Bivalirudin for unsalvageable venous congestion or obstruction in head and neck free flap reconstruction.

Microvascular free flap surgery permits single-stage reconstruction of complex head and neck ablative defects. Venous congestion can occur in the early postoperative period, risking partial or total flap loss. While prompt surgical re-exploration is often required, a number of adjunct medical treatments have been explored. Recently, there has been an anecdotal rise in the use of the anticoagulant bivalirudin, a recombinant derivative of hirudin. However, there has only been one case series report on the use of bivalirudin in head and neck free flap venous congestion. Here, we describe our team's experience with bivalirudin through a series of 7 patients.

Bivalirudin as an anticoagulation strategy for acute hemodialysis in children: Two cases with a summary of recent literature.

Unfractionated heparin is the most used anticoagulative agent for extracorporeal settings in children, including acute hemodialysis modalities. In certain situations, such as heparin-induced thrombocytopenia, alternatives must be applied. The direct thrombin inhibitor bivalirudin has come forth as an attractive substitute. Bivalirudin is currently only approved for adult use in specific percutaneous coronary intervention settings. However, it has a growing off-label popularity in different contexts for both adult and pediatric patients. Experience with bivalirudin in children is mainly limited to extracorporeal membrane oxygenation, ventricular assist devices and during cardiopulmonary bypass surgery. Literature about its use as anticoagulation strategy for pediatric hemodialysis is very scarce. Here, we present two pediatric cases where bivalirudin was used during acute hemodialysis, followed by a short summary of recent literature.

Bivalirudin versus heparin in patients with or without bail-out GPI use: a pre-specified subgroup analysis from the BRIGHT-4 trial.

BACKGROUND: Conflicting results comparing bivalirudin versus heparin anticoagulation in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), in part due to the confounding effect of glycoprotein IIb/IIIa inhibitors (GPI). The aim of the study was to compare the safety and effectiveness of bivalirudin plus a post-PCI high-dose infusion vs heparin with or without bail-out GPI use. METHODS: We conducted a pre-specified subgroup analysis from the BRIGHT-4 trial that randomized 6016 STEMI patients who underwent primary PCI to receive either bivalirudin plus a post-PCI high-dose infusion for 2-4 h or heparin monotherapy. GPI use was only reserved as bail-out therapy for procedural thrombotic complications. The primary outcome was a composite of all-cause death or Bleeding Academic Research Consortium (BARC) types 3-5 bleeding at 30 days. RESULTS: A total of 5250 (87.4%) patients received treatment without GPI while 758 (12.6%) received bail-out GPI. Bail-out GPI use was associated with an increased risk of the primary outcome compared to non-GPI use (5.28% vs. 3.41%; adjusted hazard ratio (aHR), 1.62; 95% confidence interval (CI), 1.13-2.33; P = 0.009) and all-cause death (5.01% vs. 3.12%; aHR, 1.74; 95% CI, 1.20-2.52; P = 0.004) but not in the risk of BARC types 3-5 bleeding (0.53% vs. 0.48%; aHR, 0.90; 95% CI, 0.31-2.66; P = 0.85). Among patients without GPI use, bivalirudin was associated with lower rates of the primary outcome (2.63% vs. 4.21%; aHR, 0.55; 95% CI, 0.39-0.77; P = 0.0005), all-cause death (2.52% vs. 3.74%; aHR, 0.58; 95% CI, 0.41-0.83; P = 0.003), and BARC types 3-5 bleeding (0.15% vs. 0.81%; aHR, 0.19; 95% CI, 0.06-0.57; P = 0.003) compared with heparin. However, among patients requiring bail-out GPI, there were no significant differences observed in the rates of the primary outcome (5.76% vs. 4.87%; aHR, 0.77; 95% CI, 0.36-1.66; P = 0.50; Pinteraction = 0.07) or its individual components between bivalirudin and heparin groups. CONCLUSIONS: Bivalirudin plus a post-PCI high-dose infusion was associated with significantly reduced 30-day composite rate of all-cause death or BARC types 3-5 bleeding compared with heparin monotherapy in STEMI patients undergoing primary PCI without GPI use. However, these benefits might be less pronounced in patients requiring bail-out GPI due to thrombotic complications during primary PCI. TRIAL REGISTRATION: ClinicalTrials.gov NCT03822975.

Effect of bivalirudin on myocardial microcirculation and adverse events after interventional therapy in older patients with acute coronary syndrome.

BACKGROUND: Bivalirudin, a direct thrombin inhibitor, is used in anticoagulation therapies as a substitute for heparin, especially during cardiovascular procedures such as percutaneous coronary intervention. AIM: To explore the effect of bivalirudin on myocardial microcirculation following an intervention and its influence on adverse cardiac events in elderly patients with acute coronary syndrome (ACS). METHODS: In total, 165 patients diagnosed with acute myocardial at our hospital between June 2020 and June 2022 were enrolled in this study. From June 2020 to June 2022, elderly patients with ACS with complete data were selected and treated with interventional therapy. The study cohort was randomly divided into a study group (n = 80, administered bivalirudin) and a control group (n = 85, administered unfractionated heparin). Over a 6-mo follow-up period, differences in emergency processing times, including coronary intervention, cardiac function indicators, occurrence of cardiovascular events, and recurrence rates, were analyzed. RESULTS: Significant differences were observed between the study cohorts, with the observation group showing shorter emergency process times across all stages: Emergency classification; diagnostic testing; implementation of coronary intervention; and conclusion of emergency treatment (P < 0.05). Furthermore, the left ventricular ejection fraction in the observation group was significantly higher (P < 0.05), and the creatine kinase-MB and New York Heart Association scores were notably lower than those in the control group (P < 0.05). CONCLUSION: In elderly patients receiving interventional therapy for ACS, bivalirudin administration led to increased activated clotting time achievement rates, enhanced myocardial reperfusion, and reduced incidence of bleeding complications and adverse cardiac events.

Bivalirudin Versus Heparin Monotherapy in Patients with ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: A Study-level Meta-analysis of Randomized Controlled Trials.

AIMS: The present meta-analysis focused on investigating whether bivalirudin plus post-PCI infusion was safer and more effective than heparin monotherapy in patients who developed ST-segment elevation myocardial infarction (STEMI) and who underwent primary percutaneous coronary intervention (PCI). METHODS: The PubMed, EMBASE, Cochrane Library, and Web of Science databases were systemically searched to identify randomized controlled trials (RCTs) comparing bivalirudin and heparin for treating STEMI patients who underwent primary PCI. The Cochrane quality assessment tool was used to assess the quality of the enrolled studies. The primary and secondary outcomes included net adverse clinical events (NACEs, comprising all-cause death or major bleeding), major adverse cardiovascular events (MACEs, comprising all-cause death, stroke, MI, and TVR), in-stent thrombosis (IST), and bleeding of Bleeding Academic Research Consortium (BARC) types 2, 3, and 5. RESULTS: The four RCTs, comprising 10,695 events, included 5350 patients who received bivalirudin combined with post-PCI infusion and 5345 patients who received heparin monotherapy. Compared with those in the heparin group, the number of NACEs (RR 0.84, 95% CI 0.73-0.96, P = 0.009), MACEs (RR 0.82, 95% CI 0.67-0.99, P = 0.04), and ISTs (RR 0.66, 95% CI 0.49-0.91, P < 0.0001) in the bivalirudin group was significantly lower. There were no significant differences in all-cause death, cardiac death, stroke, MI, TVR, or BARC type 2, 3, or 5 bleeding between the two groups. CONCLUSION: In STEMI patients undergoing primary PCI, bivalirudin plus post-PCI infusion significantly reduced the incidence of NACEs, MACEs, and ISTs compared with heparin monotherapy, without increasing the risk of MI or TVR. Bivalirudin may also contribute to a potential reduction in stroke, death, and BARC type 2, 3, and 5 bleeding rates.

Bivalirudin versus heparin in ST and non-ST-segment elevation myocardial infarction-Outcomes at two years.

BACKGROUND: The registry-based randomized VALIDATE-SWEDEHEART trial (NCT02311231) compared bivalirudin vs. heparin in patients undergoing percutaneous coronary intervention (PCI) for myocardial infarction (MI). It showed no difference in the composite primary endpoint of death, MI, or major bleeding at 180 days. Here, we report outcomes at two years. METHODS: Analysis of primary and secondary endpoints at two years of follow-up was prespecified in the study protocol. We report the study results for the extended follow-up time here. RESULTS: In total, 6006 patients were enrolled, 3005 with ST-segment elevation MI (STEMI) and 3001 with Non-STEMI (NSTEMI), representing 70 % of all eligible patients with these diagnoses during the study. The primary endpoint occurred in 14.0 % (421 of 3004) in the bivalirudin group compared with 14.3 % (429 of 3002) in the heparin group (hazard ratio [HR] 0.97; 95 % confidence interval [CI], 0.85-1.11; P = 0.70) at one year and in 16.7 % (503 of 3004) compared with 17.1 % (514 of 3002), (HR 0.97; 95 % CI, 0.96-1.10; P = 0.66) at two years. The results were consistent in patients with STEMI and NSTEMI and across major subgroups. CONCLUSIONS: Until the two-year follow-up, there were no differences in endpoints between patients with MI undergoing PCI and allocated to bivalirudin compared with those allocated to heparin. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02311231.

Anticoagulation during extracorporeal membrane oxygenation: A narrative review.

Extracorporeal Membrane Oxygenation (ECMO) is a technology that offers organ support for critically ill patients with respiratory and/or cardiac failure. Despite improvements in recent years in technology and the biocompatibility of circuits, patients on ECMO remain at high risk of hematologic complications, such as bleeding or thrombosis. Anticoagulation is required in most cases to limit the risk of clotting, but questions persist regarding the optimal anticoagulation strategy. More precisely, there is still debate around the best anticoagulation agent and monitoring tools as well as on the transfusion thresholds and appropriate corrective measures when faced with complications. This narrative review provides an overview of hemostasis on ECMO and the impact of circuit size and coating. The benefits and downsides of unfractionated heparin (UHF) and Direct Thrombin Inhibitors (DTIs) as anticoagulation agents are reviewed. Finally, commonly available coagulation tests (activated clotting time, activated partial thrombin time, anti-Xa, and viscoelastic tests) and their limitations are addressed. In conclusion, future research is needed to determine the best anticoagulation strategy for patients on ECMO.

Impact of inflammation and steroids on anti-coagulation in children supported on a ventricular assist device.

Critically ill pediatric patients supported on ventricular assist devices (VADs) are increasingly being anticoagulated on bivalirudin, but with difficulty monitoring anticoagulation. Activated partial thromboplastin time (aPTT) has recently been shown to poorly correlate with bivalirudin plasma concentrations, while dTT had excellent correlation. However, aPTT is the more common monitoring test and dTT testing is rarely used. In addition, effects of frequent clinical VAD scenarios (such as inflammation) on the accuracy of aPTT and dTT testing remains uncertain. We reviewed the effects of clinical scenarios (infection/inflammation, chylothorax, and steroids administration) on anticoagulation monitoring in 10 pediatric VAD patients less than 3 years at Cincinnati Children's Hospital Medical Center from 10/27/2020 to 5/6/2022 using bivalirudin for anticoagulation. There were 16 inflammation/infection, 3 chylothorax, and 6 steroids events. Correlation between dTT and aPTT was significantly lower after infection/inflammation, with dTT increasing prior to inflammation/infection while aPTT remained unchanged. In addition, steroids are administered to VAD patients to reduce inflammation and thus additionally stabilize anticoagulation. However, this anticoagulation stabilization effect was reflected more accurately by dTT compared to aPTT. In children requiring VAD support utilizing bivalirudin anticoagulation, inflammation/infection is a common occurrence resulting in anticoagulation changes that may be more accurately reflected by dTT as opposed to aPTT.

Ticagrelor vs clopidogrel when coadministered with bivalirudin in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

Background: The optimal perioperative antithrombotic strategy for patients with acute coronary syndrome (ACS) during percutaneous coronary intervention (PCI) remains controversial. Objectives: To determine the safety and effectiveness of bivalirudin plus ticagrelor vs bivalirudin plus clopidogrel in patients with ACS undergoing PCI in the real world. Methods: Between March 2016 and March 2019, 7234 patients with ACS who had undergone PCI, received bivalirudin periprocedurally, and were prescribed ticagrelor or clopidogrel were enrolled in a single-center, all-comer, modern, retrospective cohort study. Incidence rates of 12-month ischemia (cardiac death, myocardial infarction, or stroke), all-cause death, Bleeding Academic Research Consortium (BARC) type 2,3,5 bleeding, and BARC type 3,5 bleeding were compared between different groups. Results: In total, 4960 patients received bivalirudin plus clopidogrel and 2274 patients received bivalirudin plus ticagrelor. Compared with bivalirudin plus clopidogrel, bivalirudin plus ticagrelor was associated with lower ischemic events (1.74% vs 2.84%; relative risk, 0.61; 95% CI, 0.41-0.91; P = .02) and stroke (0.05% vs 1.01%, P < .001) within 12 months after PCI without excessive risk of bleeding (BARC type 2,3,5 bleeding: 4.49% vs 3.76%, P = .22; BARC type 3,5 bleeding: 2.84% vs 2.02%, P = .08). The beneficial effects of bivalirudin plus ticagrelor were consistent among subgroups. Conclusion: As an initial treatment strategy, bivalirudin plus ticagrelor could reduce the 12-month risk of ischemic events compared with bivalirudin plus clopidogrel significantly without increasing the bleeding risk in ACS patients undergoing PCI.

Heparin-induced DRESS syndrome in a paediatric patient and successful anaesthetic management in cardiovascular bypass surgery: case report.

BACKGROUND: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome is a severe adverse drug reaction marked by delayed hypersensitivity reactions causing skin and systemic complications. DRESS diagnosis is challenging due to the variety of clinical presentations and symptom overlap with other conditions. The perioperative period in these patients requires precise pharmacological strategies to prevent complications associated with this syndrome. The treatment of DRESS induced by unfractionated heparin during cardiopulmonary bypass (CPB) surgery presents some challenges that must be considered when selecting an anticoagulant to avoid side effects. In this case, bivalirudin, a direct thrombin inhibitor, is indicated as an alternative to heparin in patients undergoing CPB. However, in contrast to heparin/protamine, there is no direct reversal agent for bivalirudin. CASE PRESENTATION: We report the case of an 11-year-old male diagnosed with native aortic valve endocarditis and thrombosis in his left lower extremity. During valvular replacement surgery, systemic unfractionated heparin was administered. Postoperatively, the patient developed fever, eosinophilia and pruritic rash. Warm shock and elevated alanine transaminase (ALT) and aspartate transaminase (AST) levels followed, leading to the diagnosis of DRESS syndrome. Treatment with methylprednisolone resulted in complete resolution of symptoms. Seven years later, the patient was readmitted due to insufficient anticoagulation and a thrombus in the prosthetic aortic valve, presenting a recurrent DRESS episode due to the administration of unfractionated heparin, which was later replaced with low-molecular-weight heparin during hospitalization. Treatment with corticosteroids and antihistamines was initiated, resulting in the resolution of this episode. Ultimately, the patient required the Ross procedure. During this intervention the anticoagulation strategy was modified, unfractionated heparin was replaced with bivalirudin during the procedure and fondaparinux was administered during the postoperative period. This resulted in stable transaminases levels and no eosinophilia. CONCLUSION: The severity of DRESS Syndrome underscores the importance of early recognition, heightened monitoring, and a comprehensive approach tailored to each patient's needs. This particular case highlights the significance of this approach and may have a substantial clinical impact since it provides alternatives to heparin, such as bivalirudin and fondaparinux, in the anticoagulation strategy of CPB for patients who have a hypersensibility reaction to this medication; thus, enhancing clinical outcomes by minimizing risks linked to adverse drug reactions.

Bivalirudin as a substitute for heparin in neurointervention for patients with heparin-induced thrombocytopenia.

OBJECTIVES: Heparin-induced thrombocytopenia is a known complication of heparin exposure with potentially life-threatening sequelae. Direct thrombin inhibitors can be substituted for heparin in patients with heparin-induced thrombocytopenia that require anticoagulation. However, the use of direct thrombin inhibitors as a substitute for heparin has not been widely reported in the neuroendovascular literature. MATERIALS AND METHODS: Here we report the first use of the direct thrombin inhibitor bivalirudin in a neuroendovascular procedure as a substitute for heparin in a patient with a ruptured pseudoaneurysm and heparin-induced thrombocytopenia, and review the literature on the use of bivalirudin and argatroban for such patients. RESULTS: Bivalirudin was safely and effectively used in the case reported, with no thrombotic or hemorrhagic complications. Our literature review revealed a paucity of studies on the use of heparin alternatives, including bivalirudin, in neuroendovascular procedures in patients with heparin-induced thrombocytopenia. CONCLUSIONS: Heparin-induced thrombocytopenia is an important iatrogenic disease process in patients undergoing neuroendovascular procedures, and developing protocols to diagnose and manage heparin-induced thrombocytopenia is important for healthcare systems. While further research needs to be done to establish the full range of anticoagulation options to substitute for heparin, our case indicates bivalirudin as a potential candidate.

Anticoagulation strategy with bivalirudin plus aspirin combination during extracorporeal membrane oxygenation for COVID-19-associated acute respiratory distress syndrome.

Background: In this study, we present our experience in treating patients receiving extracorporeal membrane oxygenation for novel coronavirus disease-2019 (COVID-19)-associated acute respiratory distress syndrome using a combined anticoagulant and antiaggregant treatment with intravenous infusion of bivalirudin and aspirin. Methods: Between April 1st, 2020 and January 31st, 2022, a total of 52 adult patients (32 males, 20 females; mean age: 44.5±11.5 years; range, 21 to 71 years) who received extracorporeal membrane oxygenation due to COVID-19-associated acute respiratory distress syndrome and whose anticoagulant treatment consisted of bivalirudin plus aspirin were retrospectively analyzed. During the first 10 days of extracorporeal membrane oxygenation, bivalirudin dosing, activated partial thromboplastin time, and activated clotting time, as well as major bleeding events and patient and/or ECMO-circuit thromboses were recorded. Results: The mean bivalirudin dose per day ranged from 0.03 to 0.04 mg/kg/h, with a mean overall dose of 0.036 mg/kg/h. The mean activated partial thromboplastin time was 49.1±6.9 sec throughout 10 days of the application. The percentage of time in the target range for activated partial thromboplastin time was 58.9±20.1% within 10 days of application, compared to 33.1±31.1% for the first 24 h. The mean daily activated clotting time was below the target range within the first three days, but it was consistently within the target range after Day 3. During the first 10 days of the application, no mortality occurred. Major bleeding occurred in 11 patients (21.1%) and circuit thrombosis occurred in three patients (5.8%). Conclusion: In patients receiving extracorporeal membrane oxygenation for COVID-19-associated acute respiratory distress syndrome, an hourly bivalirudin dose of 0.03 to 0.04 mg/kg/h throughout the first 10 days of application was associated with the targeted anticoagulation profile of 45 to 60 sec. The combination was associated with a comparable rate of major bleeding, but a lower rate of circuit-thrombosis compared to the literature reports.

Impact of Bivalirudin on Ischemia/Reperfusion Injury in Patients with Reperfused STEMI Assessed by Cardiac Magnetic Resonance.

Thrombin is an important ischemia/reperfusion injury (IRI) mediator in patients with ST-elevation myocardial infarction (STEMI). This study examines the use of bivalirudin, a direct thrombin inhibitor, in reducing IRI in STEMI patients. STEMI patients (n = 21) were treated with bivalirudin and compared to 21 patients treated with unfractionated heparin (UFH) from the EARLY Assessment of Myocardial Tissue Characteristics by CMR in STEMI (EARLY-MYO-CMR) registry (NCT03768453). Infarct size (IS) and left ventricular ejection fraction (LVEF) were comparable between the two groups at follow up. During the first cardiac magnetic resonance (CMR) scan within the first week after percutaneous coronary intervention (PCI), all patients in both the bivalirudin and UFH groups exhibited myocardial edema. However, the myocardium edema volume was significantly less in the bivalirudin group (p < 0.05). At the one-month follow-up, a smaller proportion of patients in the bivalirudin group than in the UFH group exhibited myocardial edema (4.7% vs. 33.3%, p < 0.05). At the three-month follow-up, myocardial edema had completely resolved in the bivalirudin group, while it persisted in two patients in the UFH group. The incidence and volume of microvascular obstruction (MVO) were significantly lower in the bivalirudin group during the acute phase. Additionally, the incidence of intramyocardial hemorrhage (IMH) was significantly lower in the bivalirudin group during both the acute and follow up (p < 0.05). These findings were corroborated by T2 and T1 mapping results. The study concluded that the use of bivalirudin for anticoagulation is associated with attenuated IRI in STEMI patients who receive primary PCI.

Complex management of pulmonary embolism in APLA syndrome: a case study of ECMO and bivalirudin utilization.

We report a case of a 22-year-old female with antiphospholipid antibody (APLA) syndrome who presented with severe dyspnea. Diagnostic imaging confirmed pulmonary embolism (PE), and treatment comprised unfractionated heparin and apixaban. APLA syndrome was diagnosed based on clinical, serological, and radiological findings. During evaluation, the patient developed cardiogenic shock necessitating catheter-directed thrombolysis, followed by veno-arterial extracorporeal membrane oxygenation (VA-ECMO) due to deteriorating condition and suspected heparin-induced thrombocytopenia (HIT). Surgical embolectomy with bivalirudin use followed, and a hybrid veno-arterial-venous (VAV) ECMO setup was implemented. Postoperatively, the patient improved, transitioning to veno-venous (VV) ECMO and eventually ECMO withdrawal. ECMO is a valuable tool for managing complex cardiorespiratory cases like PE. In the context of HIT and APLA syndrome, prompt anticoagulant transition is vital, and bivalirudin is an effective heparin alternative. Our study highlights the challenges involved in managing patients needing ECMO support with immunothrombotic conditions like HIT and APLA syndrome.

Use of bivalirudin after initial heparin management among adult patients on long-term venovenous extracorporeal support as a bridge to lung transplant: A case series.

A growing body of evidence supports the use of bivalirudin as an alternative to unfractionated heparin (UFH) for the prevention of thrombotic events in patients on venovenous (VV) extracorporeal membrane oxygenation (ECMO). However, data in patients bridged to lung transplantation are limited. In this case series, we describe the outcomes of six patients who were transitioned from UFH to bivalirudin during their course of VV ECMO support as a bridge to lung transplantation. All six patients were on VV ECMO support until transplant, with a median duration of 73 days. Bivalirudin demonstrated a shorter time to first therapeutic activated thromboplastin time (aPTT) level. Additionally, time in therapeutic range was longer while patients were receiving bivalirudin compared to UFH (median 92.9% vs. 74.6%). However, major bleeding and thrombotic events occurred while patients were receiving either anticoagulant. Based on our experience, bivalirudin appears to be a viable option for anticoagulation in VV ECMO patients bridged to lung transplantation. Larger studies evaluating the optimal anticoagulation strategy in patients bridged to transplant are needed.

Argatroban as an Add-On to rtPA in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

Current treatment options for acute ischemic stroke, including intravenous thrombolysis (IVT) and mechanical thrombectomy, have undoubtedly revolutionized stroke care. The need for additional treatment options has brought into the light direct thrombin inhibitors (DTIs) and, specifically, argatroban as a promising candidate. However, there is uncertainty regarding the safety of adding argatroban to IVT, mainly due to the increased hemorrhagic risk. In this study, we performed a systematic review and meta-analysis examining the safety and efficacy of argatroban as an add-on treatment for IVT. The following databases were searched from inception until the 14th of May 2023: Pubmed/MEDLINE, ClinicalTrials.gov, the EU Clinical Trials Register, EMBASE/Scopus, and the Cochrane Library. Only randomized clinical trials (RCTs) enrolling patients with acute ischemic stroke who underwent IVT evaluating the add-on use of any DTIs were selected for the systematic review and further meta-analysis. The PRISMA guidelines were followed at all stages. Four studies with argatroban were included in the final analysis. Analysis of risk ratio and relative risk shows that the add-on therapy with argatroban seems to be effective and favors a good clinical outcome (mRS 0-2) at 90 days, similar to that of alteplase. All studies showed a low pooled incidence of symptomatic intracerebral hemorrhage (5%), parenchymal hematoma (3%), and other major bleeding (1%). Argatroban as an add-on treatment to IVT seems not to be associated with excessive bleeding risk; however, its efficacy remains unproven. According to this synopsis of the currently available evidence, it is premature to use argatroban as an add-on to IVT treatment outside the current clinical trial setting.

Evaluation of Bivalirudin During Adult Extracorporeal Membrane Oxygenation: A Retrospective Characterization of Dosing, Efficacy and Bleeding.

Objective: Although heparin is the current standard anticoagulant during venoarterial (VA) and venovenous (VV) extracorporeal membrane oxygenation (ECMO), factors including heparin-induced thrombocytopenia, heparin resistance and drug shortages necessitate alternative anticoagulants such as direct thrombin inhibitors. The aim was to characterize dosing, safety, and efficacy of bivalirudin during ECMO support. Methods: This retrospective single-center study included 24 adults on ECMO support who received ≥6 hours of bivalirudin. The primary endpoint was dose to first therapeutic activated partial thromboplastin time (aPTT). Secondary endpoints included evaluating dosing between ECMO modes, incidence of bleeding and thrombotic events, and time in therapeutic range (TTR). Results: The dose at time of first therapeutic aPTT was bivalirudin 0.05 [0.05-0.1] mg/kg/hour. Bivalirudin dosing requirements were lower in VAECMO compared to VV-ECMO patients and were not impacted by continuous venovenous hemofiltration. Time to therapeutic aPTT was 5.5 [2-13] hours for VA-ECMO and 4.5 [2-8.6] hours for VV-ECMO patients. During any mode of ECMO TTR was 58.3% [39.6-73.1]. Thrombotic events occurred in 3 (13%) patients and major bleeding occurred in 12 (50%) patients. Conclusions: Our findings demonstrated variable bivalirudin dosing requirements based on mode of ECMO and dosing modifications may not be required during CVVH. Factors including mode of ECMO, indication for bivalirudin and concomitant antiplatelet therapy may impact hematologic events. Application of this data can assist with developing a bivalirudin ECMO protocol which provides less variability in initial dosing and TTR.

Bivalirudin versus Heparin on Net Adverse Clinical Events, Major Adverse Cardiac and Cerebral Events, and Bleeding in Elderly Chinese Patients Treated with Percutaneous Coronary Intervention.

Bivalirudin as an anticoagulant reduces bleeding after percutaneous coronary intervention (PCI), while its impact in elderly Chinese patients treated with PCI needs more evidence. This study aimed to compare the clinical outcomes between bivalirudin and heparin in elderly Chinese patients treated with PCI. This cohort study retrieved data of 1,286 elderly patients treated with PCI who used bivalirudin (bivalirudin group, N = 493) or heparin (heparin group, N = 793) as anticoagulants. Net adverse clinical events (NACEs) (primary endpoint), major adverse cardiac and cerebral events (MACCEs), bleeding, and major bleeding within 30 days after PCI treatment were recorded for analysis. Our study illustrated that NACEs (12.4% vs. 17.4%, P = 0.015), bleeding (6.7% vs. 12.1%, P = 0.002), and major bleeding (2.2% vs. 6.6%, P < 0.001) were fewer in bivalirudin group compared to heparin group. No difference was found in MACCEs (7.5% vs. 9.6%,P = 0.200), and incidences of all-cause mortality (P = 0.257), cardiac mortality (P = 0.504), recurrent myocardial infarction (P = 0.423), ischemia-driven revascularization (P = 0.509), and stroke (P = 0.467), between bivalirudin group and heparin group. According to univariate logistic regression analyses, bivalirudin (vs. heparin) correlated with fewer NACEs (P = 0.016), bleeding (P = 0.002), and major bleeding (P = 0.001) in elderly patients treated with PCI, but not MACCEs (P = 0.202). After adjustment, bivalirudin (vs. heparin) was an independent factor for fewer NACEs [odds ratio (OR): 0.619, P = 0.009], bleeding (OR: 0.499, P = 0.003), and major bleeding (OR: 0.342, P = 0.003) in these patients. In summary, bivalirudin achieves fewer NACEs, bleeding, and major bleeding, but not MACCEs, versus heparin in elderly patients treated with PCI, which is verified in the multivariate model.

Bivalirudin versus unfractionated heparin in patients with myocardial infarction undergoing percutaneous coronary intervention: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Bivalirudin is an alternative accepted therapy to unfractionated heparin for patients with myocardial infarction (MI) undergoing percutaneous coronary intervention (PCI). We aimed in this meta-analysis to compare bivalirudin versus unfractionated heparin in patients with MI undergoing PCI. METHODS: We have screened PubMed/MEDLINE, Cochrane Library, and ClinicalTrials.gov (inception through January 8th, 2023) for randomized controlled trials (RCTs) evaluating bivalirudin versus unfractionated heparin in patients with MI undergoing PCI. The DerSimonian and Laird method was used for estimation of tau2 to calculate the risk ratio (RR) and 95 % confidence interval (CI). RESULTS: Ten RCTs with a total of 40,069 participants were included in our analysis. Bivalirudin as compared with unfractionated heparin was associated with significant decrease in major bleeding (RR 0.64 [0.52 to 0.79]; p < 0.01; I2 = 69 %) and cardiovascular mortality (RR 0.79 [0.67 to 0.92]; p < 0.01; I2 = 0 %). There was no significant difference between bivalirudin and unfractionated heparin groups in terms of major adverse cardiovascular events (RR 1.02 [0.91 to 1.14]; p = 0.73; I2 = 52 %), all-cause mortality (RR 0.89 [0.77 to 1.04]; p = 0.15; I2 = 23 %), MI (RR 1.02 [0.87 to 1.19]; p = 0.80; I2 = 36 %), stent thrombosis (RR 1.12 [0.52 to 2.40]; p = 0.77; I2 = 82 %), or stroke (RR 0.97 [0.73 to 1.29]; p = 0.85; I2 = 0 %). CONCLUSION: Our meta-analysis suggests that bivalirudin compared with unfractionated heparin in patients with MI undergoing PCI was associated with lower rates of major bleeding and cardiovascular mortality without a significant difference in major adverse cardiovascular events, all-cause mortality, MI, stroke, or stent thrombosis.