Combined Approach to Eptifibatide and Thrombectomy in Acute Ischemic Stroke Because of Large Vessel Occlusion: A Matched-Control Analysis.

BACKGROUND: In patients undergoing mechanical thrombectomy (MT), adjunctive antithrombotic might improve angiographic reperfusion, reduce the risk of distal emboli and reocclusion but possibly expose patients to a higher intracranial hemorrhage risk. This study evaluated the safety and efficacy of combined MT plus eptifibatide for acute ischemic stroke. METHODS: This was a propensity-matched analysis of data from 2 prospective trials in Chinese populations: the ANGEL-ACT trial (Endovascular Treatment Key Technique and Emergency Workflow Improvement of Acute Ischemic Stroke) in 111 hospitals between November 2017 and March 2019, and the EPOCH trial (Eptifibatide in Endovascular Treatment of Acute Ischemic Stroke) in 15 hospitals between April 2019 and March 2020. The primary efficacy outcome was good outcome (modified Rankin Scale score 0-2) at 3 months. Secondary efficacy outcomes included the distribution of 3-month modified Rankin Scale scores and poor outcome (modified Rankin Scale score 5-6) and successful recanalization. The safety outcomes included any intracranial hemorrhage, symptomatic intracranial hemorrhage, and 3-month mortality. Mixed-effects logistic regression models were used to account for within-hospital clustering in adjusted analyses. RESULTS: Eighty-one combination arm EPOCH subjects were matched with 81 ANGEL-ACT noneptifibatide patients. Compared with the no eptifibatide group, the eptifibatide group had significantly higher rates of successful recanalization (91.3% versus 81.5%; P=0.043) and 3-month good outcomes (53.1% versus 33.3%; P=0.016). No significant difference was found in the remaining outcome measures between the 2 groups. All outcome measures of propensity score matching were consistent with mixed-effects logistic regression models in the total population. CONCLUSIONS: This matched-control study demonstrated that MT combined with eptifibatide did not raise major safety concerns and showed a trend of better efficacy outcomes compared with MT alone. Overall, eptifibatide shows potential as a periprocedural adjunctive antithrombotic therapy when combined with MT. Further randomized controlled trials of MT plus eptifibatide should be prioritized. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03844594 (EPOCH), NCT03370939 (ANGEL-ACT).

Efficacy and safety of a bridging strategy that uses intravenous platelet glycoprotein receptor inhibitors for patients undergoing surgery after coronary stent implantation: a meta-analysis.

BACKGROUND: Current guidelines indicate we can consider a bridging strategy that uses intravenous, reversible glycoprotein inhibitors for patients that required surgery following recent stent implantation. However, no strong clinical evidence exists that demonstrates the efficacy and safety of this treatment. Therefore, in this study, the efficacy and safety of a bridging strategy that uses intravenous platelet glycoprotein receptor inhibitors will be evaluated. METHODS: A meta-analysis was performed on preoperative bridging studies in patients undergoing coronary stent surgery. The primary outcome was the success rate of no major adverse cardiovascular events (MACE). The secondary outcomes were the success rate of no reoperations to stop bleeding. RESULTS: A total of 10 studies that included 382 patients were used in this meta-analysis. For the primary endpoint, the success rate was 97.7% (95% CI 94.4-98.0%) for glycoprotein IIb/IIIa inhibitors, 98.8% (95% CI 96.0-100%) for tirofiban (6 studies) and 95.8% (95% CI 90.4-99.4%) for eptifibatide (4 studies). For secondary endpoints, the success rate was 98.0% (95% CI 94.8-99.9%) for glycoprotein IIb/IIIa inhibitors, 99.7% (95% CI 97.1-100%) for tirofiban (5 studies), and 95.3% (95% CI 88.5-99.4%) for eptifibatide (4 studies). CONCLUSION: The results of this study showed that the use of intravenous platelet glycoprotein IIb/IIIa inhibitors as a bridging strategy might be safe and effective for patients undergoing coronary stent implantation that require surgery soon after.

Efficacy outcomes and safety measures of intravenous tirofiban or eptifibatide for patients with acute ischemic stroke: a systematic review and meta-analysis of prospective studies.

To review the literature for randomized control trials (RCTs) and prospective cohort studies investigating the safety and efficacy of tirofiban and eptifibatide in patients with acute ischemic stroke (AIS). PubMed, Embase, and the Cochrane library were searched for available papers published up to September 2021. The efficacy was evaluated based on the 3-month favorable outcome [modified Rankin scale (mRS) = 0-1], functional outcome (mRS = 0-2), and the last available National Institutes of Health Stroke Scale (NIHSS) score measured in each study. Twelve studies (two RCTs and 10 prospective cohorts) and 2926 patients were included. Treatment with tirofiban or eptifibatide had no effects on the favorable outcome (RR = 1.09, 95% CI 0.89-1.35, P = 0.411), functional outcome (RR = 1.12, 95% CI 0.98-1.28, P = 0.010), and last available NIHSS (WMD = - 2.32, 95% CI - 5.14 to 0.50, P = 0.106), but might increase mortality (RR = 0.84, 95% CI 0.71-0.99, P = 0.121). The sensitivity analyses showed that the meta-analyses were robust. There was no significant publication bias. Tirofiban did not increase the risk of ICH (P = 0. 423) and sICH (P = 0. 990) but increased the risk of fatal ICH (RR = 3.59, 95% CI 1.62-7.96, P = 0.002). Thrombolysis/thrombectomy did not influence any of the outcomes. Adding tirofiban or eptifibatide to thrombolysis/thrombectomy was not significantly associated with a favorable outcome (mRS = 0-1) nor functional outcome (mRS = 0-2) in patients with AIS at 3 months, but might be associated with mortality, possibly due to fatal ICH. The NIHSS was also not significantly different between the intervention and control groups after treatments.

Eptifibatide bridging therapy for staged carotid artery stenting and cardiac surgery: Safety and feasibility.

BACKGROUND: Prophylactic carotid artery stenting (CAS) is an effective strategy to reduce perioperative stroke in patients with severe carotid stenosis who require cardiothoracic surgery (CTS). Staging both procedures (CAS-CTS) during a single hospitalization presents conflicting demands for antiplatelet therapy and the optimal pharmacologic strategy between procedures is not established. The purpose of this study is to present our initial experience with a "bridging" protocol for staged CAS-CTS. METHODS: A retrospective review of staged CAS-CTS procedures at a single referral center was performed. All patients had multivessel coronary and/or valvular disease and severe carotid stenosis (>70%). Patients not previously on aspirin were also started on aspirin prior to surgery, followed by eptifibatide during CAS (intraprocedural bolus followed by post-procedural infusion which was continued until the morning of surgery). Pre- and perioperative (30 days) neurologic morbidity and mortality was the primary endpoint. RESULTS: 11 CAS procedures were performed in 10 patients using the protocol. The median duration of eptifibatide bridge therapy was 36 h (range 24-288 h). There was one minor bleeding complication (1/11, 9.1%) and no major bleeding complications during the bridging and post-operative period. There was one post-operative, non-neurologic death and zero perioperative ischemic strokes. CONCLUSIONS: For patients undergoing staged CAS-CTS, Eptifibatide bridging therapy is a viable temporary antiplatelet strategy with a favorable safety profile. This strategy enables a flexible range of time-intervals between procedures.

Influence of integrins on thrombus formation: a road leading to the unravelling of DVT.

Integrins are a group of transmembrane glycoprotein receptors that are responsible for platelet activation through bidirectional signalling. These receptors have left their footprints in various cellular events and have intrigued many groups of scientists that have led to some significant discoveries. A lot of the recent understanding of haemostasis has been possible due to the integrins filling the gaps in between several cellular mechanism. Apart from this, other important functions carried out by integrins are growth and maturation of cardiomyocytes, mechano-transduction, and interaction with actin cytoskeleton. The signalling cascade for integrin activation involves certain intracellular interacting proteins, which initiates the step-by-step activation procedure through 'inside-out' signalling. The signalling cascade gets activated through 'outside-in' signalling with the involvement of agonists such as ADP, Fibronectin, Vitronectin, and so on. This is a crucial step for the downstream processes of platelet spreading, followed by aggregation, clot progression and finally thrombus formation. Researchers throughout the world have shown direct relation of integrins with CVD and cardiac remodelling. The present review aims to summarize the information available so far on the involvement of integrins in thrombosis and its relationship to DVT. This information could be a bedrock of hidden answers to several questions on pathogenesis of deep vein thrombosis.

Anti-thrombotic effects mediated by dihydromyricetin involve both platelet inhibition and endothelial protection.

Classical antithrombotics and antiplatelets are associated with high frequencies of bleeding complications or treatment failure when used as single agents. The platelet-independent fibrin generation by activated endothelium highlights the importance of vascular protection in addition to platelet inhibition in thrombosis prevention. Dihydromyricetin (DHM), the most abundant flavonoid in Ampelopsis grossedentata, has unique vasoprotective effects. This study aims to characterize the antithrombotic potential of DHM. The effects of DHM on the activation of platelets and endothelial cells were evaluated in vitro. Calcium mobilization and activation of mitogen-activated protein kinases (MAPKs) were examined as the potential targets of DHM based on molecular docking analysis. The in vivo effects of DHM were determined in FeCl3-injured carotid arteries and laser-injured cremasteric arterioles. The results showed that DHM suppressed a range of platelet responses including aggregation, secretion, adhesion, spreading and integrin activation, and inhibited exocytosis, phosphatidylserine exposure and tissue factor expression in activated endothelial cells. Mechanistically, DHM attenuated thrombin-induced calcium mobilization and phosphorylation of ERK1/2 and p38 both in platelets and endothelial cells. Intravenous treatment with DHM delayed FeCl3-induced carotid arterial thrombosis. Furthermore, DHM treatment inhibited both platelet accumulation and fibrin generation in the presence or absence of eptifibatide in the laser injury-induced thrombosis model, without prolonging ex vivo plasma coagulation or tail bleeding time. DHM represents a novel antithrombotic agent whose effects involve both inhibition of platelet activation and reduction of fibrin generation as a result of endothelial protection.

Perioperative Bridging With Glycoprotein IIb/IIIa Inhibitors Versus Cangrelor: Balancing Efficacy and Safety.

OBJECTIVE: To review the efficacy and safety of perioperative administration of intravenous (IV) antiplatelet agents as a substitute for oral P2Y12 inhibitors and to provide clinicians guidance on optimal and cost-effective use of these medications. DATA SOURCES: A MEDLINE literature search (1950 to November 2018) was performed using the key search terms abciximab, bridging, cangrelor, cardiac surgery, coronary artery bypass surgery, eptifibatide, intravenous antiplatelet agent, and tirofiban. Additional references were identified from a review of literature citations. STUDY SELECTION AND DATA EXTRACTION: In all, 18 original research reports and case reports/series were included in the review. DATA SYNTHESIS: Prevention of postoperative bleeding is critical to decrease morbidity and mortality after cardiac surgery. IV antiplatelet medications have short half-lives and are frequently used to substitute for oral P2Y12 inhibitors to allow platelet function recovery before procedures. Functional recovery of platelets is delayed after abciximab discontinuation and increases postoperative bleeding risk. Eptifibatide and tirofiban have similar pharmacokinetic/pharmacodynamic properties and comparable efficacy and safety in the setting of perioperative bridging. Cangrelor may be considered in patients with renal insufficiency as decreased clearance of eptifibatide or tirofiban may increase the risk of postoperative bleeding. Relevance to Patient Care and Clinical Practice: Comparative studies of IV antiplatelet medications have not been published. Appropriate use of IV antiplatelet medications can prevent perioperative ischemic events and bleeding. CONCLUSIONS: Eptifibatide, tirofiban, and cangrelor are preferred over abciximab as a perioperative bridge. The choice of agent should be tailored to clinical characteristics of the patient and institutional acquisition costs.

Co-administration of iloprost and eptifibatide in septic shock (CO-ILEPSS)-a randomised, controlled, double-blind investigator-initiated trial investigating safety and efficacy.

BACKGROUND: Part of the pathophysiology in septic shock is a progressive activation of the endothelium and platelets leading to widespread microvascular injury with capillary leakage, microthrombi and consumption coagulopathy. Modulating the inflammatory response of endothelium and thrombocytes might attenuate this vicious cycle and improve outcome. METHOD: The CO-ILEPSS trial was a randomised, placebo-controlled, double-blind, pilot trial. Patients admitted to the intensive care unit with septic shock were randomised and allocated in a 2:1 ratio to active treatment with dual therapy of iloprost 1 ng/kg/min and eptifibatide 0.5 µg/kg/min for 48 h or placebo. The primary outcomes were changes in biomarkers reflecting endothelial activation and disruption, platelet consumption and fibrinolysis. We compared groups with mixed models, post hoc Wilcoxon signed-rank test and Mann-Whitney U test. RESULTS: We included 24 patients of which 18 (12 active, 6 placebo) completed the full 7-day trial period and were included in the per-protocol analyses of the primary outcomes. Direct comparison between groups showed no differences in the primary outcomes. Analyses of within-group delta values revealed that biomarkers of endothelial activation and disruption changed differently between groups with increasing levels of thrombomodulin (p = 0.03) and nucleosomes (p = 0.02) in the placebo group and decreasing levels of sE-Selectin (p = 0.007) and sVEGFR1 (p = 0.005) in the active treatment group. Platelet count decreased the first 48 h in the placebo group (p = 0.049) and increased from baseline to day 7 in the active treatment group (p = 0.023). Levels of fibrin monomers declined in the active treatment group within the first 48 h (p = 0.048) and onwards (p = 0.03). Furthermore, there was a significant reduction in SOFA score from 48 h (p = 0.024) and onwards in the active treatment group. Intention-to-treat analyses of all included patients showed no differences in serious adverse events including bleeding, use of blood products or mortality. CONCLUSION: Our results could indicate benefit from the experimental treatment with reduced endothelial injury, reduced platelet consumption and ensuing reduction in fibrinolytic biomarkers along with improved SOFA score. The results of the CO-ILEPSS trial are exploratory and hypothesis generating and warrant further investigation in a large-scale trial. TRIAL REGISTRATION: Clinicaltrials.com, NCT02204852 (July 30, 2014); EudraCT no. 2014-002440-41.

Spectrofluorimetric determination of eptifibatide in human plasma and dosage form.

A spectrofluorimetric method for the determination of eptifibatide is presented based on its native fluorescence. The type of solvent and the wavelength of maximum excitation and emission were carefully selected to optimize the experimental conditions. Under the specified experimental conditions, the linearities obtained between the emission intensity and the corresponding concentrations of eptifibatide were in the range 0.1-2.5 µg/ml for the calibration curve constructed for direct determination of eptifibatide in dosage form and 0.05-2.2 µg/ml for the calibration curve constructed in spiked human plasma with a good correlation coefficient (r > 0.99). The lower limit of quantification for the calibration curve constructed in human plasma was 0.05 µg/ml. Recovery results for eptifibatide in spiked plasma samples and in dosage form, represented as mean ± % RSD, were 95.17 ± 1.94 and 100.29 ± 1.33 respectively. The suggested procedures were validated according to the International Conference on Harmonization (ICH) guidelines for the direct determination of eptifibatide in its pure form and dosage form and United States Food and Drug Administration (US FDA) Guidance for Industry, Bioanalytical Method Validation for the assay of eptifibatide in human plasma.

Prolonged use of eptifibatide as a bridge to maintain drug-eluting stent patency in a patient receiving extracorporeal membrane oxygenation.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has been used as a bridge to cardiac recovery in patients following a major cardiac event. There is a lack of literature surrounding prolonged use of eptifibatide and optimal dosing during ECMO. This case report describes our experience with extended durations and standard dosing of eptifibatide in the setting of ECMO. CASE: A 40-year-old male with a history of Marfan's syndrome, aortic root and ascending aortic aneurysm status post a modified Bentall with a St. Jude mechanical aortic valve conduit and hemi-Cabrol with a Dacron graft to the left main coronary artery presented with exertional chest pain and was found to have an anastomotic narrowing to the left main which occluded while awaiting surgical revision. A rescue percutaneous coronary intervention at the anastomotic site was performed. Due to hemodynamic instability, he was placed on femoral VA-ECMO. The patient was started on anticoagulation for the ECMO circuit and eptifibatide to maintain stent patency. The patient experienced several bleeding episodes for which he received supportive care, endoscopic intervention and left gastric artery embolization. Eptifibatide was maintained at standard dosing and the heparin infusion was withheld. A coronary angiogram revealed no thrombus within the Cabrol graft a patent stent previously placed at the site of the distal graft-coronary anastomosis. The patient was decannulated from ECMO and underwent coronary artery bypass grafting and division of the hemi-Cabrol graft. CONCLUSION: While eptifibatide was effective in maintaining stent patency, our patient experienced several bleeding episodes during ECMO. Thus, the risks and benefits of concurrent antiplatelet and anticoagulant therapy must be appropriately weighed in this patient population. Additionally, as the need for dual antiplatelet therapy due to coronary stent implantation is increasing, further studies are needed to validate optimal dosing of eptifibatide in patients at a high risk of bleeding during ECMO.

Ischemic Stroke After Treatment of Intraprocedural Thrombosis During Stent-Assisted Coiling and Flow Diversion.

BACKGROUND AND PURPOSE: Intraprocedural thrombosis poses a formidable challenge during neuroendovascular procedures because the risks of aggressive thromboembolic treatment must be balanced against the risk of postprocedural hemorrhage. The aim of this study was to identify predictors of ischemic stroke after intraprocedural thrombosis after stent-assisted coiling and pipeline embolization device placement. METHODS: A retrospective analysis of intracranial aneurysms treated with stent-assisted coiling or pipeline embolization device placement between 2007 and 2016 at 4 major academic institutions was performed to identify procedures that were complicated by intraprocedural thrombosis. RESULTS: Intraprocedural thrombosis occurred in 34 (4.6%) procedures. Postprocedural ischemic stroke and hemorrhage occurred in 20.6% (7/34) and 11.8% (4/34) of procedures complicated by intraprocedural thrombosis, respectively. Current smoking was an independent predictor of ischemic stroke. There was no statistically significant difference in the rate of ischemic stroke or postprocedural hemorrhage with the use of abciximab compared with the use of eptifibatide in treatment of intraprocedural thrombosis. CONCLUSIONS: Current protocols for treatment of intraprocedural thrombosis associated with placement of intra-arterial devices were effective in preventing ischemic stroke in ≈80% of cases. Current smoking was the only independent predictor of ischemic stroke.

Encapsulation of eptifibatide in RGD-modified nanoliposomes improves platelet aggregation inhibitory activity.

Eptifibatide is an antiplatelet drug used for the treatment of thrombosis. However, as a result of its accumulation in non-targeted tissues and short half-life, it has a limited efficacy. In this study, RGD-modified nano-liposomes (RGD-MNL) were prepared as carriers for the targeted delivery of eptifibatide to activated platelets. The nano-liposomes were about 90 ± 10 nm in size, with an encapsulation efficiency of 37 ± 5 % and a good stability during 21 days, with a negligible change in the size of nanoliosomes. The in vitro cytotoxicity of nanoliposomes was examined using MTT assay. The results obtained from the ex vivo study showed that the antiplatelet activity of eptifibatide encapsulated nanoliposomes was higher in comparison with the free drug (81.63 vs. 46.17 % for RGD-MNL) and (66.67 vs. 46.17 % for UNL), and this increase was more significant for nanoliposomes targeted with RGD peptide (81.63 %; p < 0.05). The results indicated that RGD-MNL encapsulated eptifibatide had no significant cytotoxic effect on cells. In conclusion, the present nanoliposome formulation can be regarded as a new delivery system for protection and enhancement of the antiplatelet activity of eptifibatide.

The Use of Eptifibatide Alone or in Combination With Heparin or Argatroban for Suspected Thrombosis in Patients With Left Ventricular Assist Devices.

Pump thrombosis and hemolysis in patients with left ventricular assist devices (LVADs) are associated with significant morbidity and mortality. Intensification of anticoagulation has been suggested as potential therapy, with mixed results. The aim of this study is to assess the safety and efficacy of adding eptifibatide with or without an anticoagulation agent in managing patients with LVAD presenting with hemolysis and suspected pump thrombosis. This retrospective single center study included all patients who presented with their first episode of suspected pump thrombosis and were treated with eptifibatide with or without an anticoagulant between March 1, 2011 and July 30, 2015. A total of 27 patients (23 HeartMate II, 4 HeartWare) were identified. The average age was 55 years (range 19-75) and time from implant to event averaged 513 days (range 35-1760). The average lactate dehydrogenase on presentation was 1111 and 63% of patients had power elevations. The average international normalized ratio (INR) on admission was 2.4, with INR of ≥2 in 21/27 patients. All patients received eptifibatide: 10 received eptifibatide only, 9 received eptifibatide and argatroban, and 8 received eptifibatide and heparin. Warfarin was continued in 25/27 patients. Overall, 21 patients (77.8%) were successfully treated medically, 5 (18.5%) underwent pump exchange, and 1 (3.7%) died. There were no differences in outcomes or complications between the three treatment groups. Despite initial success, 12/21 patients developed repeat episodes of hemolysis at 1 year. The 1-year survival in the patients treated medically was 90% and surgically was 60%. Our experience indicates that medical therapy for hemolysis and suspected LVAD thrombosis with warfarin and eptifibatide alone or in combination with argatroban or heparin appears safe and may be effective, although the episodes of recurrent hemolysis after medical management remain high.

Eptifibatide-induced thrombocytopenia leading to acute stent thrombosis.

A 71-year old female patient with inferior ST-elevation myocardial infarction underwent primary percutaneous coronary intervention (PCI) within 3 h of symptom onset. She was preloaded with 300 mg aspirin and 600 mg clopidogrel before PCI. Coronary angiogram showed occlusion of the right coronary artery. During PCI, eptifibatide was initiated due to the large thrombus burden. Few hours after the procedure, on eptifibatide infusion, a severe drop in platelet count was observed (from 210,000/µl to 35,000/µl) and the infusion was discontinued. One hour later, still under eptifibatide effect and with severe thrombocytopenia, acute stent thrombosis developed. Lack of prior heparin exposure, quick onset of thrombocytopenia made heparin induced thrombocytopenia improbable that was later excluded by specific immunoassay. However, platelet function testing suggested that eptifibatide induced thrombocytopenia was mediated by activating autoantibodies since platelet reactivity was paradoxically very high at the time of stent thrombosis but decreased radically with eptifibatide washout. The patient was successfully managed without further complications on the basis of platelet function data obtained in the subsequent days. This rare subtype of thrombocytopenia highlights that not only platelet count but also platelet function should be closely monitored in case of severe thrombocytopenia to better balance bleeding and thrombosis.

[EXPERIENCE WITH THE USE OF EPTIFIBATIDE IN ACUTE CORONARY SYNDROME DURING CORONARY INTERVENTION IN PATIENTS OLDER AGE GROUP].

Acute coronary syndrome is the leading cause of death in patients older age group. Primary PCI is nearly uncontested revascularization method because of its efficacy in reperfusion achievement and less hemorrhagic complications compared to systemic thrombolytic therapy. Nevertheless, the age of the patients is a significant bleeding risk factor, sophisticating the choice and dosing antiplatelet and anticoagulant therapy during coronary angioplasty and stenting. Blocker 2b/3a receptor eptifibatide are used to avoids the development of ischemic complications and improves myocardial perfusion, but accompanied with bleeding risk during common infusion (12-18 hours). Combined intracoronary and intravenous infusion eptifibatide during only coronary intervention enhance procedure safety.

Recombinant tissue-type plasminogen activator plus eptifibatide versus recombinant tissue-type plasminogen activator alone in acute ischemic stroke: propensity score-matched post hoc analysis.

BACKGROUND AND PURPOSE: The Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke-Enhanced Regimen (CLEAR-ER) trial demonstrated safety of recombinant tissue-type plasminogen activator (r-tPA) plus eptifibatide in acute ischemic stroke (AIS). CLEAR-ER randomized AIS patients (5:1) to 0.6 mg/kg r-tPA plus eptifibatide versus standard r-tPA (0.9 mg/kg). Interventional Management of Stroke III randomized AIS patients to r-tPA plus endovascular therapy versus standard r-tPA. Albumin in Acute Stroke Part 2 randomized patients to albumin±r-tPA versus saline±r-tPA. Our aim was to compare outcomes in CLEAR-ER combination arm patients to propensity score-matched r-tPA only subjects in Albumin in Acute Stroke Part 2 and Interventional Management of Stroke III. METHODS: The primary outcome was 90-day severity-adjusted modified Rankin score (mRS) dichotomization based on baseline National Institutes of Health Stroke Scale. Secondary outcomes were 90-day mRS dichotomization as excellent (mRS, 0-1); mRS dichotomization as favorable (mRS, 0-2); and nonparametric analysis of the ordinal mRS. RESULTS: Eighty-five combination arm CLEAR-ER subjects were matched with 169 Albumin in Acute Stroke Part 2 and Interventional Management of Stroke III trials' r-tPA only patients (controls). Median age in CLEAR-ER and control subjects was 68years; median National Institutes of Health Stroke Scale in the CLEAR-ER subjects was 11 and in control subjects 12. At 90 days, CLEAR-ER subjects had a nonsignificantly greater proportion of patients with favorable outcomes (45% versus 36%; unadjusted relative risks, 1.24; 95% confidence intervals, 0.91-1.69; P=0.18). Secondary outcomes were 52% versus 34% excellent outcomes (relative risks, 1.51; 95% confidence intervals, 1.13-2.02; P=0.007); 60% versus 53% favorable outcome (relative risks, 1.13; 95% confidence intervals, 0.90-1.41; P=0.31); and ordinal Cochran-Mantel-Haenszel P=0.10. CONCLUSION: r-tPA plus eptifibatide showed a favorable direction of effect that was consistent across multiple approaches for AIS outcome evaluation. A phase III trial to establish the efficacy of r-tPA plus eptifibatide for improving AIS outcomes is warranted.

Combined Approach to Lysis Utilizing Eptifibatide and Recombinant Tissue-Type Plasminogen Activator in Acute Ischemic Stroke-Full Dose Regimen Stroke Trial.

BACKGROUND AND PURPOSE: The Combined Approach to Lysis Utilizing Eptifibatide and Recombinant Tissue-Type Plasminogen Activator (r-tPA; CLEAR) in Acute Ischemic Stroke (AIS) and CLEAR-Enhanced Regimen (CLEAR-ER) trials demonstrated safety of reduced dose r-tPA plus the glycoprotein 2b/3a inhibitor, eptifibatide, in AIS compared with r-tPA alone. The objective of the CLEAR-Full Dose Regimen (CLEAR-FDR) trial was to estimate the rate of symptomatic intracerebral hemorrhage (sICH) in AIS patients treated with the combination of full-dose r-tPA plus eptifibatide. METHODS: CLEAR-FDR was a single-arm, prospective, open-label, multisite study. Patients aged 18 to 85 years treated with 0.9 mg/kg IV r-tPA within 3 hours of symptom onset were enrolled. After obtaining consent, eptifibatide (135 µg/kg bolus and 2-hour infusion at 0.75 µg/kg per minute) was administered. The primary end point was the proportion of patients who experienced sICH within 36 hours. An independent clinical monitor adjudicated if an sICH had occurred and an independent neuroradiologist reviewed all images. The stopping rule was 3 sICHs within the first 19 patients or 4 sICHs within 29 patients. RESULTS: From October 2013 to December 2014, 27 patients with AIS were enrolled. Median age was 73 years (range, 34-85; interquartile range, 65-80) and median National Institute of Health stroke scale score was 12 (range, 6-26; interquartile range, 9-16). One sICH (3.7%; 95% confidence interval, 0.7%-18%) was observed. CONCLUSIONS: These results demonstrate comparable safety of full-dose r-tPA plus eptifibatide with historical rates of sICH with r-tPA alone and support proceeding with a phase 3 trial evaluating full-dose r-tPA combined with eptifibatide to improve outcomes after AIS.

A matched comparison of eptifibatide plus rt-PA versus rt-PA alone in acute ischemic stroke.

BACKGROUND: The Combined Approach to Lysis Utilizing Eptifibatide and Recombinant Tissue Plasminogen Activator (rt-PA) in Acute Ischemic Stroke-Enhanced Regimen (CLEAR-ER) trial found that intravenous rt-PA plus eptifibatide (combination arm) in acute ischemic stroke (AIS) was safe and had a direction of effect that would justify a phase III trial. CLEAR-ER had unanticipated imbalances between treatment groups. We compared the rates of symptomatic intracranial hemorrhage (sICH) and good outcomes for combination therapy patients in the CLEAR-ER trial to a matched cohort of rt-PA patients from the National Institute of Neurological Disorders and Stroke (NINDS) trial. METHODS: CLEAR-ER was a multicenter, double-blind, randomized study; rt-PA-eligible AIS patients were randomized to .6 mg/kg rt-PA plus eptifibatide (135 mcg/kg bolus and .75mcg/kg/min two-hour infusion) versus standard rt-PA (.9 mg/kg). For this analysis, we matched 1:1 CLEAR-ER combination therapy patients with rt-PA arm NINDS trial patients. Patients were matched by age, gender, race, baseline modified Rankin Scale score, baseline National Institutes of Health Stroke Scale (NIHSS) score, and stroke onset to rt-PA time. RESULTS: Fifty-four matches were made. One (1.8%) sICH occurred in each group (odds ratio [OR] 1.00, 95% confidence interval [CI] .01-78.50). At 90 days, 51.8% of the CLEAR-ER group had good outcomes versus 46.3% in the NINDS rt-PA group (OR 1.30, 95% CI .57-2.96). For subjects with baseline NIHSS score > 12 (CLEAR-ER median NIHSS score), 38.5% of the CLEAR-ER group had good outcomes versus 23.1% in the NINDS group (OR 2.33, 95% CI .60-9.02). CONCLUSIONS: The safety and direction of effect of eptifibatide plus rt-PA were confirmed. A phase III trial is needed to determine the efficacy of eptifibatide plus rt-PA for improving long-term outcomes after AIS.

Glycoprotein IIb/IIIa inhibitors in the treatment of thromboembolic events related to endovascular treatment of cerebral aneurysms-systematic review and meta-analysis.

BACKGROUND AND AIMS: Thromboembolism complication is considered the most common complication associated with the treatment of endovascular. This systematic review and meta-analysis aimed to assess the studies investigating the effect of glycoprotein IIb/IIIa inhibitor agents on thromboembolic complications during endovascular aneurysm coiling. MATERIALS AND METHODS: This systematic review investigated the outcome of the use of three glycoprotein IIb/IIIa inhibitor agents (ie abciximab, tirofiban, and eptifibatide) on the thromboembolic complications during endovascular aneurysm coiling. The electronic databases of PubMed, Web of Science, Scopus, and Medline were searched up to 25 June 2021, using the keywords "Abciximab," "Tirofiban," and "Eptifibatide" incombination with "Thromboembolism Complication," "Aneurysms," and "Endovascular Aneurysm Coiling." RESULTS: A total of 21 articles were found to be eligible and included in this review. The rates of complete and partial recanalization were estimated to be 56% and 92% in patients who underwent abciximab and tirofiban therapy, respectively. Rupture aneurysms were found in the majority of patients. In general, the mortality rate of the patients treated for thromboembolic complications during endovascular treatment of cerebral aneurysms with glycoprotein IIb/IIIa inhibitors was found to be 4.8% (CI 95%:0.027-0.067; p < .005). The average remission rate in studies investigating thromboembolism was 91% (CI 95%:0.88-0.95, I2 : 65.65/p < .001). CONCLUSION: Based on the obtained results, a higher mean rate of complete recanalization by eptifibatide was found in studies in which abciximab or tirofiban were used, compared to other mentioned agents. Moreover, the amount of hemorrhage was reported to be less after using tirofiban rather than abciximab.

A woman with eptifibatide (integrilin)-induced thrombocytopenia following treatment of a clot in her coronary artery: A case report and literature review.

Eptifibatide, a GPIIb/IIIa receptor inhibitor, has shown its efficacy and safety in patients with high clot burden in their coronary vessels. It is widely used in patients with this condition. However, this medication use is accompanied by complications in some cases. Thrombocytopenia which is a relatively common condition in patients admitted to the hospital, especially in the acute setting, can be caused by medications. This condition can occur as an antibody or non-antibody-mediated process, caused by medications, such as heparin, clopidogrel, and eptifibatide. In this case, we present a woman with acute coronary syndrome and a complex lesion with a clot in her coronary vessel who was treated with eptifibatide. It led to asymptomatic thrombocytopenia. Once detected in laboratory data, the infusion was held, and the platelet count recovered in less than 5 days without additional treatment for this adverse effect. Eptifibatide is a medication used to treat acute coronary syndrome patients with a large thrombus in their coronary vessels. The mechanism of inducing thrombocytopenia by eptifibatide has not been proven yet, but it might be related to IgG antibodies. The severity of the disease can vary significantly, and the treatment is based on this factor. However, the main pillar of the treatment is the cessation of eptifibatide as soon as possible. This case draws the attention of physicians to one of the infrequent adverse effects of a commonly used medication in cardiology patients. Thrombocytopenia and its manifestations should be investigated and considered in patients who receive eptifibatide.