Perioperative complications of arteriovenous tirofiban administration versus oral dual antiplatelet therapy for stent-assisted embolization treated aneurysmal subarachnoid hemorrhage: A retrospective, controlled cohort analysis.

BACKGROUND: Major perioperative complications of stent-assisted embolization treated for aneurysmal subarachnoid hemorrhage patients include the formation of thromboembolic events (TEs) and hemorrhagic events (HEs), for which antiplatelet protocols play a key role. METHODS: We conducted a single-center retrospective analysis to compare the differences between arteriovenous tirofiban administration with traditional oral dual antiplatelet therapy (DAPT). A total of 417 consecutive patients were enrolled. General clinical characteristics, as well as the perioperative ischemic and hemorrhagic events, were retracted in digital documents. Logistic regression was conducted to identify both risk and protective factors of perioperative TEs and HEs. RESULTS: Perioperative TEs occurred in 21 patients, with an overall perioperative TEs rate of approximately 5.04%; among these patients, the incidence of perioperative TEs in the tirofiban group was less than that in the DAPT group. Additionally, 66 patients developed perioperative HEs, with an incidence of approximately 15.83%; among these patients, the incidence of perioperative HEs was less than that in the DAPT group. No significant differences were seen between the two groups in terms of the mRS score at the time of discharge. CONCLUSION: This study indicated that an improved perioperative antiplatelet drug tirofiban was an independent protective factor for perioperative TEs in stent-assisted embolization of ruptured intracranial aneurysms, but it did not impart an elevated risk of perioperative HEs and had no significant effects on the near-term prognosis of the patients.

Early tirofiban versus heparin for bridging dual antiplatelet therapy in patients undergoing coronary endarterectomy combined with coronary artery bypass grafting: a multicenter randomized controlled trial protocol (the THACE-CABG trial).

BACKGROUND: For complete revascularization, patients with diffuse coronary artery disease should have a coronary endarterectomy and a coronary artery bypass graft (CE-CABG). Sadly, CE can lead to a lack of endothelium, which raises the risk of thrombotic events. Even though daily dual antiplatelet therapies (DAPT) have been shown to reduce thrombotic events, the risk of perioperative thrombotic events is high during the high-risk period after CE-CABG, and there is no consistent protocol to bridge DAPT. This trial aims to compare safety and efficacy between tirofiban and heparin as DAPT bridging strategies after CE-CABG. METHODS: In phase I, 266 patients undergoing CE-CABG will be randomly assigned to tirofiban and heparin treatment groups to compare the two treatments in terms of the primary safety endpoint, chest tube drainage in the first 24 h. If the phase I trial shows tirofiban non-inferiority, phase II will commence, in which an additional 464 patients will be randomly assigned. All 730 patients will be studied to compare major cardiovascular and cerebrovascular events (MACCEs) between the groups in the first 30 days after surgery. DISCUSSION: Given the possible benefits of tirofiban administration after CE-CABG, this trial has the potential to advance the field of adult coronary heart surgery. TRIAL REGISTRATION: chictr.org.cn, ChiCTR2200055697. Registered 6 January 2022. https://www.chictr.org.cn/com/25/showproj.aspx?proj=149451 . Current version: 20,220,620.

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.

Tirofiban combined with Aspirin in the Treatment of Acute Penetrating Artery Territory Infarction (STRATEGY): protocol for a multicentre, randomised controlled trial.

BACKGROUND: Perforating artery territorial infarction (PAI) caused by branch atheromatous disease (BAD) is prone to recurrence and early progression without an effective and well-documented antiplatelet treatment regimen. Tirofiban, an adjunctive antiplatelet agent, has shown great potential to treat acute ischaemic stroke. However, whether the combination of tirofiban and aspirin can improve the prognosis of PAI remains unclear. AIM: To explore an effective and safe antiplatelet regimen for reducing the risk of recurrence and early neurological deterioration (END) in PAI caused by BAD by comparing the tirofiban and aspirin combination with placebo and aspirin combination. METHODS: Tirofiban combined with Aspirin in the Treatment of Acute Penetrating Artery Territory Infarction (STRATEGY) trial is an ongoing multicentre, randomised, placebo-controlled trial in China. Eligible patients shall be randomly assigned to receive standard aspirin with tirofiban or placebo on the first day and standard aspirin from days 2 to 90. The primary endpoint is a new stroke or END within 90 days. The primary safety endpoint is severe or moderate bleeding within 90 days. DISCUSSION: The STRATEGY trial will assess whether tirofiban combined with aspirin is effective and safe in preventing recurrence and END in patients with PAI. TRIAL REGISTRATION NUMBER: NCT05310968.

Effects of Tirofiban in Patients with Acute Myocardial Infarction and Diabetes Mellitus undergoing Primary Percutaneous Coronary Intervention.

OBJECTIVE: This study evaluated the efficacy and safety of early vs. late tirofiban administration in the treatment of patients with acute ST-elevation myocardial infarction (STEMI) and diabetes mellitus (DM) undergoing primary percutaneous coronary intervention (pPCI). METHODS: 120 patients with STEMI and DM treated with pPCI were randomly divided into an observation group (n=60) and a control group (n=60). The observation group and the control group were intravenously injected with a bolus of tirofiban preoperatively or intraoperatively, respectively; both groups were then given an intravenous infusion over 24 h at 0.15 µg/kg/min. Thrombolysis in myocardial infarction (TIMI) grade flow, myocardial perfusion index, and functional heart parameters, as well as major adverse cardiovascular events and bleeding, were compared between the two groups. RESULTS: Functional heart parameters, including left ventricular ejection fraction and cardiac output, were significantly improved in the observation group 6 months after discharge. Thrombus aspiration, inflammatory factors, and cardiac troponin I (cTNI) were more significantly decreased in the observation group than in the control group. The sum-ST-segment elevation at 2 h after pPCI treatment in the observation group was better than that in the control group. There was no significant difference in the incidence of adverse reactions and bleeding between the two groups. CONCLUSION: The administration of tirofiban before reperfusion therapy compared with after reperfusion therapy is more effective in reducing the hyperthrombotic load, thrombus aspiration, inflammatory factors, and cTNI and can effectively improve myocardial perfusion and heart function.

Does Endovascular Thrombectomy(ET) plus tirofiban benefit stroke patients: A systematic review and meta-analysis.

BACKGROUND: Ischemic stroke is the second leading cause of death worldwide. Endovascular thrombectomy (ET) has been shown to prevent disability in a proportion of patients. The use of tirofiban in patients undergoing ET after acute stroke has resulted in improved patient function and reduced mortality to some extent. In this systematic review and meta-analysis of the current period, an overview of the most recent studies on the potential efficacy of using tirofiban to help acute stroke patients improve function and reduce mortality was provided. METHODS: In this meta-analysis, we explore the safety and efficacy of ET combined with tirofiban in patients with acute stroke. We searched the PubMed, EMBASE, Web of Science, and The Cochrane Library database from the construction of the library to the present relevant RCTs/non-RCTs. The following key words were used for finding relevant studies from the databases"tirofiban""thrombectomy"" Stroke"" balloon angioplasty""stenting". RESULTS: Total of 14 trials with 4366 individuals enrolled were included in the Meta-analysis including 2732(62.6) who received ET alone and 1634(37.4 %) who received tirofiban plus ET. The primary outcome of 90-day functional independence (modified Rankin scale (mRS) score≤2) was 42.2 % (1043/2473) in the ET alone group vs. 46.2 % (684/1480) in the tirofiban with ET group (risk ratio (RR), 1.10 [95 % CI, 1.02-1.18]; P=0.02),mortality at 90 days (RR, 0.86 [95 % CI, 0.76-0.98]; P = 0.02). There is no significant between-group differences were found in excellent outcome (mRS score ≤1) (RR, 1.08 [95 % CI, 0.95-1.23]; P = 0.22), symptomatic intracranial hemorrhage (RR, 1.11 [95 % CI, 0.92-1.34]; P = 0.27). CONCLUSIONS: These findings suggest that the use of ET combined with tirofiban in patients with acute stroke is safe and has the potential to reduce mortality and improve functional independence at 90 days.

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.

Subtyping treatment response of tirofiban in acute ischemic stroke based on neuroimaging features.

In a previously published clinical trial, we demonstrated that tirofiban was effective and safe in acute ischemic stroke (AIS) patients who did not undergo early recanalization treatments. We aimed to evaluate neuroimaging characteristics and their clinical significance to guide tirofiban treatment. In this post hoc analysis, location of infarcts (anterior circulation stroke [ACS] vs. posterior circulation stroke [PCS]), degree of cerebral artery stenosis (≤69% vs. ≥70% or occlusion), total infarct volume, and ASPECTS were used to predict the treatment effects of tirofiban, defined as the proportions of excellent and favorable functional outcome (modified Rankin Scale [mRS] score of 0-1, 0-2) at 90 days. ACS patients were more likely to achieve excellent (OR 2.08; 95% CI 1.25-3.45; p = 0.004) and favorable functional outcome (OR 2.28; 95% CI 1.24-4.22; p = 0.008) when treated with tirofiban. However, there was no significant difference in PCS patients between tirofiban and the control group. For patients with severe stenosis (≥70% or occlusion), tirofiban treatment improved the proportion of good outcomes (OR 2.84; 95% CI 1.44-5.60; p = 0.002 for mRS 0-1; OR 2.42; 95% CI 1.22-4.77; p = 0.011 for mRS 0-2). Meanwhile, we found that tirofiban improved outcome in patients with ASPECTS 8-10 and was independent of total infarct volume. These findings support the hypothesis that patients with ACS and severe stenosis may be recommended for tirofiban treatment, which can be predicted independent of total infarct volume.

Effects of tirofiban on large vessel occlusion stroke are modified by etiology and renal function.

OBJECTIVE: Renal function can modify the outcomes of large vessel occlusion (LVO) stroke across stroke etiologies in disparate degrees. The presence of renal function deficit can also impair the pharmacokinetics of tirofiban. Hence, this study aimed to investigate the roles of renal function in determining efficacy and safety of intravenous tirofiban before endovascular treatment (EVT) for acute ischemic stroke patients with large vessel occlusion (LVO). METHODS: This study was a post hoc exploratory analysis of the RESCUE-BT trial. The primary outcome was the proportion of patients achieving functional independence (modified Rankin scale 0-2) at 90 days, and the primary safety outcome was the rate of symptomatic intracranial hemorrhage (sICH). RESULTS: Among 908 individuals with available serum creatinine, decreased estimated glomerular filtration rate (eGFR) status was noted more commonly in patients with cardioembolic stroke (CE), while large artery atherosclerosis (LAA) was predominant in patients with normal renal function. In LAA with normal renal function, tirofiban was associated with higher rates of functional independence at 90 days (41.67% vs 59.80%, p = 0.003). However, for LVO patients with renal dysfunction, tirofiban did not improve functional outcomes for any of the etiologies (LAA, p = 0.876; CE, p = 0.662; others, p = 0.894) and significantly increased the risk of sICH among non-LAA patients (p = 0.020). Mediation analysis showed tirofiban reduced thrombectomy passes (12.27%) and drug/placebo to recanalization time (14.25%) mediated its effects on functional independence. CONCLUSION: This present study demonstrated the importance of evaluating renal function before administering intravenous tirofiban among patients with LVO who are planned to undergo EVT.

Efficacy and safety of tirofiban combined with endovascular therapy for basilar artery occlusion stroke due to large artery atherosclerosis.

BACKGROUND: This study aimed to evaluate the efficacy and safety of adjuvant tirofiban in patients with acute basilar artery occlusion due to large-artery atherosclerotic (LAA) receiving endovascular therapy (EVT). METHODS: This was a non-randomized, multicenter study using data from the Endovascular Treatment for Acute BASILAR Artery Occlusion (BASILAR) registry. Patients with acute basilar artery occlusion due to LAA within 24h of symptom onset who underwent EVT were included. Patients were divided into tirofiban and non-tirofiban groups according to whether tirofiban was used. The primary outcome was the ordinal modified Rankin scale score at 90 days. Safety outcomes were mortality within 90 days and symptomatic intracranial hemorrhage (sICH) within 48 h. RESULTS: A total of 417 patients were included, of whom 275 patients were in the tirofiban group and 142 patients in the non-tirofiban group. Compared with patients in the non-tirofiban group, patients in the tirofiban group were associated with a favorable shift in functional outcome at 90 days (6[4-6] vs 5 [2-6]; adjusted common OR, 2.51; 95 % CI, 1.64-3.83). The mortality was lower in the tirofiban group than the non-tirofiban group (40.7 % vs 58.5 %; adjusted OR, 0.35; 95 % CI, 0.21-0.56). The rate of sICH was 12.2 % in the non-tirofiban group and 5.2 % in the tirofiban group (adjusted OR, 0.37; 95 % CI, 0.17-0.80; P = 0.012). CONCLUSION: Tirofiban plus EVT might improve functional outcomes with a good safety for patients with acute basilar artery occlusion due to LAA. The results need to be confirmed in a randomized trial.

A case report of acute myocardial infarction with extremely severe thrombocytopenia after percutaneous coronary intervention.

INTRODUCTION: The case report's purpose is to remind doctors a rare complication named thrombocytopenia of antithrombotic drugs. As a result, severe bleeding or even life-threatening situations may be avoided. PATIENT CONCERNS: A specific case of a patient with acute myocardial infarction, a significant decrease in platelet count was observed after percutaneous coronary intervention. DIAGNOSIS: After ruling out other potential causes, the medical team considered tirofiban-induced thrombocytopenia as a possible explanation. INTERVENTIONS AND OUTCOMES: Through careful monitoring and adjustment of medication, the patient's platelet count eventually returned to normal. CONCLUSION: To ensure patient safety, it is advised to regularly monitor platelet counts at intervals of 2 to 6 hours before and after administering tirofiban.

Efficacy and safety of tirofiban in patients with acute ischemic stroke treated with endovascular thrombectomy: A frequentist and Bayesian meta-analysis.

BACKGROUND: Tirofiban is an antiplatelet treatment approved for acute coronary syndrome, but it has not been rigorously evaluated for efficacy and safety in patients with acute ischemic stroke (AIS) treated with endovascular thrombectomy (EVT). METHODS: Electronic databases were systematically searched for studies conducted from January 1, 2015, to July 31, 2021, that evaluated tirofiban administration for patients with AIS treated with EVT in comparison with control. Risk ratios (RRs) and confidence intervals (CIs) were estimated for favorable functional outcomes (FFOs), mortality, and symptomatic intracranial hemorrhage (SICH), each 90 days after AIS. Bayesian hierarchical modeling was performed to obtain posterior RR and its 95% highest posterior density (HPD) for validation. RESULTS: Compared with controls, tirofiban users exhibited increased FFOs (RR, 1.18; 95% CI, 1.08-1.30), decreased mortality (RR, 0.77; 95% CI, 0.64-0.92), and no difference in SICH (RR, 0.97; 95% CI, 0.77-1.23). Tirofiban users in the postbolus infusion subgroup exhibited increased FFOs (RR, 1.20; 95% CI, 1.07-1.35), decreased mortality (RR, 0.71; 95% CI, 0.58-0.88), and no increase in SICH (RR, 0.97; 95% CI, 0.72-1.29). The bolus-only subgroup showed no differences in FFO, mortality, or SICH between the tirofiban and control groups. Consistent results were obtained for posterior density of FFO (posterior RR, 1.20; 95% HPD, 1.06-1.34), mortality (posterior RR, 0.77; 95% HPD, 0.63-0.92), and SICH (posterior RR, 0.98; 95% HPD, 0.71-1.26). CONCLUSION: For patients with AIS treated with EVT, tirofiban improved FFOs, decreased mortality, and did not increase SICH compared with controls; postbolus infusion for administering tirofiban was more favored than the bolus-only regimen.

Severe thrombocytopenia induced by tirofiban after percutaneous coronary intervention: a case report.

BACKGROUND: Tirofiban is a nonpeptide glycoprotein IIb/IIIa receptor antagonist used widely in patients subjected to percutaneous coronary intervention. While the usage of tirofiban sets an important clinical benefit, severe thrombocytopenia can occur with use of this agent. CASE PRESENTATION: A 76-year-old Chinese man was admitted with 1-month history of sudden onset of chest tightness. He was diagnosed as having subacute inferior myocardial infarction, and percutaneous coronary intervention was performed. After the procedure, patient received tirofiban at 0.15 µg/kg/minute for 4 h. A blood sample was obtained for a complete blood count; severe thrombocytopenia was reported according to routine orders at our hospital. All antiplatelet drugs including tirofiban, aspirin, and clopidogrel were immediately discontinued. The patient received platelet transfusions and was treated with immunoglobulin G. Two days later, the patient's platelet count had increased to 75 × 109/L. There was a significant improvement after day 5, and the platelet count was 112 × 109/L. Seven days after the acute thrombocytopenia, he was discharged with normal platelet count. CONCLUSIONS: Clinicians should be particularly aware of tirofiban-induced thrombocytopenia in routine practice.

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.

Intravenous tirofiban following successful reperfusion in intracranial large artery atherosclerotic stroke: A secondary analysis of a randomized clinical trial.

OBJECTIVE: This study aimed to investigate whether treatment with adjunct intravenous tirofiban is associated with improved outcomes following successful reperfusion in patients with intracranial atherosclerotic stroke. METHODS: Patients with intracranial large artery atherosclerotic (LAA) stroke and an expanded Treatment in Cerebral Ischemia angiographic score of 2b50 to 3 from the Effect of Intravenous Tirofiban versus Placebo Before Endovascular Thrombectomy on Functional Outcomes in Large Vessel Occlusion Stroke (RESCUE BT) trial were included. The primary outcome was the difference in proportion of independent functional outcome (modified Rankin score of 0-2 at 90 days). Safety outcomes included the rates of symptomatic intracranial hemorrhage (sICH) and 90-day mortality. RESULTS: Among the 382 patients with intracranial LAA stroke and successful reperfusion, 175 patients (45.8%) were treated with intravenous tirofiban and 207 (54.2%) with placebo. The proportion of patients with independent functional outcome at 90 days was 54.3% (95 out of 175) with tirofiban and 44.0% (91 out of 207) with placebo (adjusted odds ratio [aOR], 1.58; 95% CI, 1.02-2.44; p = 0.04). Intravenous tirofiban was not significantly associated with an increased risk of sICH (12/175 [6.9%] vs. 11/207 [5.3%]; aOR, 1.41; 95% CI, 0.59-3.34; p = 0.44) or 90-day mortality (21/175 [12.0%] vs. 34/207 [16.4%]; aOR, 0.71; 95% CI, 0.38-1.31; p = 0.27). INTERPRETATION: Among patients with acute intracranial LAA stroke and successful reperfusion following endovascular thrombectomy, adjunct intravenous tirofiban was associated with a higher rate of independent functional outcome, without higher rates of sICH or mortality. Confirmatory randomized trials in these patients are desirable.

Safety and efficacy of tirofiban in the management of stroke: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: About 30 % of stroke patients have experienced unsuccessful reperfusion following endovascular therapy. Mechanical thrombectomy instruments may contribute to this by stimulating platelet aggregation. Tirofiban is a selective and rapidly activated antagonist of the platelets nonpeptide glycoprotein IIb/IIIa receptors that can reversibly suppress platelet aggregation. But, data from the medical literature are conflicting regarding its safety and efficacy for stroke patients. Hence, this study was designed to assess the safety and efficacy of tirofiban in stroke patients. METHODS: Five major databases (PubMed, Scopus, Web of Science, Embase, and Cochrane library) were searched till December 2022. The Cochrane tool was used for risk of bias assessment, and the RevMan 5.4 was utilized for data analysis. RESULTS: Seven RCTs with 2088 stroke patients were included. Tirofiban significantly increased the number of patients with mRS 0 score after 90 days than control; RR= 1.39, 95 %CI [1.15, 1.69]; p = 0.0006. Additionally, it reduced the NIHSS score after seven days; MD= -0.60, 95 %CI [-1.14, -0.06]; p = 0.03. However, tirofiban increased the incidence of intracranial haemorrhage (ICH); RR= 1.22, 95 %CI [1.03, 1.44]; p = 0.02. Other assessed outcomes showed insignificant results. CONCLUSIONS: Tirofiban was associated with a higher mRS 0 score after three months and a lower NIHSS score after seven days. However, it is associated with higher ICH. Multicentric trials are required to provide more convincing proof of its utility.

Tirofiban-induced thrombocytopenia.

Tirofiban is a small non-peptide ligand-mimetic Glycoprotein (GP) IIb/IIIa inhibitor which can reversibly bind to the arginine-glycine-aspartic acid (RGD) recognition site of GP IIb/IIIa to prevent platelet aggregation. It reduces the incidence of thrombotic cardiovascular events in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Although generally considered safe, tirofiban has been reported to be associated with thrombocytopenia in several case reports and clinical trials. The pathogenesis for this adverse reaction is not entirely understood, is thought to be due to immune-mediated reaction. This side effect caused by tirofiban is especially concerning given how frequently it is used in the practice of contemporary cardiovascular care. The present review provides an overview of the pathophysiology, clinical presentation, management, and risk factors associated with tirofiban-induced thrombocytopenia.

Tirofiban-induced thrombocytopenia usually occurred within the first 24 h of treatment, frequently accompanied by bleeding symptoms. The majority of the time, supportive care is used to manage this adverse event, and the platelet count often returns to normal in a few days.Although the exact cause of this adverse response is unknown, it is thought to be due to drug-dependent antibodies that bind to GP IIb/IIIa, presumably after tirofiban-induced conformational change.Age ≥ 65 years, white blood cell ≥ 12 × 10⁹/L, diabetes mellitus, congestive heart failure, and chronic kidney disease were identified as the risk factors for tirofiban-induced thrombocytopenia. Further investigations are needed for this.

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.).

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.