Analysis of the Inhibitory Effect of Tirofiban on Shear-Induced Platelet Aggregation by Microfluidic Technique / 医用生物力学

Objective To observe the inhibitory effect of Tirofiban on different shear-induced platelet aggregation, and to provide medication suggestions for the treatment of thrombosis in different hemodynamic environment. Methods Polydimethylsiloxane ( PDMS)-glass microchannel chips were fabricated by soft lithography. The whole blood of healthy volunteers anticoagulated with sodium citrate was collected and incubated with different concentrations of Tirofiban in vitro. The blood flowed through the straight microchannel or channel with 80% narrow for 150 seconds at the speed of 11 μL/ min and 52 μL/ min, respectively. The wall shear stress rates in straight channel at 11 μL/ min and 52 μL/ min were 300 s-1 and 1 500 s-1, respectively. The maximum wall shear rates in the channel with 80% occlusion at 11 μL/ min and 52 μL/ min were 1 600 s-1 and 7 500 s-1, respectively. The adhesion and aggregation images of fluorescent labeled platelets on glass surface were photographed with the microscope, and the fluorescent images were analyzed with Image J. The platelet surface coverage ratio was used as a quantitative index of platelet aggregation behavior, and the IC50 of Tirofiban for platelet inhibition was calculated under different shear rates. Flow cytometry was used to detect the platelet activation index (CD62P, PAC-1) in the whole blood at 52 μL/ min in channel with 80% occlusion. Results Tirofiban inhibited platelet aggregation in a dose-dependent manner, and the inhibitory effect was related to the shear rate. Under the shear rates of 11 μL/ min and 52 μL/ min, the aggregation was almost completely inhibited when the concentration in straight channel reached 100 nmol / L. When the concentration in channels with 80% occlusion reached 1 μmol / L, the aggregation was almost completely inhibited. IC50 values at 11 μL/ min and 52 μL/ min in straight channel were 2. 3 nmol / L and 0. 5 nmol / L, respectively. IC50 values at 11 μL/ min and 52 μL/ min in channels with 80% occlusion were 20. 73 nmol / L and 4. 5 nmol / L. Pathologically high shearforce induced an increase in platelet activation, which could be inhibited by Tirofiban. Conclusions Tirofiban can effectively inhibit shear-induced platelet aggregation, and different concentrations of Tirofiban should be given according to the thrombus formed in different shear force environment in clinic practice

Diagnosis and treatment recommendations and case study of severe thrombocytopenia caused by tirofiban / 中国输血杂志

【Objective】 To investigate the clinical manifestations, diagnosis, differential diagnosis and management strategies of thrombocytopenia caused by tirofiban. 【Methods】 The basic clinical data, platelet count changes and treatment course of 7 patients with acute coronary syndrome who used tirofiban resulting in severe thrombocytopenia during their hospitalization in our hospital from December 2021 to March 2023 were collected, and their individual and common characteristics were analyzed. 【Results】 Platelet counts were in the normal range in all 7 patients on admission. Six of the patients had thrombocytopenia occurring from 3 to 16 hours after tirofiban use, and one patient was detected at 34 h of tirofiban use. Their minimum platelet count ranged from (1-11)×109/L. All 7 cases discontinued tirofiban and other antithrombotic drugs, and the platelet count increased to 50×109/L in 6 patients in 2 to 4 days after stopping the drug and gradually returned to the normal range. During this period, there were no bleeding or acute thrombotic events, and no platelet transfusion was conducted. Five patients resumed antithrombotic therapy when the platelet count returned to (20-50)×109/L, 1 patient underwent elective coronary artery bypass grafting (CABG) surgery when the count rose above 50×109/L. One patient had bleeding manifestations after thrombocytopenia and required limited-duration CABG surgery, so 3 U platelet transfusion and immunoglobulin treatment were performed consecutively. CABG surgery was performed when the platelet count increased to 76×109/L. The differential diagnosis of the cause of thrombocytopenia was performed in all seven patients, and other causes of thrombocytopenia, such as heparin, were excluded. 【Conclusion】 Tirofiban can cause acute severe or extremely severe thrombocytopenia. Routine platelet count testing at 6 hours after medication can prevent serious adverse events by discontinuing tirofiban promptly after thrombocytopenia occurs. At the same time, it is determined whether to perform platelet transfusion based on whether the patient has bleeding and the risk of bleeding, and the timing of resuming antithrombotic treatment is determined based on the recovery of platelet count and the risk of thrombosis.

Efficacy and safety of intravenous tirofiban after endovascular therapy in patients with intracranial atherosclerotic stroke / 国际脑血管病杂志

Objective:To investigate the efficacy and safety of intravenous tirofiban after endovascular therapy in patients with acute intracranial large atherosclerotic stroke.Methods:Patients with acute intracranial large atherosclerotic stroke received endovascular therapy in the Stroke Center, Nanjing Drum Tower Hospital from January 2018 to December 2020 were enrolled. The incidence of symptomatic intracranial hemorrhage in patients of tirofiban group and non-tirofiban group during perioperative period and the outcome after procedure at 90 d were analyzed.Results:A total of 172 patients were included. Their average age was 66.0 years and 126 patients were male (73.3%). Ninety-two patients (53.5%) used tirofiban, and 120 (69.8%) had good outcomes. Compared with the non-tirofiban group, the tirofiban group had a significantly higher rate of good outcome at 90 d after procedure (77.2% vs. 61.3%; P=0.023). The reocclusion rate was significantly lower (7.6% vs. 18.8%; P=0.039), while there was no statistically significant difference in the incidence of symptomatic intracranial hemorrhage during periprocedureal period (4.3% vs. 3.8%; P=0.990). There was a significant independent correlation between the use of tirofiban intravenously and the good outcome at 90 d after procedure, both in the overall patients (odds ratio 0.208, 95% confidence interval 0.064-0.680; P=0.009) and the patients with severe stroke (odds ratio 0.181, 95% confidence interval 0.050-0.658; P=0.009) were all the same. Conclusion:For patients with acute intracranial large atherosclerotic stroke who received intravascular therapy, intravenous tirofiban can significantly improve the clinical outcome at 90 d after procedure, and will not increase the risk of symptomatic intracranial hemorrhage.

Sequential treatment with tirofiban and argatroban in acute isolated pontine infarction caused by branch atheromatous disease / 国际脑血管病杂志

Objective:To investigate the efficacy and safety of sequential treatment with tirofiban and argatroban in acute isolated pontine infarction (AIPI) caused by branch atheromatous disease (BAD).Methods:Consecutive patients with AIPI caused by BAD within 48 h of onset and admitted to Zhengzhou Central Hospital from April 2021 to April 2022 were enrolled retrospectively. The patients were divided into sequential treatment group and tirofiban group according to their therapeutic modalities. In the tirofiban group, tirofiban was pumped intravenously within 48 h after admission, and dual antiplatelet therapy with aspirin and clopidogrel was added 4 h before tirofiban was discontinued. On the basis of tirofiban treatment, the sequential treatment group was followed by argatroban for 5 days when tirofiban is discontinued. The main outcome measure was the modified Rankin Scale (mRS) score at 3 months after the onset . A score of <2 was defined as a good outcome. The secondary outcome measure was all the adverse events during the treatment and follow-up. Multivariate logistic regression analysis was used to determine the independent factors of the outcomes. Results:A total of 64 patients with AIPI caused by BAD were enrolled, including 32 in the sequential treatment group and 32 in the tirofiban group. There was no statistical difference in baseline data between the two groups, but the rate of good outcomes at 3 months after onset in the sequential treatment group was significantly higher than that in the tirofiban group (78.1% vs. 50.0%; χ2=5.497, P=0.019). Multivariate logistic regression analysis showed that after adjusting for low-density lipoprotein cholesterol, the higher baseline National Institutes of Health Stroke Scale score was independently associated with the poor outcomes (odds ratio 2.067, 95% confidence interval 1.343-3.182; P=0.001), while the sequential treatment was independently associated with the good outcomes (odds ratio 0.248, 95% confidence interval 0.064-0.957; P=0.043). Conclusion:Early application of sequential treatment with tirofiban and argatroban in AIPI caused by BAD may effectively improve the outcomes of patients, and the safety is good.

Safety and efficacy of intra-arterial tirofiban infusion in patients with acute cardiogenic cerebral embolism undergoing endovascular reperfusion therapy / 中华内科杂志

Objective:To evaluate the safety and efficacy of intra-arterial tirofiban infusion during endovascular reperfusion therapy in patients with acute cardiogenic cerebral embolism.Methods:Clinical data of 72 patients with acute cardiogenic cerebral embolism caused by large artery occlusion were retrospectively analyzed in Department of Neurology, Strategic Support Force Medical Center from August 2015 to August 2020.Among those, 52 patients were treated with intra-arterial tirofiban, the other 20 patients were treated with control medication. The baseline characteristics, modified thrombolysis in cerebral infarction (mTICI) score of responsible vessels, modified Rankin scale (mRS) score 90 days after operation, incidence of symptomatic intracranial hemorrhage and mortality were evaluated and compared in two groups.Results:The proportion of effective recanalization of the offending vessels (mTICI≥2b) in tirofiban group was higher than that in control group (92.3% vs. 75.0%), but the difference was not statistically significant ( P=0.104). At 90 days after operation, the rate of patients with good prognosis (mRS≤2) in tirofiban group (61.5%) was significantly higher than that in control group (35.0%) ( P<0.05). The incidence of symptomatic intracranial hemorrhage and mortality were comparable between the two groups ( P>0.05). Conclusion:Intra-arterial tirofiban infusion in patients with acute cardiogenic cerebral embolism is effective and feasible, which improves the prognosis without increasing the risk of intracranial bleeding complications.

Tirofiban interferes with antibody-mediated transfusion-related acute lung injury by inhibiting platelet-neutrophil binding / 中国输血杂志

【Objective】 To explore the feasibility of tirofiban, a platelet surface glycoprotein (GP)Ⅱb/Ⅲa receptor antagonist intervene in transfusion-related acute lung injury (TRALI), by inhibiting platelet activation and by preventing platelet and neutrophil binding to form aggregates. 【Methods】 1) Fifty wild-type male Balb/c mice, aged 8 to 10 weeks, were randomly divided into TRALI, normal, tirofiban TRALI intervention, isotype control and tirofiban normal intervention groups. In the TRALI model, tirofiban TRALI intervention and isotype control groups, each mouse was injected intraperitoneally with lipopolysaccharide (LPS) 0.1 mg/kg, and after 18 h with 4.5 mg/kg anti-MHC-I or IgG2a isotype control antibody, in which 0.5 μg/g tirofiban was injected 30 min before anti-MHC-I injection, and was labeled as tirofiban TRALI intervention. The group without any treatment was set as normal group. The tirofiban normal intervention group was injected with only 0.5 μg/g tirofiban into the tail vein, 30 min before the injection of anti-MHC-I. 2) After antibody injection, the mice were observed for 2 h, then executed with their lungs removed, and the extent of lung injury and the intervention effect of tirofiban were analyzed by comparing the differences in lung dry to wet ratio, total protein, myeloperoxidase (MPO), inflammatory factors and quantitative results of HE staining. The platelet activation level in whole blood and immunofluorescence (IF) quantification of platelet and neutrophil fluorescence were detected by flow cytometry to analyze the mechanism of tirofiban on TRALI. 【Results】 1) The indexes of lung injury in the tirofiban TRALI intervention group and TRALI model group for HE staining were 0.663 3±0.141 9 vs. 0.173 3±0.120 4 (P<0.05), respectively; 2) Platelet activation levels(%)in whole blood in the TRALI group, normal group and tirofiban TRALI intervention group were 22.87±9.943 vs 5.070±2.234 vs 5.767±3.224(P<0.05), respectively. 3) The mean fluorescence density of platelet neutrophil aggregates for IF detection in the tirofiban intervention group and TRALI model group was 21.89±3.536 vs. 32.77±0.9624 (P<0.05). 【Conclusion】 The platelet GP Ⅱ b/Ⅲa-specific inhibitor tirofiban inhibited platelet-neutrophil binding in mice, thus could possibly intervene in TRALI.

Eficácia e segurança da ponte de tirofiban como alternativa à suspensão da terapia antiplaquetária dupla em pacientes submetidos à cirurgia: uma revisão sistemática / Efficacy and safety of tirofiban bridge as an alternative to suspension of dual antiplatelet therapy in patients undergoing surgery: a systematic review

Resumo A ponte de tirofiban é uma alternativa à suspensão da terapia antiplaquetária dupla no perioperatório de pacientes com alto risco de trombose de stent e de sangramento. Objetivamos avaliar a eficácia e a segurança deste protocolo em pacientes submetidos à cirurgia em até 12 meses após intervenção coronária percutânea com stent. Realizamos uma revisão sistemática por meio de pesquisa nas bases PubMed, Web of Science, Cochrane, EMBASE, LILACS e SciELO e nas referências de artigos relevantes ao tema. Dos 107 trabalhos encontrados, cinco foram incluídos após análise dos critérios de elegibilidade e da qualidade metodológica, totalizando 422 pacientes, sendo 227 do grupo controle. Apesar das limitações reportadas, quatro dos cinco estudos incluídos indicam que a ponte de tirofiban é eficaz em reduzir eventos cardíacos adversos e segura ao não interferir no risco de eventos hemorrágicos ou sangramentos. Todavia, são necessários ensaios clínicos randomizados para evidências robustas.

Abstract Use of a tirofiban bridge is an alternative to simply withdrawing dual antiplatelet therapy prior to operating on patients at high risk of stent thrombosis and bleeding. We aimed to evaluate the efficacy and safety of this protocol in patients undergoing surgery within 12 months of a percutaneous coronary intervention involving stenting. We performed a systematic review based on searches of the PubMed, Web of Science, Cochrane, Embase, Lilacs, and Scielo databases and of the references of relevant articles on the topic. Five of the 107 studies identified were included after application of eligibility criteria and analysis of methodological quality, totaling 422 patients, 227 in control groups. Notwithstanding the limitations reported, four of the five studies included indicate that the tirofiban bridge technique is effective for reducing adverse cardiac events and is safe in terms of not interfering with the risk of hemorrhagic events or bleeding. However, randomized clinical trials are needed to provide robust evidence.

Statistical analysis for efficacy of tirofiban combined with ozagrel in the treatment of progressive cerebral infarction patients out of thrombolytic therapy time window

OBJECTIVES: To investigate the safety and efficacy of combined tirofiban-ozagrel therapy for treating progressive stroke patients out of thrombolytic therapy time window. METHODS: This prospective, double-blind, randomized controlled study included 337 patients who had experienced an acute ischemic stroke between November 2017 and December 2018. All patients were randomized into three groups: 1) the tirofiban/ozagrel group (n=113), 2) the tirofiban group (n=110), and 3) the ozagrel group (n=114). The platelet aggregation (PAG), thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen (FIB) levels in the patients from these groups were evaluated before starting treatment and then, at 24h, 7 days, and 14 days after treatment. The National Institutes of Health Stroke Scale (NIHSS) scores were evaluated before treatment and then, 24h, 1 week, 2 weeks, and 4 weeks after treatment. The Barthel Index (BI) score was used to measure safety, and the modified Rankin scale (mRS) was used to evaluate disability following 3 months of treatment. The risk factors affecting clinical outcomes were analyzed using logistic multivariate regression. RESULTS: The mean NIHSS score for all the patients was 13.17±3.13 before treatment, and no significant difference between the basic clinical parameters of the three patient groups was found. Following treatment, both PAG and FIB were significantly reduced compared with the baseline (p<0.05). The levels of PAG and FIB in the tirofiban/ozagrel group were significantly lower than those in the tirofiban and ozagrel groups at 24h and 7 days after treatment (p<0.05). The NIHSS score decreased significantly in all treatment groups (p<0.05). The tirofiban/ozagrel NIHSS scores were significantly lower than that of the tirofiban and ozagrel groups at 24h, 1 week, and 2 weeks post initiation (p<0.05 for all). There were no significant differences in the BI and mRS scores or the intracranial hemorrhage rates; further, age, sex, Trial of ORG 10172 in acute stroke treatment (TOAST) type, baseline NIHSS and 24-h NIHSS scores, baseline thrombus-related factors, and treatment methods were shown to not be independent risk factors for clinical outcomes. CONCLUSION: The combination of tirofiban and ozagrel, as well as monotherapy with either tirofiban or ozagrel, transiently improves the neural function of patients and reduces platelet aggregation and fibrinogen formation in the first 4 weeks following a stroke event; additionally, none of these treatments increased the risk for hemorrhage in these progressive stroke patients over a 3-month period.

Treatment of hemiplegic stroke warning syndrome: comparison between tirofiban and aspirin combined with clopidogrel / 国际脑血管病杂志

Objective:To investigate the clinical safety and efficacy of tirofiban in the treatment of hemiplegic stroke warning syndrome.Methods:Patients with hemiplegic stroke warning syndrome admitted to Jining First People's Hospital without receiving intravenous thrombolysis from January 2018 to May 2020 were enrolled retrospectively. Some patients were given tirofiban intravenous infusion for at least 24 h in acute phase, then received oral antiplatelet therapy (tirofiban group); some only received aspirin+ clopidogrel dual antiplatelet therapy (control group). The primary endpoint was muscle strength at the paralytic side and National Institutes of Health Stroke Scale (NIHSS) score at day 7 after onset. The secondary endpoint was the modified Rankin Scale (mRS) score at 3 months after onset, and ≤2 was defined as good clinical outcome. The safety endpoint was the bleeding events during treatment. Multivariate logistic regression analysis was used to determine the independent influencing factors of clinical outcome. Results:A total of 30 patients with hemiplegic stroke warning syndrome were enrolled, including 19 (63.3%) in the tirofiban group and 11 (36.7%) in the control group. There was no significant difference in baseline clinical data between the two groups, and no drug-related bleeding complications occurred during treatment. The muscle strength at paralytic side and NIHSS score at day 7 after onset, NIHSS score at discharge and good clinical outcome rate at 3 months in the tirofiban group were significantly better than those in the control group, and the differences were statistically significant (all P<0.05). Multivariate logistic regression analysis showed that tirofiban was an independent protective factor for good outcome after adjusting the NIHSS score at the beginning of treatment (odds ratio 0.040, 95% confidence interval 0.040-0.449; P=0.009). Conclusions:Tirofiban is safe and effective in the treatment of patients with hemiplegic stroke warning syndrome in acute phase. It can effectively block the progress of the disease, improve the outcome of patients, and will not increase the risk of bleeding.

Forced degradation studies and stability-indicating liquid chromatography method for determination of tirofiban hydrochloride and synthetic impurities / Estudo da degradação forçada e método indicativo da estabilidade por cromatografía líquida para determinação de cloridrato de tirofibana e impurezas sintéticas

SUMMARY This study aimed to develop and validate a stability-indicating liquid chromatography method for the determination of tirofiban hydrochloride and two synthetic impurities (impurity A and impurity C). The method utilizes a RP-18 column (250 mm x 4.6 mm; 5 µm) with the PDA detector for quantitation. A mixture of triethylamine 0.1% (acidified to pH 5.5 with phosphoric acid) and acetonitrile was used as the mobile phase at a flow rate of 1 mL min-1 with gradient elution. The method presented satisfactory linearity, precision, accuracy and robustness, as well as low limits of detection and quantification, which demonstrate sensitivity in the determination of tirofiban and impurities A and C. It was selective for the determination of the drug and impurities analysed, without interference of the degradation products generated under forced conditions, demonstrating the stability-indicating capacity of the proposed method. Tirofiban showed to be practically stable to oxidative (30% H2O2 for 24 h) and thermal (75 °C for 24 h) conditions, but presented degradation to UVA light and acid hydrolysis, obeying the first order kinetics for both. In this way, it can be used as a stability-indicating method in the quality control of the raw material of tirofiban hydrochloride, as well as of the finished product. The obtained results demonstrate the importance of deepening the studies in this area, to guarantee the quality of commercialized pharmaceutical products.

RESUMO Este estudo teve como objetivo desenvolver e validar método indicativo da estabilidade por cromatografía líquida para determinação de cloridrato de tirofibana e duas impurezas de síntese (impureza A e impureza C). O método utilizou coluna de fase reversa RP-18 (250 mm x 4,6 mm; 5 µm) e detector PDA para quantificação. A fase móvel foi composta por uma mistura de trietilamina 0,1% (acidificada com ácido fosfórico para pH 5,5) e acetonitrila, à vazão de 1 mL/min, no modo gradiente. O método apresentou linearidade, precisão, exatidão, robustez, bem como baixos limites de detecção e quantificação, demonstrando sensibilidade na determinação da tirofibana e impurezas A e C. O método apresentou seletividade na determinação do fármaco e das impurezas, sem interferência dos produtos de degradação gerados na degradação forçada da tirofibana, demonstrando sua capacidade indicativa de estabilidade. O fármaco apresentou-se estável a oxidação (H2O2 30% por 24 h) e a degradação térmica (75 °C por 24 h), mas degradou frente à luz UVA e hidrolise ácida, obedecendo cinética de primeira ordem para ambas. Dessa forma, pode ser utilizado como um método indicativo de estabilidade no controle de qualidade da matéria -prima do cloridrato de tirofibana, bem como no produto acabado. Os resultados obtidos demonstram a importância de aprofundar os estudos na área, com intuito de garantir a qualidade dos produtos farmacêuticos comercializados.

Rapid Health Technology Assessment of Tirofiban in the Treatment of Acute Coronary Syndrome / 中国药房

OBJECTIVE：To evaluate the benefit and risk of tirofiban in the treatment of acute coronary syndrome （ACS），and to provide evidence-based reference for clinical drug selection and decision. METHODS ：Retrieved from domestic and foreign database as PubMed ，the Cochrane Library ，CNKI and Wanfang database ，during the establishment of database to Apr. 2020，two researcher independently screened the literature based on inclusion and exclusion criteria and extracted the data. After the quality evaluation of the included literatures ，based on rapid health technology assessment ，the extracted results were classifiedly evaluated and comprehensively analyzed. RESULTS ：A total of 13 researches of systematic review/Meta-analysis and 1 research of pharmacoeconomics were included. Compared with placebo ，tirofiban could significantly reduce all-cause mortality [OR ＝0.68， 95％CI（0.54，0.86），P＝0.000 1] and the incidence of major adverse cardiac events （MACE）in patients with ACS [RR ＝0.24， 95％CI（0.14，0.40），P＜0.01]，and increased the incidence of TIMI 3 [OR＝5.73，95％CI（2.99.10.97），P＜0.01]. Tirofiban and eptifibatide had similar therapeutic efficacy in the treatment of ACS ，but tirofiban significantly increased the risk of TIMI small bleeding in patients with ACS [RR ＝0.61，95％CI（0.38，0.98），P＝0.04]. For ACS patients with non-ST elevation （NSTE-ACS）， compared with placbo ，tirofiban significantly reduced the incidence of MACE [RR ＝0.76，95％ CI（0.61，0.96），P＝0.018]，but significantly increased the risk of bleeding [OR ＝1.49，95％CI（1.12，1.98），P＝0.006]，while there was no significant difference in its effects on the all-cause mortality of NSTE-ACS patients （P＞0.05）. For STEMI patients ，compared with placebo ，tirofiban significantly reduced the all-cause mortality [RR＝0.61，95％CI（0.35，1.05），P＝0.007] and the incidence of MACE [RR ＝0.63，95％ CI（0.44，0.90），P＝0.007]. When combined with liposuction ，tirofiban also significantly reduced the incidence of MACE [RR ＝ 2.05，95％CI（1.71，2.46），P＜0.01]，and significantly increased the incidence of TIMI 3 [OR＝3.18，95％ CI（2.4，4.22），P＜ 0.01]，but there was no significant difference in its effects on bleeding risk （P＞0.05）. The included pharmacoeconomic study showed that patients treated with bivalutine could get 10.07 QALYs，patients treated with heparin combined with tirofiban could get 9.98 QALYs，and the incremental cost-effectiveness ratio bivalutine compared to the latter one was 28 575.77 yuan/QALYs，which was lower than 3 times of the per capita GDP of some cities. CONCLUSIONS ：Tirofiban has good efficacy in the treatment of ACS，but it can increase the risk of bleeding than eptifibatide and placebo. Domestic bivalirudin treating for ACS has a cost-effectiveness advantage over tirofiban combined with heparin.

Clinical efficacy of tirofiban combined with a Solitaire stent in treating acute ischemic stroke

This study explores the safety and effect of acute cerebral infarction treatment by microcatheter injection of tirofiban combined with a Solitaire AB stent and/or stent implantation. Emergency cerebral angiograms showing the responsible vascular occlusion of 120 acute cerebral infarction patients who underwent emergency endovascular thrombectomy were included in the study. These patients were randomly divided into two groups using the random number table method: treatment group (n=60) that received thrombectomy (with cerebral artery stents) combined with intracerebral injection of tirofiban and control group (n=60) that only received thrombectomy (with cerebral artery stents alone). The baseline data, cerebral angiography before and after surgery, hospitalization, and follow-up results of patients in these two groups were compared. Furthermore, the incidence of major adverse cerebrovascular events of these two groups was compared (90-day modified Rankin scale, a score of 0-2 indicates a good prognosis). The difference between baseline clinical data and brain angiography between these two groups was not statistically significant. Patients in the treatment group had a higher prevalence of thrombolysis in cerebral infarction grade 2b/3 than patients in the control group (88.3% (53/60) vs 66.7% (40/60), P=0.036). Moreover, the National Institutes of Health Stroke Scale scores 7 days after surgery and the 90-day prognosis were all better for the patients who received tirofiban (P=0.048 and P=0.024). Mechanical thrombectomy with Solitaire AB stents in combination with the injection of tirofiban through a microcatheter appears to be safe and effective for the endovascular treatment of acute ischemic stroke.

Application of tirofiban in reperfusion treatment of acute ischemic stroke / 国际脑血管病杂志

Vascular recanalization is an important treatment method for acute ischemic stroke. Antiplatelet drugs combined with intravenous thrombolysis and endovascular therapy have become the research hotspots in recent years. Platelet glycoprotein Ⅱb/Ⅲa receptor antagonist is a new class of antiplatelet drugs that work by inhibiting the last common pathway in the platelet aggregation process. Its safety and effectiveness in the treatment of acute coronary syndrome have been proven, but its application in patients with acute ischemic stroke is still in the exploratory stage. This article reviews the application of tirofiban in the treatment of acute ischemic stroke reperfusion.

The research progress for the role of platelet in sepsis and anti⁃platelet therapy / 医学研究生学报

The clinical treatment of sepsis has always been a problem. Sepsis is characterized by high morbidity, high mortality and high treatment costs.Platelets were previously thought to play a major role in hemostasis and thrombosis.In recent years, it has been found that platelets are very important in inflammation and immune regulation as well as in hemostasis and thrombosis. Antiplatelet therapy can reduce release of inflammation and immunomodulatory mediators by attenuating platelet activation, thereby alleviating the inflammatory response in sepsis. This paper reviews the mechanism of platelet involvement in sepsis and the clinical progress of antiplatelet drugs in managing sepsis.

Influence of tirofiban‐assisted PCI on serum sST2 and PTX‐3 levels in patients with acute ST‐segment elevation myocardial infarction／ / 心血管康复医学杂志

To explore therapeutic effect of tirofiban‐assisted percutaneous coronary intervention (PCI) on patients with acute ST‐segment elevation myocardial infarction (STEMI) and its influence on serum levels of soluble stromelysin 2 (sST2) and pentraxin (PTX)‐3. Methods : A total of 146 STEMI patients treated in our hospital from 2014 to 2017 were randomly and equally divided into pure PCI group and combined treatment group (received tirofi‐ ban and PCI ) , both groups received aspirin and clopidogrel for 7d after PCI .After treatment , TIMI blood flow grade , serum levels of sST2 and PTX‐3 , LVEDd and LVEF and incidence of major adverse cardiovascular events (MACE) were observed and compared between two groups .Results : After treatment , percentage of TIMI＜grade 3 in combined treatment group was significantly lower than that of pure PCI group (13. 7% vs.34. 2%, P＝0.003 ?).Compared with pure PCI group , there was significant rise in LVEF [ (54.34 ± 6.57 )% vs.(61.42 ± 7.31)%] and significant reductions in LVEDd [ (49. 35 ± 3.13) mm vs.(43.54 ± 3. 44) mm] after six months , ser‐um levels of sST2 [ (57.42 ± 8.93) μg／L vs .(35. 22 ± 8. 53) μg／L] and PTX‐3 [ (0.64 ± 0.11) μg／L vs.(0. 43 ± 0.09) μg／L] after one month in combined treatment group , P＝0. 001 all.During six‐month follow‐up , total inci‐dence rate of MACE in combined treatment group was significantly lower than that of pure PCI group (2. 7% vs. 24.7%, P＝0. 001).Conclusion : Tirofiban‐assisted PCI is beneficial for improving cardiac function , reducing ser‐um sST2 and PTX‐3 levels and incidence rate of MACE in STEMI patients after PCI , which is worth extending .24

Therapeutic effect of thrombus aspiration combined tirofiban on AMI patients undergoing PCI and its influence on cTnT level / 心血管康复医学杂志

Objective :To explore therapeutic effect of thrombus aspiration combined tirofiban on patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) and its influence on level of car— diac troponin T (cTnT).Methods : A total of 108 AMI patients treated in our ICU were randomly and equally divid—ed into pure PCI group and combined treatment group (received thrombus aspiration combined tirofiban during PCI).Therapeutic effect and serum cTnT level were compared between two groups .Results : Compared with pure PCI group ,there were significant rise in TIMI blood flow improvement rate (77.78% vs .94.44%) and ST segment regression rate (72. 22% vs.90. 74%) within 90min after PCI , P＝0. 012 ,0.013 ;on 30d after PCI ,there was sig—nificant rise in LVEF [ (46. 34 ± 0. 53 )% vs.(53.41 ± 0.32)%] ,and significant reductions in LVEDd [ (6.02 ± 0.32) cm vs.(5.34 ± 0.22) cm] and incidence rate of MACE within three months (20.37% vs.3.70%) in com—bined treatment group , P＜0. 01 all.Compared with before PCI ,there was significant reduction in serum cTnT lev—el in two groups on 3d after PCI ,and that of combined treatment group was significantly lower than that of pure PCI group [(0.19 ± 0. 05) ng／ml vs.(0. 32 ± 0.03) ng／ml] , P＝0.001. Conclusion : Thrombus aspiration combined tirofiban during PCI can significantly improve blood flow of infarct related artery and cardiac function ,relieve myo—cardial injury ,reduce incidence rate of MACE in AMI patients from severe ICU .

Therapeutic effect of PCI combined tirofiban on aged patients with ACS complicated diabetes mellitus and its safety／ / 心血管康复医学杂志

Objective :To explore therapeutic effect of percutaneous coronary intervention (PCI ) combined hydro‐chloride tirofiban on aged patients with acute coronary syndrome (ACS) complicated diabetes mellitus (DM) and its safety .Methods :A total of 218 ACS + DM patients were selected .According to randomization method ,they were divided into routine treatment group (n＝107 ,received standard PCI) and tirofiban group (n＝111 ,received tirofi‐ban injection in coronary artery based on routine treatment group ).Operation indexes ,incidence rates of hemor‐rhage during hospitalization and major adverse cardiovascular events (MACE) within six months after PCI were ob‐served and compared between two groups .Results : There was no significant difference in door‐to‐balloon time , number and length of implanted stents between two groups , P＞0.05 all.Compared with routine treatment group , there were significant rise in percentages of TIMI grade 3 blood flow (75. 70% vs.91.89%) ,MBG grade 2 ～3 (69.16% vs.85.56%) and ST segment regression ＞50% within 90min after PCI (77. 57% vs.92.79%) ,and sig‐nificant reduction in corrected TIMI frame count (CTFC)[(33. 05 ± 8.37) frames vs.(26.54 ± 5.47) frames]in tiro‐fiban group , P＜0.01 all.There was no significant difference in incidence rate of hemorrhage events during hospi‐talization between two groups , P＝0.375. Incidence rate of MACE within six months in tirofiban group was signifi‐cantly lower than that of routine treatment group ,P＝0.001 .Conclusion :Intracoronary tirofiban injection based on routine PCI can significantly improve postoperative myocardial perfusion level ,reduce incidence rate of short‐term MACE after PCI without increasing incidence rate of hemorrhage in aged ACS patients .Its safety is good .

Observation on efficacy of tirofiban in patients with ischemic progressive stroke / 中华疾病控制杂志

Objective To observe the efficacy of tirofiban in the treatment of ischemic progressive stroke. Methods 300 patients who met the diagnostic criteria of ischemic progressive stroke were divided into the control group and tirofiban group. Patients in the control group received treatment of PA2S regiment, i.e., a combination of aspirin, clopidogrel, probucol and atorvastatin. Patients in the tirofiban group received extra tirofiban on the basis of PA2S therapy. National institute of health stroke scale (NIHSS) score was evaluated on patients in both group before the therapy and 3 days, 1 month, 6 months after the therapy respectively. Results For the control group, the average NIHSS score was 11.3±4.2,11.5±4.4,8.8±4.1,6.1±4.1 before therapy and at 3 days, 1 month, 6 months after the therapy. And for the tirofiban group, the average NIHSS score was 11.4±3.9, 10.8±3.6, 7.4±3.2, 4.4±3.0 at the corresponding period respectively. There were statistical differences between the two groups in the period of 1 month and 6 months after treatment with P<0.001. Conclusions Tirofiban hydrochloride can improve the degree of neurological deficit and outcome in patients with ischemic progressive stroke.

Effects of Rosuvastatin Combined with Tirofiban on Serum Inflammatory Factors and Renal Function in Acute Coronary Syndrome Patients with Diabetes after PCI / 中国药房

OBJECTIVE: To investigate the effects of rosuvastatin combined with tirofiban on serum inflammatory factors and renal function in acute coronary syndrome patients with diabetes after percutaneous coronary intervention (PCI).METHODS: A total of 120 acute coronary syndrome patients with diabetes receiving PCI selected from cardiology department of our hospital during Apr. 2014-Mar. 2015 were divided into control group and observation group according to random number table, with 60 cases in each group. Except for routine treatment, control group was given Rosuvastatin calcium tablets orally after surgery (10 mg each day, for consecutive 7 d); observation group was given Rosuvastatin calcium tablets orally before and after surgery (20 mg before surgery; 10 mg each day after surgery, for consecutive 7 d), and then given Tirohydrochloric acid sodium chloride injection during surgery [10 μg/kg intravenously, 0. 15 μg/(kg· min) with intravenous pump for 36 h]. Clinical efficacies of 2 groups were compared. The changes of serum inflammatory factors (TNF-α, IL-6, IL-10) and renal function indexes (Scr, CysC, eGFR), the incidence of radiographic contrast nephropathy were compared before surgery and 24, 72 h after surgery. The occurrence of cardiovascular events was followed up for one year. RESULTS: There were no statistical significance in baseline information between 2 groups before treatment (P>0. 05). The number of complete remission case and total response rate in observation group were increased significantly higher than control group (P<0. 05), while number of invalid cases was significantly lower than control group (P<0. 05). Compared with before surgery, the levels of serum inflammation factor in 2 groups were decreased significantly 24, 72 h after surgery, while the levels of Scr and CysC were increased significantly in control group 24, 72 h after surgery and in observation group 24 h after surgery; the level of eGFR was decreased significantly, while the level of CysC was increased significantly in observation group 72 h after surgery, with statistical significance (P<0. 05). The improvement of serum inflammation factors and renal function indexes in observation group were more significant than control group (P<0. 05); the incidence of radiographic contrast nephropathy was significantly lower than control group (P<0. 05). The incidence of 1-year angina pectoris and total incidence of cardiovascular events were significantly lower than control group (P< 0. 05). CONCLUSIONS: Rosuvastatin combined with tirofiban can promote the recovery of renal function in acute coronary syndrome patients with diabetes after PCI, reduce the levels of serum inflammatory factors and decrease the incidence of radiographic contrast nephropathy and post-treatment cardiac events. Its effects are different from rosuvastatin alone.

Therapeutic Efficacy of Ezetimibe Combined with Tirofiban in the Treatment of Acute Coronary Syndrome Patients and Its Influence on the Content of Ischemia Modified Albumin / 中国药房

OBJECTIVE:To investigate therapeutic efficacy of ezetimibe combined with tirofiban in the treatment of acute coronary syndrome patients and its influence on the content of ischemia modified albumin (IMA) in peripheral blood.METHODS:A total of 82 patients with acute coronary syndrome in our hospital from Jan.2016 to Jan.2017 were divided into observe group and control group according to random number table,with 41 cases in each groups.All patients were given general treatment containing statins,glyceryl trinitrate and so on.Control group was additionally given Ezetimibe tablet 10 mg orally once a day.Observation group was additionally given Tirofiban hydrochloride sodium chloride injection 5 mg intravenously once a day,on the basis of control group,for consecutive 15 d.Clinical efficacies of 2 groups were evaluated.The dose of glyceryl trinitrate,duration and frequency of angina pectoris attack,left ventricular function indexes (SV,LVDD,CO,LVEF) were compared before treatment and after last medication.The contents of IMA in peripheral blood were detected before treatment and 3,6,9,12,15 h after the first day medication.ADR of the 2 groups were observed closely during the treatment.RESULTS:The total response rate of observation group was 92.7％,which was significantly higher than 72.3％ of control group (P＜0.05).Compared with before treatment,dose of glyceryl trinitrate and the content of IMA in 2 groups were decreased significantly after last medication,duration and frequency of angina pectoris attack were shortened significantly;the levels of SV,CO and LVEF were increased significantly while the level of LVDD was decrease significantly;the effect of observation group was significantly better than that of control group,with statistical significance (P＜0.05).No severe ADR was found in all patients during the treatment.CONCLUSIONS:Based on general treatment of glyceryl trinitrate therapeutic efficacy of ezetimibe combined with tirofiban is better than that of ezetimibe alone in the treatment acute coronary syndrome patients,and can decrease the content of IMA in peripheral blood more quickly.