Search Results (16)

Background/Objectives: Acute carotid tandem lesions (TLs), defined by concurrent cervical internal carotid artery (ICA) stenosis or occlusion and intracranial large vessel occlusion, occur in 10–20% of patients undergoing mechanical thrombectomy (MT) for acute ischemic stroke (AIS). Optimal periprocedural antiplatelet management during emergent carotid artery stenting (eCAS) remains uncertain, particularly regarding the balance between preventing stent thrombosis and avoiding hemorrhagic complications. Methods: A narrative review was conducted using PubMed and Scopus (until 6 March 2026) to identify English-language studies evaluating antiplatelet therapies during eCAS for TLs. We included seven real-world studies and registry analyses. Data on study design, patient characteristics, procedural strategies, angiographic results, functional outcomes, and safety metrics were extracted. Results: No randomized controlled trials (RCTs) were identified. The available evidence is derived exclusively from observational studies. Across these cohorts, glycoprotein IIb/IIIa inhibitors (GPIs), particularly tirofiban, were generally associated with lower rates of in-stent thrombosis and higher reperfusion success, with symptomatic intracranial hemorrhage (sICH) rates that appeared comparable to or lower than those reported with acetylsalicylic acid (ASA). Cangrelor, an intravenous (IV) P2Y₁₂ inhibitor, was associated with improved stent patency and increased likelihood of complete reperfusion, although reported effects on clinical outcomes were inconsistent when compared with GPIs or ASA. Aside from abciximab, potent IV antiplatelet agents did not consistently show an increased sICH signal. Oral dual antiplatelet therapy was also associated with improved technical outcomes without a clear excess in bleeding complications. Conclusions: Current real-world observational data suggest that rapid-acting IV antiplatelet agents—particularly GPIs and, increasingly, cangrelor—may represent feasible periprocedural options during eCAS for TLs, with potential benefits for technical success and no consistent evidence of increased hemorrhagic risk. However, interpretation is limited by study heterogeneity and non-randomized designs. The absence of RCTs highlights the need for prospective comparative studies and standardized periprocedural antiplatelet protocols. Full article

Background and Objectives: Inflammation contributes to plaque rupture and thrombosis in ST-elevation myocardial infarction (STEMI). The Aggregate Index of Systemic Inflammation (AISI) is a novel biomarker that reflects innate immune and thrombotic activation. Due to the connection between inflammation and thrombosis, higher AISI values could indicate a greater thrombus burden and the necessity of glycoprotein IIb/IIIa inhibitors. The aim of this study was to assess the relationship between AISI and tirofiban use during primary percutaneous coronary intervention (PCI) in STEMI patients. Materials and Methods: This retrospective study included 2624 STEMI patients who underwent primary PCI at a tertiary heart center between 2019 and 2024. Patients with pre-hospital fibrinolysis, missing laboratory data, or rescue PCI were excluded. AISI was calculated as (neutrophil × monocyte × platelet)/lymphocyte. The primary outcome was tirofiban use during PCI. Univariate and multivariable logistic regression analyses were performed to identify independent predictors, and receiver operating characteristic (ROC) curve analysis was used to evaluate AISI performance. Statistical significance was defined as p < 0.05. Results: Among the 2624 patients with STEMI undergoing primary PCI, tirofiban was administered in 23.5% of cases. Patients receiving tirofiban had significantly higher AISI values (p < 0.001). ROC analysis demonstrated that AISI predicted tirofiban use with a modest discriminative performance (AUC = 0.566; 95% CI 0.536–0.596; p < 0.001). In multivariable logistic regression, younger age (OR 0.98; p < 0.001), higher AISI (per 100-unit increase; OR 1.01; p = 0.037), and lower LVEF (OR 0.98; p < 0.001) independently predicted tirofiban use, whereas admission glucose showed only borderline significance (p = 0.089). Conclusions: Elevated AISI was independently associated with tirofiban use during primary PCI, indicating that systemic inflammatory status parallels intraprocedural decision-making in STEMI. Although its discriminative performance was modest, AISI reflects systemic inflammatory–thrombotic activation in this clinical setting. Full article

Background/Objectives: Patients that undergo percutaneous coronary intervention (PCI) require effective antiplatelet therapies to minimize the risk of thrombotic cardiovascular events. Oral P2Y12 inhibitors are often utilized, however co-administered opioids may lead to gastric absorption issues in these patients, affecting the efficacy of oral inhibitors. Cangrelor is an intravenous, direct-acting, reversible P2Y12 inhibitor that could be explored as a potential treatment option for patients with gastric absorption issues during ST-elevation myocardial infarction. The objective was to estimate the UK budget impact of introducing cangrelor for ST-elevation myocardial infarction (STEMI) patients with gastric absorption issues undergoing PCI. Methods: A budget impact model was developed to calculate the impact of introducing cangrelor to treat STEMI patients with gastric absorption issues undergoing PCI, to the UK National Health Service and personal social services, over 5 years. Oral P2Y12 inhibitors (clopidogrel, prasugrel, and ticagrelor), glycoprotein IIb/IIIa inhibitors (eptifibatide and tirofiban), and aspirin and heparin alone were included as base case comparators. Cangrelor uptake ranged from 10% to 30% in years 1–5. The cangrelor-eligible population was estimated at 10,903 patients per year. Results: Over 5 years, cangrelor leads to a small cost saving (0.29%), varying from −GBP 261,989 in year 1 to GBP 174,778 in year 5. The introduction of cangrelor is estimated to lead to 314 fewer hospital days and 190 clinical events avoided over 5 years. Conclusions: Introducing cangrelor to STEMI patients with gastric absorption issues undergoing PCI in the UK is estimated to generate a small cost saving and reduced length of stay for some patients. Full article

The currently available point-of-care hemostasis tests are burdened by criticisms concerning the use of different activators and inhibitors and the lack of dynamic flow. These operating conditions may constitute an impediment to the determination of the patient’s hemostatic condition. Hence, the diffusion of these tests in clinical practice is still limited to specific scenarios. In this work, we present a new method for analyzing the patient’s global hemostasis based on the visualization of the main components of the coagulation process and its computerized quantitative image analysis. The automated “Smart Clot” point-of-care system presents a micro-fluidic chamber in which whole blood flows, without the addition of any activator or inhibitor. In this micro-channel, platelet adhesion, activation and aggregation to the type I collagen-coated surface take place (primary hemostasis), leading to the production of endogenous thrombin on the surface of platelet aggregates and the consequent fibrin mesh and thrombus formation (secondary hemostasis). These observations are verified by inhibiting primary hemostasis with the antiplatelet drugs Indomethacin (−70% on platelet aggregation, −60% on fibrin(ogen) formation) and Tirofiban (complete inhibition of platelet aggregation and fibrin(ogen) formation) and secondary hemostasis with the antithrombin drugs Heparin (−70% on platelet aggregation, −80% on fibrin(ogen) formation) and Lepirudin (−80% on platelet aggregation, −90% on fibrin(ogen) formation). Smart Clot, through a single test, provides quantitative results concerning platelet aggregation and fibrin formation and is suitable for undergoing comparative studies with other coagulation point-of-care devices. Full article

Natural monoterpenes and their derivatives are widely considered the effective ingredients for the design and production of novel biologically active compounds. In this study, by using the molecular docking technique, we examined the effects of two series of “sulfide-sulfoxide-sulfone” thioterpenoids containing different (e.g., bornane and pinane) monoterpene skeletons on the platelet’s aggregation. Our data revealed that all the synthesized compounds exhibit inhibitory activities on platelet aggregation. For example, compound 1 effectively inhibited platelet activation and demonstrated direct binding with CD61 integrin, a well-known platelet GPIIb-IIIa receptor on platelets. We further examined the antiaggregant activity of the most active compound, 1, in vivo and compared its activity with that of acetylsalicylic acid and an oral GPIIb-IIIa blocker, orbofiban. We found that compound 1 demonstrates antiaggregant activity in rats when administered per os and its activity was comparable with that of acetylsalicylic acid and orbofiban. Moreover, similarly, tirofiban, a well-known GPIIb-IIIa blocker, compound 1, effectively decreased the expression of P-selectin to the values similar to those of the intact platelets. Collectively, here, we show, for the first time, the potent antiaggregant activity of compound 1 both in vitro and in vivo due to its ability to bind with the GPIIb-IIIa receptor on platelets. Full article

The use of periprocedural dual antiplatelet therapy (DAPT) has significantly evolved along with innovations in the endovascular management of intracranial aneurysms. Historically, aspirin and clopidogrel have been the most commonly employed regimen due to its safety and efficacy. However, recent studies highlight the importance of tailoring DAPT regimens to individual patient characteristics which may affect clopidogrel metabolism, such as genetic polymorphisms. In the present report, a systematic review of the literature was performed to determine optimal antiplatelet use with flow diverting stents, intracranial stents, intrasaccular devices, and stent-assisted coiling. Studies were analyzed for the number of aneurysms treated, DAPT regimen, and any thromboembolic complications. Based on inclusion criteria, 368 studies were selected, which revealed the increasing popularity of alternative DAPT regimens with the aforementioned devices. Thromboembolic or hemorrhagic complications associated with antiplatelet medications were similar across all medications. DAPT with ticagrelor, tirofiban, or prasugrel are effective and safe alternatives to clopidogrel and do not require enzymatic activation. Further clinical trials are needed to evaluate different antiplatelet regimens with various devices to establish highest-level evidence-based guidelines and recommendations. Full article

Heparin-induced thrombocytopenia (HIT) is a major issue in cardiac surgery requiring cardiopulmonary bypass (CPB). HIT represents a severe adverse drug reaction after heparin administration. It consists of immune-mediated thrombocytopenia paradoxically leading to thrombotic events. Detection of antibodies against platelets factor 4/heparin (anti-PF4/H) and aggregation of platelets in the presence of heparin in functional in vitro tests confirm the diagnosis. Patients suffering from HIT and requiring cardiac surgery are at high risk of lethal complications and present specific challenges. Four distinct phases are described in the usual HIT timeline, and the anticoagulation strategy chosen for CPB depends on the phase in which the patient is categorized. In this sense, we developed an institutional protocol covering each phase. It consisted of the use of a non-heparin anticoagulant such as bivalirudin, or the association of unfractionated heparin (UFH) with a potent antiplatelet drug such as tirofiban or cangrelor. Temporary reduction of anti-PF4 with intravenous immunoglobulins (IvIg) has recently been described as a complementary strategy. In this article, we briefly described the pathophysiology of HIT and focused on the various strategies that can be applied to safely manage CPB in these patients. Full article

Tirofiban has recently shown encouraging efficacy and safety among acute ischemic stroke (AIS) patients with mechanical thrombectomy (MT). However, the benefits of tirofiban varied among studies depending on the patient’s condition, which was often not well analyzed. This study aimed to identify the characteristics of patients who may obtain the largest benefits from tirofiban. The efficacy endpoint was a favorable outcome defined as a modified Rankin Scale (mRS) score of 0~2 at 90 days. The safety endpoints were intracranial hemorrhage (ICH), symptomatic intracranial hemorrhage (sICH) and mortality at 90 days. Adjusted logistic regression analysis and subgroup analyses were utilized to investigate the factors associated with tirofiban and the outcome. All of 285 patients fit the inclusion criteria. Tirofiban was associated with a higher rate of favorable outcome (aOR 2.033, 95% CI, 1.002~4.123, p = 0.043) but not with an increased risk of ICH, sICH or mortality (p > 0.05). Moreover, subgroup analyses revealed that tirofiban was associated with favorable outcomes in patients with NIHSS > 14 (aOR 2.778, 95% CI 1.056~7.356, p = 0.038) but not in patients with NIHSS ≤ 14 (aOR 1.719, 95% CI 0.646~4.578, p = 0.278). No significant heterogeneity was found in the effect of tirofiban across the subgroups of age, sex, ASPECTS, time from onset to puncture, use of t-PA or stroke etiology (p for interaction > 0.05). The administration of tirofiban was associated with favorable outcomes in severe ischemic stroke patients, and further studies are needed to confirm this finding. Full article

Local tirofiban infusion has been reported as a rescue strategy for intracranial atherosclerotic stenosis (ICAS)-related stroke. However, the long-term outcomes of local tirofiban infusion during endovascular reperfusion therapy (ERT) for ICAS-related stroke are still uncertain. This study aimed to investigate the long-term outcomes of local tirofiban infusion during ERT. We retrospectively analyzed acute patients with ICAS-related stroke who were treated with local tirofiban as a rescue strategy during ERT. The primary outcomes were ischemic stroke, transient ischemic stroke (TIA), and stroke-related death within 30 days. Secondary outcomes included ischemic stroke and TIA beyond 30 days and up to 2 years after ERT in the corresponding treated vessel, symptomatic brain hemorrhage, any stroke, and non-stroke-related death. During a median follow-up of 24.0 months, 12 patients developed an ischemic stroke and TIA (4 within 30 days and 8 afterward). The 1-year risk of stroke and TIA was 9.2% (95% confidence interval, 8.0–18.6%). This study demonstrates that 1-year outcomes of local tirofiban infusion were comparable to the results of intracranial stenting in patients with symptomatic ICAS. Local tirofiban infusion for ICAS-related stroke may be a feasible rescue strategy that can have a bridging role until the maximum effect of antiplatelet agents is achieved. Full article

Patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) may demonstrate distal microvascular embolization of thrombotic materials. We retrospectively examined 20 cases displaying extensive thrombus in the infarct-related artery (IRA), treated either with a two-step procedure, with interim tirofiban infusion, or immediate stent implantation. Distal embolization tended to be more common in the latter strategy, but, overall, the outcome was comparable. Thus, a two-staged procedure may be considered in selected cases of primary PCI associated with high thrombus burden. Full article

Drug-induced immune thrombocytopenia (DITP) is a life-threatening clinical syndrome that is under-recognized and difficult to diagnose. Many drugs can cause immune-mediated thrombocytopenia, but the most commonly implicated are abciximab, carbamazepine, ceftriaxone, eptifibatide, heparin, ibuprofen, mirtazapine, oxaliplatin, penicillin, quinine, quinidine, rifampicin, suramin, tirofiban, trimethoprim-sulfamethoxazole, and vancomycin. Several different mechanisms have been identified in typical DITP, which is most commonly characterized by severe thrombocytopenia due to clearance and/or destruction of platelets sensitized by a drug-dependent antibody. Patients with typical DITP usually bleed when symptomatic, and biological confirmation of the diagnosis is often difficult because detection of drug-dependent antibodies (DDabs) in the patient’s serum or plasma is frequently not possible. This is in contrast to heparin-induced thrombocytopenia (HIT), which is a particular DITP caused in most cases by heparin-dependent antibodies specific for platelet factor 4, which can strongly activate platelets in vitro and in vivo, explaining why affected patients usually have thrombotic complications but do not bleed. In addition, laboratory tests are readily available to diagnose HIT, unlike the methods used to detect DDabs associated with other DITP that are mostly reserved for laboratories specialized in platelet immunology. Full article

Animal venoms are used as defense mechanisms or to immobilize and digest prey. In fact, venoms are complex mixtures of enzymatic and non-enzymatic components with specific pathophysiological functions. Peptide toxins isolated from animal venoms target mainly ion channels, membrane receptors and components of the hemostatic system with high selectivity and affinity. The present review shows an up-to-date survey on the pharmacology of snake-venom bioactive components and evaluates their therapeutic perspectives against a wide range of pathophysiological conditions. Snake venoms have also been used as medical tools for thousands of years especially in tradition Chinese medicine. Consequently, snake venoms can be considered as mini-drug libraries in which each drug is pharmacologically active. However, less than 0.01% of these toxins have been identified and characterized. For instance, Captopril^® (Enalapril), Integrilin^® (Eptifibatide) and Aggrastat^® (Tirofiban) are drugs based on snake venoms, which have been approved by the FDA. In addition to these approved drugs, many other snake venom components are now involved in preclinical or clinical trials for a variety of therapeutic applications. These examples show that snake venoms can be a valuable source of new principle components in drug discovery. Full article

Snake venoms are attractive natural sources for drug discovery and development, with a number of substances either in clinical use or in research and development. These drugs were developed based on RGD-containing snake venom disintegrins, which efficiently antagonize fibrinogen activation of αIIbβ3 integrin (glycoprotein GP IIb/IIIa). Typical examples of anti-platelet drugs found in clinics are Integrilin (Eptifibatide), a heptapeptide derived from Barbourin, a protein found in the venom of the American Southeastern pygmy rattlesnake and Aggrastat (Tirofiban), a small molecule based on the structure of Echistatin, and a protein found in the venom of the saw-scaled viper. Using a similar drug discovery approach, linear and cyclic peptides containing the sequence K(R)TS derived from VP12, a C-type lectin protein found in the venom of Israeli viper venom, were used as a template to synthesize Vipegitide, a novel peptidomimetic antagonist of α2β1 integrin, with anti-platelet activity. This review focus on drug discovery of these anti-platelet agents, their indications for clinical use in acute coronary syndromes and percutaneous coronary intervention based on several clinical trials, as well as their adverse effects. Full article

Integrin α_IIbβ₃ plays a pivotal role in platelet aggregation. Three α_IIbβ₃ antagonists have been approved by the Food and Drug Administration (FDA) for the treatment of cardiovascular diseases. Unfortunately, all of these three drugs can cause the side effect of severe bleeding. Therefore, developing a new α_IIbβ₃ antagonist with low bleeding was needed. In the present study, we screened compounds by using a fibrinogen/integrin α_IIbβ₃ enzyme-linked immunosorbent assay (ELISA), and a novel α_IIbβ₃ antagonist ANTP266 was attained. The antithrombotic effects of ANTP266 were estimated by using two animal models, the bleeding risk was estimated by using a mice tail cutting assay, and the plasma half-life time was tested by LC-MS/MS. The results showed that ANTP266 potently decreased thrombosis formation, while not prolonging bleeding time at its effective dosage. The bleeding of ANTP266 reduced rapidly as time went on from 5 to 60 min, but tirofiban produced high bleeding continuously. The plasma half-life of ANTP266 in rats was 10.8 min. Taken together, ANTP266 is an effective antithrombotic agent with a low bleeding risk. The shorter bleeding time benefits from its short plasma half-life. ANTP266 could be a candidate for developing the α_IIbβ₃ antagonist of rapid elimination for a patient undergoing percutaneous coronary intervention. Full article

Stroke patients can recover upon intravenous thrombolysis but remain impaired in lacking recanalization. We sought to investigate the clinical effect of systemic thrombolysis with an intravenous bolus of 20 mg recombinant tissue plasminogen activator (rtPA) and an infusion of body-weight adjusted tirofiban for 48 hours in acute stroke. This prospective, open label study, included 192 patients (68±13 years, 50% males) treated between 1 January 2005 and 31 December 2007. The neurological deficit was assessed with the National Institutes of Health stroke scale (NIHSS). Follow-up was performed using a telephone interview of modified Rankin Scale (mRS) and Barthel index. The site of cerebral artery occlusion was determined by computed tomography or magnetic resonance angiography. Data were analyzed by descriptive statistics and multiple regression analyses. Eighty-one percent of the patients had an infarct in the middle cerebral artery (MCA) territory and were severely affected with a median NIHSS of 10. During treatment on the Stroke Unit the patients improved (P<0.0001) except for patients who deceased due to malignant infarction (n=10) or cerebral haemorrhage (n=6); 18 percent deceased within 100 days which was predicted by older age (76 + 10 years, P<0.05) and more severe affection on admission (P<0.0001). Also, these patients more frequently had atrial fibrillation (P<0.03) than the surviving patients. The surviving patients had more frequently distal MCA occlusions and improved further (P<0.0001). At follow-up 48% of the patients had a mRS of 0 and 1. Similarly to intravenous thrombolysis with body-weight adjusted rtPA, poor prognosis was predicted by higher age, more severe neurological deficit at stroke admission, and a proximal MCA occlusion. Half of the surviving patients improved to no or minimal impairment. Full article