 1.194, 95% CI 1.001-1.425; p=0.049). The two groups had no significant difference in bleeding events (RR 0.952, 95% CI 0.709-1.279; p=0.745). CONCLUSIONS: Intracoronary low-dose tirofiban administration may be a safe and effective alternative to IV administration in STEMI patients.

Safety and efficacy of tirofiban in preventing neurological deterioration in acute ischemic stroke (TREND): Protocol for an investigator-initiated, multicenter, prospective, randomized, open-label, masked endpoint trial.

INTRODUCTION: Antithrombotic therapy prevents adverse ischemic events following acute ischemic stroke (AIS). Intravenous tirofiban provides desirable antiplatelet effects, especially in patients who are vulnerable to neurological deterioration (ND). AIM: The aim of the study was to test the hypothesis that intravenous administration of tirofiban, initiated within 24 h of ictus and continued for consecutive 72 h, would be more effective than aspirin in reducing the risk of ND within 72 h of enrollment among patients with potentially atherothrombotic ischemic stroke. METHODS: The Safety and Efficacy of Tirofiban in Preventing Neurological Deterioration in Acute Ischemic Stroke (TREND) trial is an investigator-initiated, multicenter, prospective, randomized, open-label, masked endpoint study. Its eligibility criteria included AIS secondary to potential atherosclerosis, a National Institutes of Health Stroke Scale (NIHSS) score ranging from 4 to 20 points, ineligibility for recanalization therapy, and administration within 24 h postsymptom onset. Randomization was performed at a 1:1 ratio to allocate 420 patients into two groups to receive an intravenous tirofiban bridge to oral antiplatelet drugs or direct oral antiplatelet drugs. OUTCOMES: The primary outcome is the proportion of patients with a ≥4-point increase in NIHSS score within 72 h of intervention compared to the score at enrollment. The key secondary outcomes include changes in NIHSS score, modified Rankin scale (mRS) score at 90 days, and dichotomized mRS scores (0-2 vs. 3-6 and 0-1 vs. 2-6) at 90 days. The safety variables are symptomatic intracerebral hemorrhage, any intracerebral hemorrhage, and systemic hemorrhage within 72 h after randomization and 90-day mortality. CONCLUSIONS: The TREND trial may identify the suitability of intravenous tirofiban as a routine clinical strategy to prevent ND in patients with AIS within 24 h of the onset of symptoms. TRIAL REGISTRATION: http://www.clinicaltrials.gov (identifier: NCT04491695).

Safety and effectiveness of LEO stents for dual stent-assisted embolization combined with IA and IV intra-procedural infusion of tirofiban in the treatment of wide-necked intracranial bifurcation aneurysms.

Objective: To evaluate the safety and efficacy of employing LEO stents in dual stent-assisted embolization (DSAE) for wide-necked intracranial bifurcation aneurysms, and to assess the effectiveness of combined IA and IV intra-procedural infusion of tirofiban in mitigating perioperative complications. Methods: Clinical data and follow-up images from 562 patients with wide-necked intracranial bifurcation aneurysms treated at First Affiliated Hospital of Army Medical University from 2018-2022 were collected. Among them, 65 received DSAE with LEO stents. The study observed treatment success rates, procedure-related complications, perioperative thromboembolic events (TEs) and hemorrhagic events (HEs), immediate postoperative modified Raymond-Roy classification (mRR), and follow-up imaging. Glasgow Outcome Scale (GOS) at discharge and clinical follow-ups were recorded. Results: The study enrolled 65 patients (mean age: 56.77 ± 10.07) with wide-necked intracranial bifurcation aneurysms. Among them, 58 had unruptured aneurysms, 7 ruptured (Hunt-Hess II-III). All aneurysms were successfully embolized without significant stent or bleeding complications. Only one case had intraoprative thrombosis; two postoperative ischemic incidents occurred within three days, no severe bleeding events. Immediate imaging showed modified Raymond-Roy classification: mRRC I (92.3%), mRRC II (4.6%), mRRC III b (3.1%). A total of 43 patients were followed up postoperatively with DSA. Among them, 41 patients exhibited mRRC I, while 2 patients exhibited mRRC II. No aneurysm was recanalized. Discharge GOS: GOS 5-60, GOS 4-1, GOS 3-4. One patient, GOS 1, died from lung cancer; others improved. Conclusion: The utilization of LEO stents for dual stent-assisted embolization of wide-necked intracranial bifurcation aneurysms demonstrated remarkable success and safety, yielding favorable postoperative outcomes and no instances of aneurysm recurrence. The concomitant administration of perioperative antiplatelet medications alongside IA and IV intra-procedural infusion of tirofiban effectively attenuated thromboembolic events (TEs) without concomitant elevations in bleeding risks.

Tirofiban mediates neuroprotective effects in acute ischemic stroke by reducing inflammatory response.

Growing evidence suggests that neuroinflammation is a critical driver of the development, worsening, and cell death observed in acute ischemic stroke (AIS). While prior research has demonstrated that tirofiban enhances functional recovery in AIS patients by suppressing platelet aggregation, its impact and underlying mechanisms in AIS-related neuroinflammation remain elusive. The current study established an AIS mouse model employing photochemical techniques and assessed neurological function and brain infarct size using the modified neurological severity scale (mNSS) and 2,3,5-Triphenyltetrazolium chloride (TTC) staining, respectively. Tirofiban significantly reduced the volume of cerebral infarction in AIS mice, accompanied by an enhancement in their neurological functions. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays along with experiments assessing oxidative stress showed that tirofiban mitigated oxidative damage and apoptosis in the ischemic penumbra post-AIS. Additionally, DNA microarray analysis revealed alterations in gene expression patterns in the ischemic penumbra after tirofiban treatment. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that most gene-level downregulated signaling pathways were closely related to the inflammatory response. Moreover, the protein microarray analysis revealed that tirofiban diminished the expression levels of inflammatory cytokines, such as interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha, in the ischemic penumbra. Additionally, immunofluorescence staining showed that tirofiban regulated inflammatory responses by altering the state and phenotype of microglia. In conclusion, this study suggests that tirofiban reduces inflammatory response by regulating microglial state and phenotype and lowering the levels of inflammatory factors, providing neuroprotection in acute ischemic stroke.

Safety and efficacy of tirofiban combined with intravenous thrombolysis and endovascular treatment in acute large vessel occlusion stroke.

OBJECTIVE: This study assesses the safety and efficacy of tirofiban for patients with large vessel occlusion stroke after intravenous thrombolysis. METHODS: This study data was from SUSTAIN, DEVT, and RESCUE BT trials. According to whether the use of tirofiban who underwent endovascular treatment and preceding intravenous thrombolysis was divided into the tirofiban group and the no-tirofiban group. The safety outcomes were symptomatic intracranial hemorrhage, any intracranial hemorrhage within 48 h, and 3-month mortality. The efficacy outcome was defined as a score of 0-2 on the modified Rankin Scale scores at 3 months. RESULTS: A total of 372 patients with intravenous thrombolysis were included in these SUSTAIN, DEVT, and RESCUE BT trials. Adjusted multivariate analysis showed that tirofiban with intravenous thrombolysis was not associated with symptomatic intracranial hemorrhage (aOR, 0.87; 95 % CI, 0.49-1.57; P=0.65), any intracranial hemorrhage within 48 h (aOR, 1.00; 95 % CI, 0.60-1.66; P=1.00), 3-month mortality (aOR, 1.10; 95 % CI, 0.56-2.19; P=0.78) and 3-month modified Rankin Scale scores 0-2 (aOR, 0.72; 95 % CI, 0.42-1.25; P=0.25) in patients with acute large vessel occlusion. In the subgroup analysis, we found that tirofiban was not recommended for females (aOR, 0.34; 95 % CI, 0.12-0.93), baseline Alberta Stroke Program Early CT Score≤9 (aOR, 0.37; 95 % CI, 0.18-0.76), and cardiogenic embolism (aOR, 0.36; 95 % CI, 0.14-0.97). CONCLUSION: Tirofiban combined with intravenous thrombolysis in patients with acute large vessel occlusion may be safe. Further studies need to confirm the effectiveness of tirofiban after intravenous thrombolysis in different stroke etiology.

Predictors of outcome in large vessel occlusion stroke patients with intravenous tirofiban treatment: a post hoc analysis of the RESCUE BT clinical trial.

OBJECTIVE: The aim of this study was to investigate the factors influencing good outcomes in patients receiving only intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke. METHODS: Post hoc exploratory analysis using the RESCUE BT trial identified consecutive patients who received intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke in 55 comprehensive stroke centers from October 2018 to January 2022 in China. RESULTS: A total of 521 patients received intravenous tirofiban, 253 of whom achieved a good 90-day outcome (modified Rankin Scale [mRS] 0-2). Younger age (adjusted odds ratio [aOR]: 0.965, 95% confidence interval [CI]: 0.947-0.982; p < 0.001), lower serum glucose (aOR: 0.865, 95%CI: 0.807-0.928; p < 0.001), lower baseline National Institutes of Health Stroke Scale (NIHSS) score (aOR: 0.907, 95%CI: 0.869-0.947; p < 0.001), fewer total passes (aOR: 0.791, 95%CI: 0.665-0.939; p = 0.008), shorter punctures to recanalization time (aOR: 0.995, 95%CI:0.991-0.999; p = 0.017), and modified Thrombolysis in Cerebral Infarction (mTICI) score 2b to 3 (aOR: 8.330, 95%CI: 2.705-25.653; p < 0.001) were independent predictors of good outcomes after intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke. CONCLUSION: Younger age, lower serum glucose level, lower baseline NIHSS score, fewer total passes, shorter punctures to recanalization time, and mTICI scores of 2b to 3 were independent predictors of good outcomes after intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke. CHINESE CLINICAL TRIAL REGISTRY IDENTIFIER: ChiCTR-IOR-17014167.

Analysis of rescue strategies for acute thrombosis during STA-MCA bypass surgery and the literature review.

BACKGROUND AND OBJECTIVES: STA-MCA bypass surgery is mainly used for Moyamoya disease, giant intracranial aneurysms, and resection of intracranial tumors requiring sacrifice of blood vessels. The intraoperative patency of the reconstructive vessels is critical to the efficacy of the procedure. This study aimed to evaluate the efficacy of intra-arterially infused tirofiban for the treatment of acute thrombosis during STA-MCA bypass surgery and countermeasures for acute thrombosis. METHODS: This study involved 209 patients (272 hemispheres) who underwent STA-MCA surgery between November 2020 and December 2023. Intraoperative acute thrombosis occurred in eight patients (3.83%,8 hemispheres). We retrospectively reviewed the clinical and imaging data, surgical procedure, and follow-up outcomes of eight patients. We implemented the different thrombolytic methods to evaluate the optimal thrombosis management during the bypass surgery. After three months, we assessed neurological functions using the modified Rankin Scale (mRS) and conducted a literature review using PubMed. RESULTS: Eight patients (four male patients and four female patients) developed acute thrombosis during the bypass surgery. Of the eight patients, two underwent re-anastomosis after thrombus removal, three received local injections of tirofiban into the anastomosis or the branches of the superficial temporal artery, and three underwent superselective intra-arterial tirofiban infusion using a microcatheter. Thrombosis were resolved, and arteries were recanalized in all patients. The mRS score was 0 in all patients. No major ischemic or hemorrhagic complications occurred. CONCLUSION: Our treatment methods were efficacious in the management of acute thrombosis. Intra-arterial tirofiban administration seems to be a simple and effective treatment option for acute thrombosis during STA-MCA bypass surgery.

Prehospital tirofiban increases the rate of disrupted myocardial infarction in patients with ST-segment elevation myocardial infarction: insights from the On-TIME 2 trial.

AIMS: In patients with ST-segment elevation myocardial infarction (STEMI), prehospital tirofiban significantly improved myocardial reperfusion. However, its impact on the rate of disrupted myocardial infarction (MI), particularly in the context of high-sensitivity cardiac troponin (hs-cTn) assays, is still unclear. METHODS AND RESULTS: The On-TIME 2 (Ongoing Tirofiban In Myocardial infarction Evaluation 2) trial randomly assigned STEMI patients to prehospital tirofiban or placebo before transportation to a percutaneous coronary intervention (PCI) centre. In this post hoc analysis, we evaluated STEMI patients that underwent primary PCI and had measured hs-cTn levels. Troponin T levels were collected at 18-24 and 72-96 h after PCI. Disrupted MI was defined as peak hs-cTn T levels ≤ 10 times the upper limit of normal (≤140 ng/L). Out of 786 STEMI patients, 47 (6%) had a disrupted MI. Disrupted MI occurred in 31 of 386 patients (8.0%) in the tirofiban arm and in 16 of 400 patients (4.0%) in the placebo arm (P = 0.026). After multivariate adjustment, prehospital tirofiban remained independently associated with disrupted MI (odds ratio 2.03; 95% confidence interval 1.10-3.87; P = 0.027). None of the patients with disrupted MI died during the 1-year follow-up, compared with a mortality rate of 2.6% among those without disrupted MI. CONCLUSION: Among STEMI patients undergoing primary PCI, the use of prehospital tirofiban was independently associated with a higher rate of disrupted MI. These results, highlighting a potential benefit, underscore the need for future research focusing on innovative pre-treatment approaches that may increase the rate of disrupted MI.

Safety and efficacy of tirofiban treatment in the endovascular treatment of patients with acute ischaemic stroke - A meta-analysis.

OBJECT: The use of endovascular therapy (EVT) has become a widespread strategy for the clinical management of acute ischemic stroke (AIS). However, the combination of arterial injection of tirofiban with EVT for AIS continues to be a subject of controversy. This meta-analysis was conducted to assess the safety and efficacy of this treatment approach. METHODS: Relevant studies were identified through a systematic literature search in Pubmed, EMBASE, Web of Science, and Cochrane Library databases, covering articles published from January 2010 to January 2023. The efficacy outcomes included favorable functional outcomes, recanalization rates, and safety outcomes including mortality and symptomatic intracranial hemorrhage (sICH). RESULTS: The meta-analysis consisted of data from 13 studies, which included 1 randomized controlled trial (RCT), 7 prospective cohort studies, and 5 retrospective cohort studies, encompassing a total of 3477 patients. The study results indicate that the intra-arterial (IA) tirofiban+EVT for AIS is associated with significant improvements in favorable functional outcomes (OR, 1.21; 95%CI, 1.05-1.40; P = 0.009) and recanalization rate (OR, 1.33; 95%CI, 1.06-1.65; P = 0.01), as well as significant reductions in mortality rates (OR, 0.65; 95%CI, 0.53-0.79; P = 0.0001). Subgroup analysis revealed that administering a maintenance dose of intravenous (IV) tirofiban post-EVT was significantly associated with improved functional outcomes and reduced mortality in patients. In addition, there was no increase in the incidence of sICH (OR, 0.92; 95%CI, 0.71-1.20; P = 0.54). CONCLUSION: The administration of Intra-arterial tirofiban combined with EVT is an effective and safe treatment strategy for AIS, and postoperative maintenance doses of intravenous tirofiban may be more effective than IA only.

Renal function affects the safety and efficacy of tirofiban in acute ischemic stroke thrombectomy patients.

BACKGROUND: Acute ischemic stroke poses a significant health threat, and thrombectomy has become a routine treatment. Tirofiban has emerged as a promising adjunct therapy to minimize reocclusion after thrombectomy. We aimed to investigate whether renal function influences the safety and efficacy of tirofiban in patients undergoing endovascular therapy. METHODS: Patients' clinical data collected from the stroke unit were analyzed. The modified Rankin scale score and symptomatic intracranial hemorrhage (sICH) were used as outcome measures. RESULTS: A total of 409 patients (mean age: 66.5 years, 292 males [71.4%]) were included. Tirofiban significantly improved 3-month functional outcomes (adjusted odds ratio [aOR] = 2.408, 95% confidence interval [CI] 1.120-5.175), reduced 3-month mortality (aOR = 0.364, 95% CI 0.155-0.856), and decreased the incidence of sICH (aOR = 0.339, 95% CI 0.149-0.767) in patients with estimated glomerular filtration rate (eGFR) ≥ 90 mL/min/1.73 m². However, no significant improvement in prognosis was observed with tirofiban in patients with eGFR < 90 mL/min/1.73 m². Interaction analysis suggested a potential influence of renal function on tirofiban efficacy. CONCLUSION: Renal function may impact the efficacy of tirofiban. Administration of tirofiban in direct thrombectomy patients with normal renal function is safe and improves prognosis. However, the prognostic benefits of tirofiban are limited in patients with impaired renal function.

The efficacy and safety of continuous intravenous tirofiban for acute ischemic stroke patients treated by endovascular therapy: a meta-analysis.

Introduction: Tirofiban is a non-peptide selective glycoprotein IIb/IIIa receptor inhibitor with a short half-life. The research assesses the efficacy and safety of continuous intravenous tirofiban in patients with acute ischemic stroke (AIS) undergoing endovascular therapy (ET). Methods: A systematic search of Pubmed, Embase, Web of Science, and Cochrane Library databases is conducted from inception until January 26, 2024. Eligible studies are included based on predefined selection criteria. Efficacy outcomes (favorable functional outcome and excellent functional outcome) and safety outcomes (symptomatic intracranial hemorrhage [sICH], any intracranial hemorrhage [ICH], and 90-day mortality) are calculated using odds ratios (OR) and 95% confidence intervals (CI). Results: A total of 4,329 patients from 15 studies are included in the analysis. The results indicate a significant trend toward favorable functional outcomes in the tirofiban group (OR, 1.24; 95% CI, 1.09-1.42; p = 0.001). In terms of safety outcomes, tirofiban does not increase the risk of sICH (OR, 0.90; 95% CI, 0.71-1.13; p = 0.35) or any ICH (OR, 0.97; 95% CI, 0.70-1.34; p = 0.85), but it significantly decreases 90-day mortality (OR, 0.75; 95% CI, 0.64-0.88; p = 0.0006). A subgroup analysis suggests that continuous intravenous tirofiban demonstrates better efficacy (OR, 1.24; 95% CI, 1.09-1.42; p = 0.001) for patients with AIS undergoing rescue ET with even better results when used in combination with intra-arterial and intravenous administration (OR, 1.25; 95% CI, 1.07-1.451; p = 0.005). Conclusion: Continuous intravenous tirofiban is effective and safe for patients with AIS undergoing rescue ET, particularly when combined with intra-arterial tirofiban. Systematic review registration: PROSPERO, identifier CRD42023385695.