Platelet integrin αIIbß3 plays a key role in a venous thrombogenesis mouse model.

Venous thrombosis (VT) is a common vascular disease associated with reduced survival and a high recurrence rate. VT is initiated by the accumulation of platelets and neutrophils at sites of endothelial cell activation. A role for platelet αIIbß3 in VT is not established, a task complicated by the increased bleeding risk caused by partial agonists such as tirofiban. Here, we show that m-tirofiban, a modified version of tirofiban, does not agonize αIIbß3 based on lack of neoepitope expression and the cryo-EM structure of m-tirofiban/full-length αIIbß3 complex. m-tirofiban abolishes agonist-induced platelet aggregation while preserving clot retraction ex vivo and, unlike tirofiban, it suppresses venous thrombogenesis in a mouse model without increasing bleeding. These findings establish a key role for αIIbß3 in VT initiation and suggest that m-tirofiban and compounds with a similar structurally-defined mechanism of action merit consideration as potential thromboprophylaxis agents in patients at high risk for VT and hemorrhage.

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.

Tirofiban-induced diffuse alveolar haemorrhage.

A middle-aged man presented with inferior wall ST-elevation myocardial infarction and underwent primary percutaneous coronary intervention with tirofiban administered due to extensive thrombus. He developed sudden-onset dyspnoea, bilateral crepitations, haemoptysis, desaturation and hypotension an hour after starting tirofiban infusion. The tirofiban, antiplatelet medications and heparin were stopped immediately. Chest X-ray showed patchy opacities in the left upper, middle and lower zones. High-resolution CT showed confluent areas of consolidation with surrounding ground glass opacities and interlobular septal thickening (crazy pavement appearance) representing diffuse alveolar haemorrhage (DAH). He was managed with inotropes, non-invasive ventilation and intravenous furosemide. He was asymptomatic with complete resolution of lung opacities in chest X-ray done 2 months follow-up. DAH is a rare but potentially life-threatening complication which is often misidentified with other respiratory syndromes. Treatment includes stopping tirofiban and anticoagulant medication, blood transfusion, and institution of mechanical ventilation.

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.

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.

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.

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.

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.

Efficacy and safety of tirofiban in patients with acute branch atheromatous disease-related stroke (BRANT): a protocol for a randomised controlled trial.

INTRODUCTION: Branch atheromatous disease (BAD)-related stroke is increasingly becoming a clinical entity and prone to early neurological deterioration (END) and poor prognosis. There are no effective regimens to reduce the disability caused by BAD-related stroke in acute phase. Recent studies have indicated the efficacy of tirofiban in acute ischaemic stroke; however, its efficacy has not been validated in patients with BAD-related stroke. Thus, we aim to test whether intravenous tirofiban initiated within 48 hours after the onset would improve the functional outcome in patients with acute BAD-related stroke, in comparison with the standard antiplatelet therapy based on the current guideline. METHODS AND ANALYSIS: BRANT is a multicentre, randomised, open-label, blinded endpoint, parallel-controlled, phase III trial conducted in 21 hospitals in China. Participants aged 18-75 years with acute BAD-related stroke within 48 hours after the stroke onset are randomised in a 1:1 ratio to the tirofiban or control group. The treatment period is 48 hours in both groups. The primary outcome is the excellent functional outcome (modified Rankin Scale Score: 0-1) at 90 days. The secondary outcomes include END, major bleeding, stroke, death, functional status, serious adverse events and change in bleeding-related markers. Assuming the rates of the primary outcome to be 74% in the tirofiban group and 62% in the control group, a total of 516 participants are needed for 0.8 power (two-sided 0.05 alpha). ETHICS AND DISSEMINATION: BRANT study has been approved by the Ethics Committee of the Peking Union Medical College Hospital (I-23PJ1242). Written informed consent is required for all the patients before enrolment. The results of the study will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT06037889).

Association of functional outcomes between intravenous tirofiban and endovascular thrombectomy in imaging-screened patients with large vessel occlusion stroke: a secondary analysis of randomized clinical trial.

BACKGROUND: In the RESCUE BT (endovascular treatment with versus without tirofiban for stroke patients with large vessel occlusion) trial, enrollment in extended time window was based on noncontrast computed tomography. To assess whether perioperative intravenous tirofiban would further enhance the clinical benefit of endovascular therapy in the RESCUE BT trial according to advanced imaging criteria based on current American Heart Association/American Stroke Association (AHA/ASA) guidelines. METHODS: This is a secondary analysis of the RESCUE BT trial. Patients who were eligible for endovascular thrombectomy in the 6 h window and met the criteria of the DAWN or DEFUSE 3 trials in the extended window according to the AHA/ASA guidelines were analyzed. The primary outcome was the distribution of the 90-day modified Rankin Scale (mRS) scores. Safety outcomes included the incidence of symptomatic intracranial hemorrhage (sICH) within 48 h and 90-day mortality. RESULTS: A total of 652 patients (319 in tirofiban group and 333 in placebo group) who meeting the AHA/ASA guidelines were included in this analysis, with median interquartile ranges (IQR) age of 68 (58-75) years, 278 (42.6%) were women. The median 90-day mRS score was 3 (IQR, 1-4) in the tirofiban group, and 3 (IQR, 1-4) in the placebo group. The adjusted common odds ratio (OR) for a lower level of disability with tirofiban than with placebo was 1.08 (95% CI: 0.83-1.42). The incidence of sICH [10.1% versus 6.3%; adjusted OR 1.70; (95% CI: 0.95-3.04)] was not significantly different between groups. However, intravenous tirofiban might be associated with lower disability level [adjusted common OR, 1.74 (95% CI: 1.14-2.65); P =0.01] in patients with large artery atherosclerosis. CONCLUSIONS: There was no significant difference in the severity of disability at 90 days with intravenous tirofiban compared to placebo in patients who underwent endovascular therapy according to AHA/ASA guidelines. The authors observed potential benefits of tirofiban in patients with large artery atherosclerosis, but there was an increased risk of sICH in patients with cardioembolism stroke.

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.

Effects of Tirofiban on Neurological Deterioration in Patients With Acute Ischemic Stroke: A Randomized Clinical Trial.

Importance: Evidence supports using antiplatelet therapy in patients with acute ischemic stroke. However, neurological deterioration remains common under the currently recommended antiplatelet regimen, leading to poor clinical outcomes. Objective: To determine whether intravenous tirofiban administered within 24 hours of stroke onset prevents early neurological deterioration in patients with acute noncardioembolic stroke compared with oral aspirin. Design, Setting, and Participants: This investigator-initiated, multicenter, open-label, randomized clinical trial with blinded end-point assessment was conducted at 10 comprehensive stroke centers in China between September 2020 and March 2023. Eligible patients were aged 18 to 80 years with acute noncardioembolic stroke within 24 hours of onset and had a National Institutes of Health Stroke Scale (NIHSS) score of 4 to 20. Intervention: Patients were assigned randomly (1:1) to receive intravenous tirofiban or oral aspirin for 72 hours using a central, web-based, computer-generated randomization schedule; all patients then received oral aspirin. Main Outcome: The primary efficacy outcome was early neurological deterioration (increase in NIHSS score ≥4 points) within 72 hours after randomization. The primary safety outcome was symptomatic intracerebral hemorrhage within 72 hours after randomization. Results: A total of 425 patients were included in the intravenous tirofiban (n = 213) or oral aspirin (n = 212) groups. Median (IQR) age was 64.0 years (56.0-71.0); 124 patients (29.2%) were female, and 301 (70.8%) were male. Early neurological deterioration occurred in 9 patients (4.2%) in the tirofiban group and 28 patients (13.2%) in the aspirin group (adjusted relative risk, 0.32; 95% CI, 0.16-0.65; P = .002). No patients in the tirofiban group experienced intracerebral hemorrhage. At 90-day follow-up, 3 patients (1.3%) in the tirofiban group and 3 (1.5%) in the aspirin group died (adjusted RR, 1.15; 95% CI, 0.27-8.54; P = .63), and the median (IQR) modified Rankin scale scores were 1.0 (0-1.25) and 1.0 (0-2), respectively (adjusted odds ratio, 1.28; 95% CI, 0.90-1.83; P = .17). Conclusions and Relevance: In patients with noncardioembolic stroke who were seen within 24 hours of symptom onset, tirofiban decreased the risk of early neurological deterioration but did not increase the risk of symptomatic intracerebral hemorrhage or systematic bleeding. Trial Registration: ClinicalTrials.gov Identifier: NCT04491695.

Intravenous antiplatelet therapy in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention : A report from the INVEST-STEMI group.

The use of intravenous antiplatelet therapy during primary percutaneous coronary intervention (PPCI) is not fully standardized. The aim is to evaluate the effectiveness and safety of periprocedural intravenous administration of cangrelor or tirofiban in a contemporary ST-segment elevation myocardial infarction (STEMI) population undergoing PPCI. This was a multicenter prospective cohort study including consecutive STEMI patients who received cangrelor or tirofiban during PPCI at seven Italian centers. The primary effectiveness measure was the angiographic evidence of thrombolysis in myocardial infarction (TIMI) flow < 3 after PPCI. The primary safety outcome was the in-hospital occurrence of BARC (Bleeding Academic Research Consortium) 2-5 bleedings. The study included 627 patients (median age 63 years, 79% males): 312 received cangrelor, 315 tirofiban. The percentage of history of bleeding, pulmonary edema and cardiogenic shock at admission was comparable between groups. Patients receiving cangrelor had lower ischemia time compared to tirofiban. TIMI flow before PPCI and TIMI thrombus grade were comparable between groups. At propensity score-weighted regression analysis, the risk of TIMI flow < 3 was significantly lower in patients treated with cangrelor compared to tirofiban (adjusted OR: 0.40; 95% CI: 0.30-0.53). The risk of BARC 2-5 bleeding was comparable between groups (adjusted OR:1.35; 95% CI: 0.92-1.98). These results were consistent across multiple prespecified subgroups, including subjects stratified for different total ischemia time, with no statistical interaction. In this real-world multicenter STEMI population, the use of cangrelor was associated with improved myocardial perfusion assessed by coronary angiography after PPCI without increasing clinically-relevant bleedings compared to tirofiban.

Impact of rise and fall phases of shear on platelet activation and aggregation using microfluidics.

Blood flow disorders are often the result of the non-physiological narrowing of blood arteries caused by atherosclerosis and thrombus. The blood then proceeds through rising-peak-decreasing phases as it passes through the narrow area. Although abnormally high shear is known to activate platelets, the shear process that platelets undergo in small arteries is complex. Thus, understanding how each shear phase affects platelet activation can be used to improve antiplatelet therapy and decrease the risk of side effects like bleeding. Blood samples were sheared (68.8 ms,5200 s-1) in vitro by the microfluidic technique, and platelet activation levels (P-selectin and integrin αIIbß3) and von Willebrand factor (vWF) binding to platelets were analyzed by flow cytometry. Post-stenosis platelet aggregation was dynamically detected using microfluidic technology. We studied TXA2, P2Y12-ADP, and integrin αIIbß3-fibrinogen receptor pathways by adding antiplatelet drugs, such as acetylsalicylic acid (ASA, an active ingredient of aspirin that inhibits platelet metabolism), ticagrelor (hinders platelet activation), and tirofiban (blocks integrin αIIbß3 receptor) in vitro, respectively, to determine platelet activation function mediated by transient non-physiological high shear rates. We demonstrated that platelets can be activated under transient pathological high shear rates. The shear rise and fall phases influenced shear-induced platelet activation by regulating the binding of vWF to platelets. The degree of platelet activation and aggregation increased with multiple shear rise and fall phases. ASA did not inhibit shear-mediated platelet activation, but ticagrelor and tirofiban effectively inhibited shear-mediated platelet activation. Our data demonstrated that the shear rise and fall phases play an important role in shear-mediated platelet activation and promote platelet activation and aggregation in a vWF-dependent manner. Blocking integrin αIIbß3 receptor and hindering P2Y12-ADP were beneficial to reducing shear-mediated platelet activation.

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.

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.

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.

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.