A Double-Blinded Randomized Controlled Trial Comparing Eptifibatide Bolus Only Versus Bolus Plus Infusion In Patients Undergoing Primary Percutaneous Coronary Intervention For ST-Elevation Myocardial Infarction.

BACKGROUNDS: The use of eptifibatide combined with heparin during percutaneous coronary intervention (PCI) in patients presenting with ST-elevation myocardial infarction (STEMI) is recommended to be followed by continuous infusion. Recently, there are some suggestions that using bolus only may be sufficient and cost-effective but randomized trials are lacking. AIMS: The goal of this study was to evaluate these two approaches in a double-blinded randomized control trial. METHODS: The primary PCI patients who received bolus eptifibatide were randomized to 75 mg IV eptifibatide infusion or placebo blindly. The patients were followed up for the primary outcome of vascular or bleeding complications and secondary outcome of ischemic complications. RESULTS: 330 patients (165 from each group) completed the study. The mean age was 57.67 ± 11.53 years and 77.3 % were male. Major bleeding was seen in 1 patient in each group. Hematoma occurred in 8.5 %. The relative risk of hematoma and ecchymosis in bolus plus infusion group to bolus only group were 0.988 (95 % CI: 0.486-2.006) and 1.032 (95 % CI: 0.729-1.459). Multivariate analysis confirmed no significant differences in the bleeding event. Furthermore, there was no significant difference in in-hospital death or any ischemic events. (Cath lab death: 1.4 % in bolus only vs zero % in the control group, p = 0.217, stent thrombosis was seen in one patient in each group). CONCLUSION: There were no differences in the risk of access site ecchymosis, hematoma or major bleeding. Ischemic events and stent thrombosis rates were also similar. Our study suggests that using eptifibatide bolus only during PCI of patients with STEMI is safe and can be cost-saving.

Intracranial stenting as a bail-out option for posthemorrhagic cerebral vasospasm: a single-center experience with long-term follow-up.

BACKGROUND: Cerebral vasospasm (CVS) is a leading cause of morbidity and mortality in patients after aneurysmal subarachnoid hemorrhage (aSAH). Endovascular treatment, including intraarterial infusion of drugs with vasodilation effects, and balloon- and stentriever angioplasty, are helpful but may achieve only short-term effects. There is a clinical need for long-lasting treatment of refractory recurrent vasospasm. We report our experience in stent implantation as a treatment for recurrent severe post-SAH vasospasm. METHODS: A retrospective analysis of our institutional database of 883 patients with SAH, managed between January 2010 and December 2021, was performed. Six patients were identified as having received intracranial stenting in the context of post-SAH cerebral vasospasm. All patients were initially treated with intra-arterial infusion of nimodipine and/or milrinone. Self-expanding intracranial stents were implanted during endovascular aneurysm treatment to enable access despite impaired perfusion (Group 1) or as a bail-out strategy after failed intraarterial drug infusion or mechanical treatment (Group 2). All stented patients received dual antiplatelet therapy (DAPT) for 6 months. RESULTS: Nine vessels in six patients with severe post-SAH vasospasm were stented. The stents were deployed in 16 vessel segments. All attempted implantations were technically successful. All patients demonstrated radiographic and clinical improvement of the vessel narrowing. No recurrent vasospasm or permanent vessel occlusion of the stented vessels was encountered. A thrombus formation in a Group 1 patient resolved under 4 mg eptifibatide IA infusion. During long-term angiographic follow-up, neither in-stent stenosis nor stent occlusion was found. CONCLUSIONS: Endovascular implantation of self-expanding stents is a potential ultima ratio strategy for patients with severe refractory post-SAH cerebral vasospasm. Stents with reduced thrombogenicity (avoiding DAPT) and bioabsorbable self-expanding stents might further advance this concept.

Bridging Antiplatelet Therapy After Percutaneous Coronary Intervention: JACC Review Topic of the Week.

Patients undergoing early surgery after coronary stent implantation are at increased risk for mortality from ischemic and hemorrhagic complications. The optimal antiplatelet strategy in patients who cannot discontinue dual antiplatelet therapy (DAPT) before surgery is unclear. Current guidelines, based on surgical and clinical characteristics, provide risk stratification for bridging therapy with intravenous antiplatelet agents, but management is guided primarily by expert opinion. This review summarizes perioperative risk factors to consider before discontinuing DAPT and reviews the data for intravenous bridging therapies. Published reports have included bridging options such as small molecule glycoprotein IIb/IIIa inhibitors (eptifibatide or tirofiban) and cangrelor, an intravenous P2Y12 inhibitor. However, optimal management of these complex patients remains unclear in the absence of randomized controlled data, without which an argument can be made both for and against the use of perioperative intravenous bridging therapy after discontinuing oral P2Y12 inhibitors. Multidisciplinary risk assessment remains a critical component of perioperative care.

Low-Dose Eptifibatide for Tandem Occlusion in Stroke: Safety and Carotid Artery Patency.

BACKGROUND AND PURPOSE: Maintaining carotid patency and avoiding symptomatic intracranial hemorrhage are competing concerns in tandem occlusions. This study provides data regarding the safety and efficacy of eptifibatide in stroke from tandem occlusion of the extracranial carotid artery and the intracranial carotid or middle cerebral artery. MATERIALS AND METHODS: This is a retrospective analysis of 58 consecutive patients who received low-dose eptifibatide (135-mcg/kg bolus, 1-mcg/kg/min infusion) during treatment of tandem occlusions. Brain imaging and carotid sonography were performed at 24-36 hours. mRS was documented at 90 days, and carotid sonography, at 30-60 days. RESULTS: The median age and NIHSS score were 64 years and 15, respectively. Twenty-five patients (43%) received tPA. ASPECTSs were 8-10 in 47 (81%) and 5-7 in 11 (19%) patients. Thirty-eight patients had angioplasty/stent placement acutely; 20 had angioplasty alone. Symptomatic intracranial hemorrhage occurred in 1 patient (2%). TICI 2b or higher was achieved in 56 patients (96%). Fifty-seven of 58 patients had clinical follow-up at 90 days (1 lost to follow up). The 90-day mRS was 0-2 in 42 patients (72%). There were 4/58 (7%) re-occlusions within 24-36 hours, all originally treated with stent placement. Forty-nine of 53 surviving patients had carotid sonography at 30-60 days, with 3 delayed re-occlusions, 2 with stents and 1 with angioplasty alone. The overall carotid patency at 30-60 days was 42/49 (86%). Carotid re-occlusion was not associated with clinical decline. CONCLUSIONS: Low-dose eptifibatide seemed to be safe in tandem occlusions (symptomatic intracranial hemorrhage, 2%), although asymptomatic cervical carotid artery re-occlusions still occurred in 14% of patients.

Prevalence, clinical determinants and prognostic implications of coronary procedural complications of percutaneous coronary intervention in non-ST-segment elevation myocardial infarction: Insights from the contemporary multinational TAO trial.

BACKGROUND: Few data are available on procedural complications of percutaneous coronary intervention (PCI) in the setting of acute coronary syndrome in the contemporary era. AIM: We sought to describe the prevalence of procedural complications of PCI in a non-ST-segment elevation acute coronary syndrome (NSTE ACS) cohort, and to identify their clinical characteristics and association with clinical outcomes. METHODS: Patients randomized in TAO (Treatment of Acute coronary syndrome with Otamixaban), an international randomized controlled trial (ClinicalTrials.gov Identifier: NCT01076764) that compared otamixaban with unfractionated heparin plus eptifibatide in patients with NSTE ACS who underwent PCI, were included in the analysis. Procedural complications were collected prospectively, categorized and adjudicated by a blinded Clinical Events Committee, with review of angiograms. A multivariable model was constructed to identify independent clinical characteristics associated with procedural complications. RESULTS: A total of 8656 patients with NSTE ACS who were enrolled in the TAO trial underwent PCI, and 451 (5.2%) experienced at least one complication. The most frequent complications were no/slow reflow (1.5%) and dissection with decreased flow (1.2%). Procedural complications were associated with the 7-day ischaemic outcome of death, myocardial infarction or stroke (24.2% vs. 6.0%, odds ratio 5.01, 95% confidence interval 3.96-6.33; P<0.0001) and with Thrombolysis In Myocardial Infarction major and minor bleeding (6.2% vs. 2.3%, odds ratio 2.79, 95% confidence interval 1.86-4.2; P<0.0001). Except for previous coronary artery bypass grafting, multivariable analysis did not identify preprocedural clinical predictors of complications. CONCLUSIONS: In a contemporary NSTE ACS population, procedural complications with PCI remain frequent, are difficult to predict based on clinical characteristics, and are associated with worse ischaemic and haemorrhagic outcomes.

Adjunctive treatment with low dose intra-arterial eptifibatide and intravenous aspirin during carotid stenting: A case series.

PURPOSE: According to most guidelines, medical protocol for carotid stenting includes the administration of oral Aspirin and Clopidogrel at least four days before the procedure, with intraprocedural intravenous (IV) heparin. Some publications have also reported the safety of adding glycoprotein 2b/3a inhibitors to the protocol. In this retrospective study, we evaluate the safety of a new medication protocol that includes IV aspirin and intra-arterial Eptifibatide (glycoprotein 2b/3a inhibitor) during carotid stenting. All patients who underwent carotid stenting at Soroka University Medical Center between January 2015 and May 2020 were included (emergent cases were excluded). We divided patients into two groups-patients treated under the standard protocol, and patients treated under the new protocol. In the latter, patients received both the standard protocol regimen, as well as 150 mg IV aspirin immediately before stenting, and a slow intra-arterial injection of 2-3 mg Eptifibatide (glycoprotein 2b/3a antagonist) immediately after stenting. Forty-four patients were treated according to the standard protocol (group 1), and 41 patients were treated according to the new protocol (group 2). In group 1, six patients had complications, while in group 2, no complications of any kind were noted (p = 0.027). The safety and possible efficacy of this novel protocol was preliminarily demonstrated in the present study. Future studies are needed to prove the safety and efficacy of a specific drug regimen that will further reduce the complication rates of carotid stenting.

Acute myocardial infarction and large coronary thrombosis in a patient with COVID-19.

This is a case report of a 60-year-old male, without any cardiovascular risk factor and no cardiac history admitted to hospital with a diagnosis of interstitial pneumonia caused by coronavirus disease 2019 (COVID-19). After 7 days, the blood tests showed a significant rise of inflammatory and procoagulant markers, along with a relevant elevation of high-sensitivity Troponin I. Electrocardiogram and transthoracic echocardiogram (TTE) were consistent with a diagnosis of infero-posterolateral acute myocardial infarction and the patient was transferred to the isolated Cath Lab for primary percutaneous coronary intervention (PCI). The angiography showed an acute massive thrombosis of a dominant right coronary artery without clear evidence of atherosclerosis. Despite the optimal pharmacological therapies and different PCI techniques, the final TIMI flow was 0/1 and after 3 hr the clinical condition evolved in cardiac arrest for pulseless electric activity. Acute coronary syndrome-ST-elevation myocardial infarction is a relevant complication of COVID-19. Due to high levels of proinflammatory mediators, diffuse coronary thrombosis could occur even in patients without cardiac history or comorbidities. This clinical case suggests that coronary thrombosis in COVID-19 patients may be unresponsive to optimal pharmacological (GP IIb-IIIa infusion) and mechanical treatment (PCI).

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.

Routine Glycoprotein IIb/IIIa Inhibitor Therapy in ST-Segment Elevation Myocardial Infarction: A Meta-analysis.

BACKGROUND: Guidelines recommend adjunct glycoprotein IIb/IIIa inhibitors (GPIs) only in selected patients with acute ST-segment elevation myocardial infarction (STEMI). This study aimed to evaluate routine GPI use in STEMI treated with primary percutaneous coronary intervention. METHODS: Online databases were searched for randomized controlled trials of routine GPI vs control therapy in STEMI. Data from retrieved studies were abstracted and evaluated in a comprehensive meta-analysis. Twenty-one randomized controlled trials with 8585 patients were included: 10 trials randomized tirofiban, 9 abciximab, 1 trial eptifibatide, and 1 trial used abciximab+tirofiban; only 1 trial used dual antiplatelet therapy with prasugrel/ticagrelor. RESULTS: Routine GPI use was associated with a significant reduction in all-cause mortality at 30 days (2.4% [GPI] vs 3.2%; risk ratio [RR], 0.72; P = 0.01) and 6 months (3.7% vs 4.8%; RR, 0.76; P = 0.02), and a reduction in recurrent myocardial infarction (1.1% vs 2.1%; RR, 0.55; P = 0.0006), repeat revascularization (2.5% vs 4.1%; RR, 0.63; P = 0.0001), thrombolysis in myocardial infarction flow <3 after percutaneous coronary intervention (5.4% vs 8.2%; RR, 0.61; P < 0.0001), and ischemic stroke (RR, 0.42; P = 0.04). Major (4.7% vs 3.4%; RR, 1.35; P = 0.005) and minor bleedings (7.2% vs 5.1%; RR, 1.39; P = 0.006) but not intracranial bleedings (0.1% vs 0%; RR, 2.7; P = 0.37) were significantly increased under routine GPI. CONCLUSIONS: Routine GPI administration in STEMI resulted in a reduction in mortality, driven by reductions in recurrent ischemic events-however predominantly in pre-prasugrel/ticagrelor trials. Trials with contemporary STEMI management are needed to confirm these findings.

Comparison of Routine Versus Selective Glycoprotein IIb/IIIa Inhibitors Usage in Primary Percutaneous Coronary Intervention (from the British Cardiovascular Interventional Society).

The role of glycoprotein IIb/IIIa inhibitors (GPI) in primary percutaneous coronary intervention (PPCI) remains uncertain. Previous analyses compare PPCI outcomes with clopidogrel plus GPI, versus without GPI. This does not reflect modern contemporary PPCI practice with ticagrelor or prasugrel. Nor does it answer the important question faced daily by PPCI operators: should GPI be used routinely or selectively? We aim to determine whether a strategy of routine use of GPI in contemporary PPCI practice is superior to selective GPI use. A total of 110,327 consecutive PPCIs performed in England were prospectively recorded in the British Cardiovascular Intervention Society Database (2009 to 2015). The cohort was divided into routine and selective GPI usage groups based on the PPCI operator's strategy, defined as GPI used in >75% and <25% PPCIs, respectively. Overall, GPI use declined from 73.1% to 43.3% of PPCIs. Routine compared with selective GPI usage was associated with lower all-cause 1-year mortality: 9.7% versus 11.0%, p < 0.001. There was a consistent survival benefit for routine GPI usage as compared with selective GPI usage: univariable analysis (hazard ratio = 0.88 [95% confidence interval 0.83 to 0.93], p < 0.001), multivariable analysis (hazard ratio = 0.82 [0.77 to 0.88], p < 0.001). For survival, there was no interaction between GPI usage and the type of P2Y12-inhibitor used. In conclusion, a strategy of routine GPI usage in patients who underwent PPCI was associated with lower all-cause mortality as compared with selective GPI usage. This benefit was maintained despite 44.3% of patients receiving prasugrel or ticagrelor.

Use of the PulseRider Device in the Treatment of Ruptured Intracranial Aneurysms: A Case Series.

BACKGROUND: Wide-necked intracranial aneurysms present unique treatment challenges in the setting of subarachnoid hemorrhage. New generations of endoluminal devices (stents) have expanded our ability to treat complex aneurysms. The PulseRider Aneurysm Neck Reconstruction Device (PulseRider [Cerenovus, Irvine, California, USA]) is new to the U.S. market after receiving Food and Drug Administration approval in June 2017. Official recommendation for use of the PulseRider is with dual antiplatelet therapy (DAPT). Its design has been hypothesized to carry a lower risk of thromboembolic complications in the circumstance that DAPT needs to be discontinued. METHODS: Between March and June 2018, we treated 4 cases of ruptured wide-necked basilar tip aneurysms at the University of Colorado Hospital, Aurora, Colorado, with PulseRider-assisted coil embolization. Imaging and chart reviews were performed retrospectively on each of these patients. RESULTS: All 4 aneurysms were successfully treated with PulseRider-assisted coil embolization. There were no periprocedural hemorrhages and no postprocedural reruptures. Two patients developed nonocclusive thrombi in the posterior cerebral arteries at the time of coiling, which was resolved with intra-arterial glycoprotein IIb/IIIa receptor antagonists. Two patients developed external ventricular drain-associated hemorrhages, only one of which developed after the administration of DAPT. All patients were eventually discharged to home. CONCLUSIONS: The PulseRider device represents a novel design for stent-assisted coil embolization. We report a small but promising series of its successful use in the acute treatment of wide-necked, ruptured basilar artery aneurysms. Additional experience is needed to determine if this device has a place in our armamentarium for treatment of ruptured aneurysms.

Novel Antiplatelet Perioperative Bridging Protocol for Lung Lobectomy: A Case Report.

INTRODUCTION: Some patients with cardiac stents will need thoracic surgery during the dual antiplatelet therapy (DAPT) period. When surgery cannot be safely delayed to allow 1 year of uninterrupted DAPT, appropriate perioperative management of anticoagulation is critical. CASE PRESENTATION: A patient treated with new drug-eluting stents and DAPT was concomitantly diagnosed with lung cancer and required a lobectomy. We describe the novel addition of ticagrelor (a short-acting oral antiplatelet agent) to eptifibatide (a short-acting intravenous antiplatelet agent) to bridge DAPT for surgery. DISCUSSION: This ticagrelor-eptifibatide perioperative bridge resulted in decreased preoperative hospitalization compared with eptifibatide alone. There were no associated perioperative cardiac or bleeding complications.

Impact of Selective Aspiration Thrombectomy on Mortality in Patients With ST-Segment Elevation Myocardial Infarction.

Although routine aspiration thrombectomy (AT) is not recommended by the current American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions guideline, for selected cases, a class IIb indication is given because of lack of data. We studied the impact of selective AT on mortality in patients with ST-segment elevation myocardial infarction using a prospective registry. We analyzed data of 1,255 patients, of whom 535 underwent AT based on operator's decision. Separate propensity score matching procedures were performed including all patients and only those with initial TIMI (Thrombolysis In Myocardial Infarction) 0 to 1 flow, indicating the highest thrombus burden. Primary outcome measure was time to all-cause death at 1 year. Both studies were sufficiently powered to detect the hazard ratio (HR) of 0.52 seen in the TAPAS (Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study) trial. In the study with open inclusion criteria, 1-year mortality rates were 15.5% and 14.5% in the AT and conventional percutaneous coronary intervention arm, respectively (p = 0.77). The unadjusted HR was 1.05 (95% CI 0.73 to 1.51), p = 0.80, whereas the adjusted HR was 0.97 (95% CI 0.66 to 1.41), p = 0.87. In patients with initial TIMI 0 to 1 flow, mortality rate at 1 year was 15.6% in the AT and 16.7% in the standard percutaneous coronary intervention group (p = 0.76). The unadjusted and adjusted HRs were similar: 0.91 (95% CI 0.62 to 1.34), p = 0.65 and 0.93 (95% CI 0.62 to 1.37), p = 0.70, respectively. In conclusion, selective AT based on operator's discretion offers no mortality benefit of the magnitude detected in the TAPAS trial, even for patients with initial TIMI 0 to 1 flow grade.

Glycoprotein IIb/IIIa Inhibitors in Prevention and Rescue Treatment of Thromboembolic Complications During Endovascular Embolization of Intracranial Aneurysms.

Thromboembolic complications remain a major risk of endovascular neurosurgery during the treatment of intracranial aneurysms, despite the use of therapeutic heparinization and oral antiplatelet therapy when indicated. Glycoprotein (GP) IIb/IIIa inhibitors target a nonredundant pathway of platelet aggregation following adhesion and activation. Initially established and implemented in the cardiovascular arena, this drug class has provided a new tool in the neurovascular armamentarium as well. Numerous case reports, case series, and retrospective reviews have evaluated the safety and efficacy of abciximab, eptifibatide, and tirofiban in the treatment of acute thromboembolic complications during the endovascular treatment of intracranial aneurysms. The use of this drug class has also been found to be beneficial as a prophylactic agent, providing ischemia protection during the placement of intracranial stents, flow diverters, and thrombogenic coils in the setting of subarachnoid hemorrhage and during elective aneurysmal embolization. While the current published literature clearly establishes efficacy and safety of GP IIb/IIIa inhibitors in the prevention of thromboembolic complications, there does not yet exist an established protocol for their administration in endovascular neurosurgery. This review provides a comprehensive evaluation of the current published literature pertaining to the use of all available GP IIb/IIIa inhibitors for thromboembolic complications, providing recommendations for dosing and administration of abciximab, eptifibatide, and tirofiban based on previously published rates of efficacy and intracranial hemorrhage.

Immediate & Short Term Outcome of Using Single Bolus Eptifibatide in Percutaneous Coronary Intervention: A Randomized Control Study.

The purpose of this study was to assess the immediate and short term outcome of single bolus dose of eptifibatide in elective percutaneous coronary intervention (PCI). We enrolled 146 patients who underwent elective PCI from May 2013 to May 2014 in University Cardiac Centre, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. Among 146 patients, seventy four patients received single bolus dose of eptifibatide (10 mg intra coronary single bolus dose) just after crossing the lesion were selected as case. The other 72 patients, who did not receive eptifibatide, were selected as control. All patients of both the groups were treated with aspirin, clopidogrel before and after the procedure and all received a single bolus dose of Clopidogrel (300mg) before the procedure. All patient received weight adjusted doses of heparin during and after the procedure. The outcome measures were 24-hours and 30-day morbidity (complications or adverse events) and mortality. The patients of eptifibatide group experienced significantly lower incidence of QMI lesions and complete absence of NQMI lesion in 24 hours of PCI as compared to 5.6% and 6.9% of the lesions respectively in their control counterparts (p=0.027 and p=0.025 respectively). However, the incidence of bleeding and target vessel revascularization (TVR) were no different between the groups (p=0.255 and p=0.117). There was no incidence of TVR at all in the eptifibatide group as opposed to 5.6% in the control group in 30 days following stenting (p=0.017). Single bolus dose of eptifibatite reduces the Major adverse cardiac events as immediate and short term outcome in elective percutaneous coronary intervention.