Intravenous Antiplatelet Agents Research Articles

Pediatric inflammatory multisystem syndrome or Kawasaki disease - continuous challenges in Pediatrics - case report

Introduction. Kawasaki disease (KD) and pediatric inflammatory multisystem syndrome (PIMS) are similar vasculitis conditions affecting medium and small vessels, particularly the coronary arteries. This study aimed to highlight diagnostic and treatment challenges in a case initially diagnosed as PIMS, which evolved into atypical KD. Materials and methods. A 2-year-10-month-old male was admitted with a high fever persisting for 6 days, unresponsive to antipyretics. Results. On admission, the patient exhibited a poor general condition, pale skin, non-pruritic erythematous rash, and enlarged, non-painful lymph nodes. Laboratory tests showed elevated inflammatory markers, leukocytosis with neutrophilia, hypoalbuminemia, liver enzyme abnormalities, altered cardiac markers, and elevated D-dimers, but no initial echocardiographic changes. Positive SARS-CoV-2 antibodies led to an initial PIMS diagnosis, and treatment with intravenous methylprednisolone, antiplatelet, anticoagulant therapy, and hepatoprotective agents was started. The patient’s condition initially improved but then worsened with febrile spikes, rash, neutropenia, thrombocytopenia, anemia, and coronary artery dilation on echocardiography. This led to a diagnosis of KD with atypical onset, and treatment with immunoglobulin, antiplatelet, and anticoagulant therapy was initiated. The patient’s condition improved slowly. Conclusions. KD and PIMS share overlapping characteristics, making them difficult to distinguish. There is no definitive criterion to differentiate KD and PIMS, leading to potential diagnostic errors.

Anticoagulation Management During a Spinal Cord Stimulator Trial on a Patient With ST-Elevation Myocardial Infarction

BACKGROUND: Spinal cord stimulators (SCSs) are indicated for the treatment of many pain syndromes. They are often trialed prior to placement of a permanent implant. Patients on anticoagulation therapy are instructed to follow the American Society of Regional Anesthesia and Pain Medicine guidelines during this process. CASE REPORT: Here we describe a unique case of a patient who had an SCS trial, followed by an ST-elevation myocardial infarction (STEMI) on day 4 postimplantation. After coronary revascularization, the patient started dual antiplatelet therapy, which posed significant for epidural hematoma with recent stimulator implantation. CONCLUSIONS: The patient was bridged with intravenous antiplatelet agents prior to SCS trial removal and monitored closely. Our discussion will focus on all anticoagulation management of patients with a recent STEMI who had undergone a trial SCS implantation. KEY WORDS: Spinal cord stimulation, neuromodulation, chronic pain, anticoagulation

Geographic differences in pharmacotherapy patterns and outcomes of acute ischemic stroke in China

BackgroundVast economic and healthcare status discrepancies exist among regions in China, contributing to different treatment patterns. This study was aimed to investigate the current status of pharmacotherapy for acute ischemic stroke (AIS) and outcomes in China and explore the geographic variation in stroke care.MethodsThis study was a multicenter prospective registry study, which collected the data of patients with AIS from 80 hospitals in 46 cities in 2015–2017 across China. Poor functional outcome defined as a modified Rankin Scale score of 3–6 was assessed at 3 and 12 months. Multivariate logistic regression was used.ResultsAmong 9973 eligible patients, the number of receiving intravenous thrombolysis (IVT), antiplatelet agents, anticoagulants, statin and human urinary kallidinogenase was 429 (4.3%), 9363 (93.9%), 1063 (10.7%), 6828 (74.7%) and 5112 (51.2%), respectively. Multivariable analysis showed IVT use in northeastern was significantly more frequent than in eastern region (OR = 3.17, 95% CI, 2.53–3.99), while the antiplatelets agents use were less frequent (OR = 0.46, 95%CI: 0.38–0.57). The proportions of poor outcomes at 3 and 12 months were 20.7% and 15.8%, respectively. Multivariate analysis showed AIS patients from northeastern and central region had significantly lower risk of poor outcome at month 3 and 12 than those from eastern region (all P < 0.05).ConclusionsThere was a low IVT use and a high antiplatelet agent and statin use for AIS in China. The pharmacotherapy and prognosis of AIS had variation by geographic region.Trial registrationThis study was registered with ClinicalTrials.gov (NCT02470624).

Current Status and Future Direction of Antithrombotic Therapy for Patients with STEMI Undergoing Primary PCI.

Since the introduction of the first pharmacological therapy for the treatment of patients with acute myocardial infarction in the early 20th century, treatment of myocardial infarction has evolved extensively throughout the years. Mechanical revascularization therapies such as the percutaneous transluminal coronary angioplasty, combined with the ongoing development of pharmacological therapies have successfully improved the survival of patients with acute myocardial infarction. To date, antiplatelet therapy (consisting of aspirin and an oral inhibitor) and anticoagulation therapy represent the main stay of pharmacological treatment in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). The routine use of clopidogrel as antiplatelet agent has been largely replaced by the use of the more potent inhibitors ticagrelor and prasugrel. Unfractionated heparin remains the preferred anticoagulant therapy, despite the development of other anticoagulants, including enoxaparin and bivalirudin. To date, limited evidence exists supporting a pre-hospital initiation of antiplatelet and anticoagulant therapy in STEMI patients. The use of potent intravenous antiplatelet agents, including the glycoprotein IIb/IIIa inhibitors and the intravenous inhibitor cangrelor, is currently restricted to specific clinical settings. While several potent antithrombotic agents already exist, the search for novel potent antithrombotic agents continues, with a focus on balancing antithrombotic properties with an improved safety profile to reduce excess bleeding. This review provides an overview of currently available pharmacological therapies for the treatment of STEMI patients undergoing primary PCI, and an outlook for the ongoing development of novel agents in this field.

Pharmacological Interventions to Prevent Clotting in Extracorporeal Circuits During Continuous Renal Replacement Therapy

What are the risks and benefits of pharmacological interventions to prevent clotting in extracorporeal circuits during continuous renal replacement therapy (CRRT)?Patients who are critically ill in an intensive care unit often develop kidney complications related to multiple factors such as infection, hypotension, and necessary medications. Acute kidney injury occurs in approximately 11% to 18% of hospitalized patients and contributes to an estimated 1.7 million deaths every year.1 Because these patients are hemodynamically unstable, they cannot tolerate standard dialysis, which is typically a 3- to 4-hour procedure. Instead, continuous dialysis is the treatment of choice, and critically ill patients often tolerate it better. This continuous treatment, known as CRRT, provides opportunities for the health care team to introduce treatment modalities that would otherwise cause waste products and fluid to accumulate within the injured kidneys.2Standard practice is to run CRRT continuously for 24 hours; however, the therapy is often inadvertently stopped for periods of time because of clotting in the circuits. When such clotting occurs, the circuits must be changed immediately. The need to change the circuits not only delays treatment but also takes staff time and adds costs. To maintain the full therapeutic effect of CRRT, reducing any interruptions to therapy is essential.2During CRRT, blood contacts the circuit system, which can activate the coagulation pathway. Pharmacological approaches to avoid clotting in CRRT circuits involve several medications including intravenous anticoagulants (eg, unfractionated heparin [UFH], low-molecular-weight heparin, argatroban, citrate), oral anticoagulants (warfarin), and antiplatelet agents.3 The purpose of this systematic review was to assess the benefits and harms of pharmacological interventions for preventing clotting in extracorporeal circuits during CRRT.This systematic review, conducted by Tsujimoto et al,4 included 34 randomized controlled trials (and some quasi-experimental trials) comprising 1960 adult participants. The main primary outcomes investigated included major bleeding, successful prevention of clotting (defined as not needing a circuit change during the first 24 hours), and death from any cause at day 28. The included studies evaluated many different pharmacological comparisons; the most common were heparin derivatives and citrate. Because citrate and UFH are the most commonly used medications to prevent clotting during CRRT,2 this summary describes only the comparison of these 2 interventions.Tsujimoto et al4 independently assessed the risk of bias for each study, including selection, performance, detection, attrition, reporting, and publication biases. They resolved any disagreements by reviewing the data together and through discussion. For dichotomous outcomes, risk ratios (RRs) with 95% CIs were used as measures of treatment effect between various comparisons and outcomes. The authors also used the internationally approved Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to determine the certainty of evidence—high, moderate, low, or very low—for each outcome5: This review showed that, when comparing citrate with UFH to prevent clotting during CRRT, moderate-certainty evidence supports citrate resulting in less major bleeding and having slightly more success at the prevention of clotting.4 The findings from this systematic review align with those of other studies showing that citrate, when compared with UFH, more effectively prolongs the duration of CRRT circuits and reduces the risk of bleeding.6 Currently, several ongoing studies could, once completed or published, be included in similar assessments in future systematic reviews.4The evidence from this systematic review can affect clinical care teams’ decisions when they are creating treatment plans for patients in this population. As nurses caring for critically ill patients, advocating for the best evidence-based treatment remains an important piece of our role. We must always consider the best available evidence and understand the feasibility, appropriateness, meaningfulness, and effectiveness of any intervention to determine whether it is most appropriate to implement in our individual context.

P126 THE DANGEROUS LINK BETWEEN ECTOPIC ADIPOSITY AND HIGH RISK ATHEROSCLEROSIS: A PARADIGMATIC CASE OF STEMI

Abstract Nowadays CCTA has become the first line diagnostic tool in the clinical management of CAD thanks to its outstanding performance in assessing both the degree of stenosis and coronary plaques features, with crucial prognostic implications. Furthermore, CTCA allows an accurate quantification of epicardial fat, which has been shown to be a metabolic active tissue that by means of inflammatory mediators influences the development of high risk plaques and atrial fibrillation. A 70–years–old man underwent primary PCI for an acute STEMI. He was a former smoker with a history of obesity, hypertension, hypercholesterolemia and type II diabetes, without previous major cardiovascular events or significant comorbidities. The coronary angiography revealed diffuse coronary artery ectasia and a thrombotic total occlusion of the proximal portion of the RCA. After intravenous antiplatelet agent administration, balloon angioplasty was performed and three drug eluting stents were implanted. Furthermore, since the coronary angiography showed a calcific contour travelling parallel to the RCA course, in order to rule out a thrombosed coronary pseudoaneurysm, a CTCA was performed. CTCA unexpectedly revealed an enormous fibro–fatty plaque surrounded by a calcific shell in the RCA ostium–proximal segment, with the stents located at one border of the plaque, well expanded inside the vessel lumen. The post–procedural hospital stay was marked by new onset Atrial Fibrillation, unresponsive to pharmacological cardioversion. In contrast with coronary invasive angiography, CT was able to detect a very high plaque burden and a salient ubiquitary epicardial fat volume. In addition, at the site of the culprit lesion, CT showed huge plaque volume with an extreme eccentrically positive vessel remodeling, large low attenuation areas and spotty calcifications, all features known to predict adverse coronary events. This case shows how the combination of metabolic syndrome and ectopic fat accumulation fosters a milieu conducive for high risk atherosclerosis and its clinical complications.

Thrombectomy for Large‐Vessel Occlusion With Pretreatment Intracranial Hemorrhage

Background Many patients treated with endovascular thrombectomy (EVT) in clinical practice would not have qualified for inclusion in the initial clinical trials demonstrating benefit for EVT, yet likely will benefit from reperfusion. One such subset for which data are sparse is patients with emergent large‐vessel occlusion and concomitant intracranial hemorrhage (ICH). The objective of this report is to document patients who underwent thrombectomy for large‐vessel occlusion in the presence of concomitant ICH and evaluate their clinical characteristics and outcomes. Methods We retrospectively reviewed prospectively collected patient records at 4 comprehensive stroke centers from 2012 to 2019. Patients were identified who had pre‐EVT ICH. Data collected included baseline patient demographics and laboratory values, stroke characteristics, ICH radiographic variables, antiplatelet/anticoagulant/thrombolytic medication use, and procedural factors. The primary safety outcome was any worsening of ICH on neuroimaging obtained 24 hours after EVT. Results Eight patients were identified who underwent thrombectomy with concomitant ICH. The mean age was 71.9 years (range, 37–90). Median National Institutes of Health Stroke Scale score was 25 (interquartile range, 16.5–28.8), and 5 (63%) received tissue plasminogen activator. All patients underwent EVT and had mTICI2B or greater reperfusion. In 7 patients (88%), the initial ICH remained stable on postprocedure imaging. In 1 patient who received intravenous antiplatelet agents during thrombectomy, the hemorrhagic transformation was radiographically increased but without clinical correlate or mass effect. Conclusions In a multi‐institution evaluation of 8 patients with ICH at the time of thrombectomy, 1 patient had radiographic worsening of hemorrhage, and no patient experienced clinical worsening related to hemorrhage progression. These findings suggest that thrombectomy may be safe in this population.

Pre-Hospital Antiplatelet Therapy for STEMI Patients Undergoing Primary Percutaneous Coronary Intervention: What We Know and What Lies Ahead.

Early recanalization of the infarct-related artery to achieve myocardial reperfusion is the primary therapeutic goal in patients with ST-elevation myocardial infarction (STEMI). To decrease the duration of ischaemia, continuous efforts have been made to improve pre-hospital treatment and to target the early period after symptom onset. In this period the platelet content of the fresh coronary thrombus is maximal and the thrombi are dynamic, and thus more susceptible to powerful antiplatelet agents. There have been substantial advances in antiplatelet therapy in the last three decades with several classes of oral and intravenous antiplatelet agents with different therapeutic targets, pharmacokinetics, and pharmacodynamic properties. New parenteral drugs achieve immediate inhibition of platelet aggregation, and fast and easy methods of administration may create the opportunity to bridge the initial gap in platelet inhibition observed with oral P2Y12 inhibitors. Moreover, potential future management of STEMI could directly involve patients in the process of care with self-administered antiplatelet agents designed to achieve rapid reperfusion. However, the potential anti-ischaemic benefits of potent antiplatelet agents will need to be balanced against their risk of increased bleeding. This study presents a comprehensive and updated review of pre-hospital antiplatelet therapy among STEMI patients undergoing primary percutaneous intervention and explores new therapies under development.

Antiplatelet Therapy During Emergent Extracranial Internal Carotid Artery Stenting: Comparison of Three Intravenous Antiplatelet Perioperative Strategies

IntroductionGuidelines for antiplatelet therapy administration, during emergent stenting for extra-cranial internal carotid artery (EC-ICA) occlusion in the setting of acute ischemic stroke (AIS) are lacking. Different antiplatelet regimen are used in association to endovascular therapy (EVT) for the treatment of EC-ICA lesions. We aimed to compare the clinical and radiological effects of three intravenous antiplatelet agents used during emergent EC-ICA stenting. Material and MethodsClinical data were collected from January 2015 to December 2019 in a monocentric prospective registry of AIS patients treated by EVT. All patients who underwent emergent EC-ICA stenting were sorted regarding the intravenous antiplatelet agent used during the procedure. ResultsAmong 218 patients treated by EVT for an EC-ICA occlusion of the anterior circulation during the study period, 70 underwent an emergent stenting of the EC-ICA. 60 were included in the present study, 9 received intravenous (IV) Cangrelor, 8 IV abciximab and 43 Aspirin. The rate of favorable neurological outcome, defined as modified Rankin Scale (mRS) ≤ 2 at three months were better in the Cangrelor and Aspirin groups (66,7% and 58,1%, respectively) than in the Abciximab group (37,5%), as well as, the rate of any intracranial ICH (22,2% and 37,2% vs 62,5%). The rate of acute stent reocclusion was similar between groups. ConclusionWhen used as a rescue treatment during emergent stenting of EC-ICA, Cangrelor and Aspirin present a better safety profile than Abciximab, with less intracranial hemorrhages and a higher rate of good clinical outcome. Additional studies are needed to confirm these findings.

Use of Continuous Infusions of Eptifibatide and Cangrelor in Large Vessel Occlusion Acute Ischemic Stroke After Emergent Carotid Artery Stenting

Placement of carotid stents in the setting of large vessel occlusion (LVO) is sometimes necessary in patients with steno-occlusive disease of the extracranial internal carotid artery (ICA) or ICA dissection. Use of antiplatelet agents is required to prevent in-stent thrombosis; however, after an LVO, a decompressive hemicraniectomy may be necessary. After placement of a carotid stent, a fine balance must be obtained between preventing stent-related thromboembolic complications while also maintaining the possibility of quickly and safely performing a decompressive hemicraniectomy, if indicated. In this case, we discuss the novel use of continuous eptifibatide and cangrelor infusions after carotid stent placement to maintain stent patency, while preserving the option of emergent hemicraniectomy. A 55-year-old man presented with left hemispheric ischemic symptoms due to flow failure from a left ICA dissection. He underwent emergent angiography with angioplasty and stenting of the petrous and ascending cervical segments of the left ICA. The procedure was complicated by an embolization of thrombus to a left middle cerebral artery (MCA) M2 division branch, resulting in an occlusion, which could not be opened. The patient was placed on short acting intravenous antiplatelet agents (eptifibatide infusion for 60 h and cangrelor infusion for 24 h) for prevention of in-stent thrombosis while under close observation for potential neurologic decline and need for decompressive hemicraniectomy. After 84 h of observation, the patient did not experience a decline and the antiplatelet infusions were discontinued after he received aspirin and a loading dose of clopidogrel. Intravenous eptifibatide or cangrelor infusions are short-acting antiplatelet options that can be used in patients with acute ischemic stroke from LVO in the setting of ICA stent placement when there exists a potential for decompressive hemicraniectomy. J Neurol Res. 2020;10(3):99-103 doi: https://doi.org/10.14740/jnr591

Does morphine remain a standard of care in acute myocardial infarction?

Morphine is routinely used for pain relief in patients with acute myocardial infarction. However, it was documented that morphine decreases the bioavailability and antiplatelet effect of P2Y 12 receptor inhibitors. Multiple strategies to overcome this undesirable interaction are currently under investigation; they include the follwing: administration of crushed ticagrelor tablets, co-administration of metoclopramide, bridging with intravenous antiplatelet agents, or replacement of morphine with other analgesic. Adequately powered randomised trials examining the clinical consequences of concomitant use of morphine and P2Y 12 receptor inhibitors are still lacking.

Balloon coronary angioplasty and parenteral antiplatelet therapy for intraoperative myocardial infarction during general surgery: An attempt to balance benefits and risks - a case report

Introduction. Cardiovascular complications remain one of the major risk factors for perioperative morbidity and bad outcome in non-cardiac surgery patients. Here we report a case of the patient suffering intraoperative ST-segment elevation acute myocardial infarction (STEMI) promptly treated with percutaneous balloon angioplasty and intravenous antiplatelet agents. Case report. A 62-year-old man, without previous history of cardiovascular morbidity, developed STEMI during abdominal surgery. Due to profound hypotension with mean arterial pressure of less than 40 mmHg, surgery was promptly ended and patient transferred to intensive care unit. Within one hour after the end of the surgery, coronary angiography and successful balloon angioplasty of occluded right coronary artery were performed. Tirofiban infusion was started in recommended dose. Developed hemodynamic instability was related to hypovolemia and excessive drainage, reaching 1,500 mL of blood in the following 15 hours. The following morning, drainage persisted (additional 600 mL of blood) which resulted in profound hypotension (65/40 mmHg). Overall, the patient received 1,970 mL of blood, 6 doses of thrombocytes and 840 mL of fresh frozen plasma. All together, the patient had a favorable outcome, despite the occurrence of bleeding complications and hemodynamic instability. Conclusion. The choice of treatment strategy for patients suffering perioperative STEMI during major non-cardiac surgery is challenging. After major non-cardiac surgery, characterized by both high bleeding risk and high risk of stent thrombosis, balloon angioplasty instead of stenting along with parenteral antiplatelet treatment may be a fair therapeutic choice. Clinical choices have to be made individually, according to the weighted risks and benefits.

Use of Continuous Infusions of Eptifibatide and Cangrelor in Large Vessel Occlusion Acute Ischemic Stroke After Emergent Carotid Artery Stenting

Placement of carotid stents in the setting of large vessel occlusion (LVO) is sometimes necessary in patients with steno-occlusive disease of the extracranial internal carotid artery (ICA) or ICA dissection. Use of antiplatelet agents is required to prevent in-stent thrombosis; however, after an LVO, a decompressive hemicraniectomy may be necessary. After placement of a carotid stent, a fine balance must be obtained between preventing stent-related thromboembolic complications while also maintaining the possibility of quickly and safely performing a decompressive hemicraniectomy, if indicated. In this case, we discuss the novel use of continuous eptifibatide and cangrelor infusions after carotid stent placement to maintain stent patency, while preserving the option of emergent hemicraniectomy. A 55-year-old man presented with left hemispheric ischemic symptoms due to flow failure from a left ICA dissection. He underwent emergent angiography with angioplasty and stenting of the petrous and ascending cervical segments of the left ICA. The procedure was complicated by an embolization of thrombus to a left middle cerebral artery (MCA) M2 division branch, resulting in an occlusion, which could not be opened. The patient was placed on short acting intravenous antiplatelet agents (eptifibatide infusion for 60 h and cangrelor infusion for 24 h) for prevention of in-stent thrombosis while under close observation for potential neurologic decline and need for decompressive hemicraniectomy. After 84 h of observation, the patient did not experience a decline and the antiplatelet infusions were discontinued after he received aspirin and a loading dose of clopidogrel. Intravenous eptifibatide or cangrelor infusions are short-acting antiplatelet options that can be used in patients with acute ischemic stroke from LVO in the setting of ICA stent placement when there exists a potential for decompressive hemicraniectomy. J Neurol Res. 2020;10(3):99-103 doi: https://doi.org/10.14740/jnr591

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

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. 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. In all, 18 original research reports and case reports/series were included in the review. 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. 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.

Do We Need Potent Intravenous Antiplatelet Inhibition at the Time of Reperfusion During ST-Segment Elevation Myocardial Infarction?

Acute myocardial infarction (MI) is still a large source of morbidity and mortality worldwide. Although early reperfusion therapy has been prioritized in the modern era of percutaneous coronary intervention and thrombolysis, attempts at incremental improvements in clinical outcomes by reducing MI size have not been successful so far. Herein, we review the studies that have evaluated immediate-onset antiplatelet therapy as attempts to improve meaningful clinical outcomes in ST-segment elevation MI (STEMI). Unfortunately, many of the adjunctive pharmacotherapies have proven to be disappointing. Recent studies performed in the background of routine oral administration of P2Y12 adenosine receptor inhibitors, which may take several hours to take full effect, and aspirin have largely shown no improvement in outcomes, despite an earlier onset of antiplatelet activity of the investigative agents. Further progress in improving outcomes during STEMI may depend on exploring therapeutics that modulate the pathophysiology of microvascular damage during ischemia-reperfusion injury, a phenomenon whose effects evolve over hours to days. We speculate that the dynamic nature of the no-reflow phenomenon may be an explanation for these disappointing results with the intravenous antiplatelet agents. We hope that appreciation for what has not worked in this domain may direct future research efforts to focus on novel pathways. Myocardial ischemia and reperfusion injury are very much still a lingering issue. Despite significant improvements in door-to-balloon times, rates of in-hospital mortality for STEMI remain unchanged. Outcomes following successfully reperfused STEMI are likely determined by the initial size of myocardial necrosis (ie, cardiomyocyte death during the period of ongoing ischemia), patency of the infarct-related epicardial coronary artery, possible reperfusion injury, the microvascular no-reflow phenomenon, and adverse remodeling after infarction.

Safety and preliminary efficacy of intravenous tirofiban in acute ischemic stroke patient without arterial occlusion on neurovascular imaging studies

BackgroundThere has been no effective treatment for acute ischemic stroke (AIS) patients who presented to the Emergency Department >4.5h without a visible arterial occlusion on the neurovascular imaging studies. In this study, we aimed to investigate whether intravenous antiplatelet agent tirofiban was safe and potentially effective in AIS patients who had no visible arterial occlusion and was outside of treatment window for Alteplase. The goal of this study was to collect preliminary data to plan a future phase II study. MethodTwenty-five patients received intravenous tirofiban therapy. The safety outcomes were assessed by the incidence of symptomatic intracerebral hemorrhage (sICH), systematic bleeding and mortality. Efficacy outcomes were evaluated with National Institutes of Health Stroke Scale (NIHSS) score at day 7 (or discharge) and modified Rankin Scale (mRS) at 90days. Outcomes for these patients were compared with a historical age-gender-admission-NIHSS matched cohort treated with aspirin and/or clopidogrel. ResultsThe rate of intracerebral hemorrhage, systematic bleedings, and death were not found in both groups. At day 7 or discharge, the neurological function improved significantly in both treatment groups. However, the NIHSS score was lower in tirofiban group compared with the control group (2 vs.3, p=0.045). At 3months, more patients in tirofiban group had favorable outcomes (mRS 0–1) compared with control group (84% vs. 52%; adjusted odds ratio: 10.57; 95% CI: 1.54–72.33; p=0.016). ConclusionsIntravenous tirofiban appears to be safe and potentially effective for the ischemic stroke patients with no artery occlusion on neurovascular imaging studies and being out of the window for thrombolytic therapy. A next logic step is to plan for a phase II study.

Bridging with Tirofiban during Oral Antiplatelet Interruption: A Single-Center Case Series Analysis Including Patients on Hemodialysis.

Patients requiring an interruption in dual-antiplatelet therapy (DAPT) within 6 months of cardiac stenting are at risk for thrombotic events. Bridging with short-acting intravenous antiplatelet agents has been proposed to minimize the risk of thrombotic and hemorrhagic complications. This retrospective analysis of a tirofiban bridging strategy did not use an initial bolus loading dose. Tirofiban infusions were initiated 24-48 hours after the last oral antiplatelet dose at a rate of 0.1 μg/kg/min (or 0.05 μg/kg/min if renal dysfunction) and continued until 4-8 hours before surgery or until DAPT could be resumed. Coprimary end points were occurrence of major adverse cardiac events (MACE) and bleeding. Twenty patients requiring DAPT interruption within 6 months of cardiac stenting for either a surgical procedure or who were unable to take any medications by mouth were included. The median time from stent implantation to DAPT interruption was 33 days (range 3-146 days). Two patients experienced a MACE during their hospital stay. No major bleeding events occurred; minor bleeding occurred in four patients during tirofiban therapy. Five patients in this analysis had end-stage renal disease requiring hemodialysis. Of these patients, no MACE or major bleeding events occurred. This analysis observed that a tirofiban bridging strategy without an initial bolus loading dose has comparable efficacy and safety as previously published reports. A tirofiban infusion without bolus dosing may be a safe option for antiplatelet bridging in patients with a recent cardiac stent implant to prevent stent thrombosis.

Clinical pathways and management of antithrombotic therapy in patients with acute coronary syndrome (ACS): a Consensus Document from the Italian Association of Hospital Cardiologists (ANMCO), Italian Society of Cardiology (SIC), Italian Society of Emergency Medicine (SIMEU) and Italian Society of Interventional Cardiology (SICI-GISE).

Antiplatelet therapy is the cornerstone of the pharmacologic management of patients with acute coronary syndrome (ACS). Over the last years, several studies have evaluated old and new oral or intravenous antiplatelet agents in ACS patients. In particular, research was focused on assessing superiority of two novel platelet ADP P2Y12 receptor antagonists (i.e., prasugrel and ticagrelor) over clopidogrel. Several large randomized controlled trials have been undertaken in this setting and a wide variety of prespecified and post-hoc analyses are available that evaluated the potential benefits of novel antiplatelet therapies in different subsets of patients with ACS. The aim of this document is to review recent data on the use of current antiplatelet agents for in-hospital treatment of ACS patients. In addition, in order to overcome increasing clinical challenges and implement effective therapeutic interventions, this document identifies all potential specific care pathway for ACS patients and accordingly proposes individualized therapeutic options.

Abstract TP320: Efficacy and Safety of Antiplatelet Therapy for Ischemic Stroke without Large Arterial Occlusion by Intravenous Tirofiban

Introduction: All over the world, Each year twelve million people develop ischemic stroke and 30-40% of them do not have visible arterial occlusions at presentation. Hypothesis: In this study, we aim to investigate whether intravenous antiplatelet agent tirofiban in acute ischemic stroke(AIS) patients without large arterial occlusion(LAO) is effect or safe. Material and methods: We performed an open-label study to collect data of patients without LAO and without thrombolytic therapy within 24 hours from the symptom onset.These patients were divided into 2 groups: those who received tirofiban(tirofiban group) and those who did not received tirofiban(control group).The safety endpoint was the incidence of symptomatic intracranial hemorrhage(SICH) within 72 hours. The efficacy outcome measure was the National Institutes of Health Stroke Scale (NIHSS) score improvement at 24 hours and 7 days and modified Rankin Scale (mRS) score ≤1 or return to baseline mRS at 90 days. Results: Of 105 subjects, 53 received Intravenous tirofiban and 52 did not receive it. No patients in our trial had SICH. At 90 days, 67.9%(36/53)of the tirofiban group had mRS ≤1 or return to baseline mRS versus 53.8%(28/52)in control group(P=0.032). At 24 hour in the hospital, the NIHSS score improvement was significantly higer in the tirofiban group compared with control group(p=0.004). At hospital day 7 or hospital discharge, the NIHSS score improved significantly in the tirofiban group compared with the control group (p=0.009). Conclusions: This study provided data that patients with ischemic stroke who did not have LAO and not receive thrombolysis therapy may benefit from Intravenous Tirofiban.

Dual antiplatelet therapy and non-cardiac surgery: evolving issues and anesthetic implications

Dual antiplatelet therapy (DAPT) consisting of aspirin plus a P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor) is imperative for the treatment of acute coronary syndrome, particularly during the re-endothelialization period after percutaneous coronary intervention (PCI). When patients undergo surgery during this period, the consequences of stent thrombosis are far more serious than those of bleeding complications, except in cases of intracranial surgery. The recommendations for perioperative DAPT have changed with emerging evidence regarding the improved efficacy of non-first-generation drug (everolimus, zotarolimus)-eluting stents (DES). The mandatory interval of 1 year for elective surgery after DES implantation was shortened to 6 months (3 months if surgery cannot be further delayed). After this period, it is generally recommended that the P2Y12 inhibitor be stopped for the amount of time necessary for platelet function recovery (clopidogrel 5–7 days, prasugrel 7–10 days, ticagrelor 3–5 days), and that aspirin be continued during the perioperative period. In emergent or urgent surgeries that cannot be delayed beyond the recommended period after PCI, proceeding to surgery with continued DAPT should be considered. For intracranial procedures or other selected surgeries in which increased bleeding risk may also be fatal, cessation of DAPT (possibly with continuation or minimized interruption [3–4 days] of aspirin) with bridge therapy using short-acting, reversible intravenous antiplatelet agents such as cangrelor (P2Y12 inhibitor) or glycoprotein IIb/IIIa inhibitors (tirofiban, eptifibatide) may be contemplated. Such a critical decision should be individually tailored based on consensus among the anesthesiologist, cardiologist, surgeon, and patient to minimize both ischemic and bleeding risks.