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Objectives : The COVID-19 pandemic has been associated with cases of refractory acute respiratory distress syndrome (ARDS) sometimes requiring support with extracorporeal membrane oxygenation (ECMO). Bivalirudin can be used for anticoagulation in patients on ECMO support, but its efficacy and safety in patients with COVID-19 is unknown. We set out to compare the pharmacologic characteristics and dosing requirements of bivalirudin in patients requiring ECMO support for ARDS due to COVID-19 versus ARDS from other etiologies. Design and Setting : This retrospective case control study was performed at Indiana University Health Methodist Hospital in Indianapolis, IN. Participants : Patients were included if they were on veno-venous (VV) ECMO support between June 2019 and June 2020 and divided into two groups: ARDS secondary to COVID-19 and those with ARDS from another etiology (Non-COVID). Interventions : Patient demographics such as age, sex, weight, chronic comorbid conditions, baseline antiplatelet and anticoagulant use, antiplatelet use during ECMO, and need for renal replacement therapy were collected and compared between groups. Time to activated partial thromboplastin time (aPTT) goal, percentage of time at aPTT goal, bivalirudin rates, total bivalirudin requirements, total duration on bivalirudin, total duration on ECMO, mortality, and complications associated with ECMO were collected and compared between groups. Measurements and Main Results : A total of forty-two patients met inclusion criteria (n = 19 COVID-19, n = 23 Non-COVID). However, percentage of aPTTs at goal were maintained more consistently in patients with COVID-19 versus non-COVID (86% vs. 74%: p < 0.01). Higher median (IQR) daily rates (3.1 mCg/kg/min (2.3-5.2) vs. 2.4 mCg/kg/min (1.7-3.3): p = 0.05) and higher median (IQR) maximum rates of bivalirudin (5 mCg/kg/min (3.7-7.5) vs. 3.8 mCg/kg/min (2.5-5): p = 0.03) were required in the COVID-19 group versus the non-COVID group. Time to goal aPTT was similar between groups. There was no difference in complications associated with anticoagulation as demonstrated by similar rates of bleeding and thrombosis between both groups. Conclusions : Patients on ECMO with ARDS from COVID-19 require more bivalirudin overall and higher rates of bivalirudin to maintain goal aPTTs compared to patients without COVID-19. However, COVID-19 patients more consistently maintain goal aPTT. Future randomized trials are needed to support efficacy and safety of bivalirudin for anticoagulation of COVID-19 patients on ECMO.

BACKGROUND Bleeding is a common and costly complication of percutaneous coronary intervention (PCI). Bleeding avoidance strategies (BAS) are used paradoxically less in patients at high-risk of bleeding: "bleeding risk-treatment paradox" (RTP). We determined whether hospitals and physicians, who do not align BAS to PCI patients' bleeding risk (ie, exhibit a RTP) have higher bleeding rates. METHODS We examined 28,005 PCIs from the National Cardiovascular Data Registry CathPCI Registry for 7 hospitals comprising BJC HealthCare. BAS included transradial intervention, bivalirudin, and vascular closure devices. Patients' predicted bleeding risk was based on National Cardiovascular Data Registry CathPCI bleeding model and categorized as low (

Vaccine-induced thrombotic thrombocytopenia is a newly described disease process in the setting of expanding access to COVID-19 vaccination. The United States Centers for Disease Control and Prevention recommends treatment with an alternative to heparin in patients suspected of having vaccine-induced thrombotic thrombocytopenia. At this time there have been no reported outcomes from the treatment of vaccine-induced thrombotic thrombocytopenia with bivalirudin as a heparin alternative. We describe the early outcomes from the treatment of vaccine-induced thrombotic thrombocytopenia with bivalirudin as a heparin alternative. A 40-year-old Caucasian woman was found to have thrombocytopenia, cerebral venous sinus thrombosis, and pulmonary embolism following vaccination for COVID-19 with Ad26.COV2.S. She exhibited a steady rise in platelet count: 20×109/L at hospital day 0, 115×109/L at discharge on hospital day 6, and 182×109/L on outpatient follow-up on day 9. While the patient exhibited a transient drop in hemoglobin, there was no clinical evidence of bleeding. This patient did not demonstrate any clinical sequelae of thrombosis, and she reported resolution of her headache. Vaccination with Ad26.COV2.S appears to be associated with a small but significant risk for thrombotic thrombocytopenia within 13 days of receipt. The Centers for Disease Control and Prevention guidance to consider an alternative to heparin was not accompanied by specifically recommended alternatives. A single patient treated with bivalirudin for suspected vaccine-induced thrombotic thrombocytopenia subsequently experienced symptom improvement and a rise in platelet count and did not demonstrate any immediate negative outcomes. A provider may consider bivalirudin as an alternative to heparin in patients with suspected vaccine-induced thrombotic thrombocytopenia following Ad26.COV2.S vaccination, pending more definitive research.

Background Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse reaction to heparin. Patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) are routinely anticoagulated with heparin before the initiation of bypass. Heparin is contraindicated, however, in patients with acute HIT, and alternatives to routine practice are often used. While guidelines have recently been published addressing this topic 10, there remains variance between institutions in how these cases are treated. Our goal was to better delineate practice trends in the diagnosis and management of HIT patients requiring CPB. Methods We surveyed members of the Society of Cardiovascular Anesthesiologists (SCA) and the American Society for Extracorporeal Technology (AmSECT) using an online survey tool. Results We received 304 completed surveys (5.8% response rate), 75% completed by an anesthesiologist, and 24% by a perfusionist. The majority of respondents used clinical history and/or antibody testing (71% and 63%, respectively) to diagnose HIT. Seventy-five percent of respondents reported using an institutional protocol for HIT-CPB cases. Most respondents (89%) reported having at least 1 case in the last 3 years, with a total case experience of at least 785 cases (785 = the minimum number of cases in each case volume category × the number of respondents choosing that category). The strategy recommended in published guidelines, bivalirudin, was the most commonly reported alternative anticoagulation strategy (75%) used by respondents in HIT cases, with most (83%) using the activated clotting time (ACT) to monitor anticoagulation. Conclusions Most responding SCA and AmSECT members reported that their institution used a protocol or guideline for HIT/CPB cases, and most guidelines directed the use of bivalirudin as an alternative anticoagulant. Various other methods such as plasmapheresis are also being used with success in this patient population. Further research, including comparison studies of alternative anticoagulant strategies, is required to elucidate the best approach to these difficult cases.

Intravenous anticoagulation is standard of care in the treatment of ST-elevation myocardial infarction. Primary percutaneous coronary intervention is the most common reperfusion strategy. Four anticoagulant options are available: unfractionated heparin, enoxaparin, fondaparinux, and bivalirudin. This article discusses the mechanism of action and key pharmacodynamic characteristics of these agents. The evolution of outcomes with unfractionated heparin compared with bivalirudin in the changing landscape of contemporary percutaneous coronary intervention is chronicled. Current anticoagulation recommendations from practice guidelines are provided and unresolved issues including treatment of patient subsets such as women and chronic kidney disease are explored.

Objective: To determine and compare the incidence of in-hospital and 30-day hemorrhagic complication and major adverse cardiac events (MACEs) as evidence of safety and efficacy using three different anti- thrombotic strategies using Bivalirudin, Heparin plus Eptifibatide (GPI: GP IIb/IIIa inhibitor), and Unfractionated Heparin (UFH) monotherapy in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) in a tertiary care cardiac hospital. Background: UFH or Heparin plus Eptifibatide or Bivalirudin is the most commonly used antithrombotic regimen to improve peri and post-PCI clinical outcomes in a patient undergoing PCI for ACS. Among them, the most effective and optimal antithrombotic regimen for preventing ischemic complications while limiting bleeding risk in ACS patients undergoing PCI is still far from being clear. Methods: 324 ACS patients ( age >18 years and ≤75 years) who underwent PCI from May 2018 to May 2019 at UCC, BSMMU, Dhaka were consecutively enrolled in the study and were divided into three groups according to antithrombotic. The choice of Anti-thrombotic strategy was at the discretion of the operator(s) and the patient’s affordability. Group-A: 107 patients received Bivalirudin as intravenous (I/V) bolus of 0.75 mg/ kg, followed by an infusion of 1.75 mg/kg/hr up to 4 hours. Group-B: 111 patients received UFH as an I/ V bolus of 70-100 U/kg (targeted ACT: 250-300 s). Group-C: 106 patients were administered UFH plus Eptifibatide as per the standard hospital guidelines. Dual antiplatelet (DAPT) loading as Aspirin 300 mg plus P2Y12 inhibitors ( Clopidogrel 600 mg or Prasugrel 60 mg or Ticagrelor 180 mg) was given in all patients before the procedure. The maintenance dose of DAPT was continued for at least one month and patients were followed telephonically up to 30 days. The outcome measures were in-hospital and 30-day hemorrhagic complication and MACEs [death, MI, stroke, stent thrombosis and target-vessel revascularization (TVR)] Results: In-hospital outcome: Patients treated with Bivalirudin as compared with UFH had a significantly lower incidence of QMI lesions (0% vs.6%; p=0.038) and major bleeding (0% vs. 7%; p=0.021). The bleeding rate was also significantly lower in Bivalirudin arm as compared with Heparin plus GPI arm (0% vs. 6%; p=0.038). However, the incidence of cardiac death, stent thrombosis, TVR were no differences among the three groups. 30-day outcome: There was only one NQMI in the bivalirudin group as opposed to 8% in the heparin group (p=0.041). No other adverse effects were found significantly different among the study groups. Conclusion: In this perspective, observational study of ACS patients undergoing PCI in a single-center showed that Bivalirudin monotherapy is safer than other contemporary antithrombotic strategies. In terms of efficacy, Bivalirudin is non inferior to Heparin plus Eptifibatde but superior to UFH monotherapy. University Heart Journal Vol. 17, No. 2, Jul 2021; 91-98

Background: The effectiveness and safety of non-heparin anticoagulants for the treatment of heparin-induced thrombocytopenia (HIT) are not fully established, and the optimal treatment strategy is unknown. In a systematic review and meta-analysis, we aimed to determine precise rates of platelet recovery, new or progressive thromboembolism (TE), major bleeding, and death for all non-heparin anticoagulants and to study potential sources of variability. Methods: Following a detailed protocol (PROSPERO: CRD42020219027), EMBASE and Medline were searched for all studies reporting clinical outcomes of patients treated with non-heparin anticoagulants (argatroban, danaparoid, fondaparinux, direct oral anticoagulants [DOAC], bivalirudin, and other hirudins) for acute HIT. Proportions of patients with the outcomes of interest were pooled using a random-effects model for each drug. The influence of the patient population, the diagnostic test used, the study design, and the type of article was assessed. Findings: Out of 3’194 articles screened, 92 studies with 119 treatment groups describing 4’698 patients were included. The pooled rates of platelet recovery ranged from 74% (bivalirudin) to 99% (fondaparinux), TE from 1% (fondaparinux) to 7% (danaparoid), major bleeding from 1% (DOAC) to 14% (bivalirudin), and death from 7% (fondaparinux) to 19% (bivalirudin). Confidence intervals were mostly overlapping, and results were not influenced by patient population, diagnostic test used, study design, or type of article. Interpretation: Effectiveness and safety outcomes were similar among various anticoagulants, and significant factors affecting these outcomes were not identified. These findings support fondaparinux and DOACs as viable alternatives to conventional anticoagulants for treatment of acute HIT in clinical practice. Registration Information: PROSPERO: CRD42020219027. Funding Information: This study was supported by a research grant of the Swiss National Science Foundation (#179334). Declaration of Interests: Conflict-of-interest disclosure: M.N. received research grants from Bayer Healthcare. A.C. has served as a consultant for synergy and his institution has received research support on his behalf from alexion, Bayer, Novartis, novo Nordisk, Pfizer, Sanofi, spark, and Takeda. All other authors declare that no conflict of interest exists.

Purpose Bivalirudin as a thrombin inhibitor is proven to have a low risk of bleeding during percutaneous coronary intervention (PCI). Some evidence indicates comparable effectiveness and safety between bivalirudin and unfractionated heparin (UFH). Although bivalirudin during PCI offers more clinical and safety benefits to patients with chronic total occlusion (CTO), mostly via radial access, this has not been confirmed. The objective of this study was to examine the efficacy and safety of bivalirudin during percutaneous coronary intervention (PCI) in patients with CTO. Methods This trial used a retrospective cohort study design. Medical information from 736 patients with CTO who underwent PCI with bivalirudin or UFH at the First Affiliated Hospital of Zhengzhou University from July 2019 to September 2020 was extracted and analyzed. The primary end point was the 30-day incidence of net adverse clinical events (NACEs), and the secondary end point was the major adverse cardiovascular events (MACEs), which were related to safety and efficacy, respectively. Other end points incorporated each component of the primary outcome, target vessel revascularization, and stent thrombosis. Clinical and procedural characteristics at baseline were adjusted by using a logistic regression model. Findings Overall, 71.5% of patients with CTO used the radial approach. Both groups exhibited nonsignificant differences in the majority of baseline characteristics. The bivalirudin group was associated with a significant reduction in NACEs (12.9% vs 21.5%; P = 0.002) and major bleeding (2.5% vs 8.0%; P = 0.001) versus the UFH group at the end of the 30-day follow-up. The incidence of MACEs, myocardial infarction, death, stroke, stent thrombosis, and target vessel revascularization did not differ significantly between the 2 groups. Moreover, the bivalirudin group also reported a lower incidence of NACEs in the prespecified subgroups. Implications Bivalirudin exhibited comparative efficacy but superior safety compared with UFH among patients with CTO undergoing PCI. Chinese Clinical Trial Registry: ChiCTR2000034771.

© 2021 European Society of Cardiology. All rights reserved. Published by the Czech Society of Cardiology.

Acute kidney injury (AKI) is not uncommon in patients undergoing transcatheter aortic valve replacement (TAVR). We examined the incidence, predictors, and outcomes of AKI from the BRAVO 3 randomized trial. The BRAVO-3 trial included 802 patients undergoing transfemoral TAVR randomized to bivalirudin vs. unfractionated heparin (UFH). The primary endpoint of the trial was Bleeding Academic Research Consortium (BARC) type ≥ 3b bleeding at 48 h. Total follow-up was to 30 days. AKI was adjudicated using the modified RIFLE (Valve Academic Research Consortium, VARC 1) criteria through 30-day follow-up, and in a sensitivity analysis AKI was assessed at 7 days (modified VARC-2 criteria). We examined the incidence, predictors, and 30-day outcomes associated with diagnosis of AKI. We also examined the effect of procedural anticoagulant (bivalirudin or unfractionated heparin, UFH) on AKI within 48 h after TAVR. The trial population had a mean age of 82.3 ± 6.5 years including 48.8% women with mean EuroScore I 17.05 ± 10.3%. AKI occurred in 17.0% during 30-day follow-up and was associated with greater adjusted risk of 30-day death (13.0% vs. 3.5%, OR 5.84, 95% CI 2.62–12.99) and a trend for more BARC ≥ 3b bleeding (15.1% vs. 8.6%, OR 1.80, 95% CI 0.99–3.25). Predictors of 30-day AKI were baseline hemoglobin, body weight, and pre-existing coronary disease. AKI occurred in 10.7% at 7 days and was associated with significantly greater risk of 30-day death (OR 6.99, 95% CI 2.85–17.15). Independent predictors of AKI within 7 days included pre-existing coronary or cerebrovascular disease, chronic kidney disease (CKD), and transfusion which increased risk, whereas post-dilation was protective. The incidence of 48-h AKI was higher with bivalirudin compared to UFH in the intention to treat cohort (10.9% vs. 6.5%, p = 0.03), but not in the per-protocol assessment (10.7% vs. 7.1%, p = 0.08). In the BRAVO 3 trial, AKI occurred in 17% at 30 days and in 10.7% at 7 days. AKI was associated with a significantly greater adjusted risk for 30-day death. Multivariate predictors of AKI at 30 days included baseline hemoglobin, body weight, and prior coronary artery disease, and predictors at 7 days included pre-existing vascular disease, CKD, transfusion, and valve post-dilation. Bivalirudin was associated with greater AKI within 48 h in the intention to treat but not in the per-protocol analysis.

BACKGROUND The Berlin Heart EXCOR Pediatric (EXCOR) ventricular assist device (VAD) was introduced in North America nearly 2 decades ago. The EXCOR was approved under Humanitarian Device Exemption status in 2011 and received post-market approval (PMA) in 2017 from Food and Drug Administration. Since the initial approval, the field of pediatric mechanical circulatory support has changed, specifically with regard to available devices, anticoagulation strategies, and the types of patients supported. This report summarizes the outcomes of patients supported with EXCOR from the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) registry. These data were part of the PMA surveillance study (PSS) required by the Food and Drug Administration. METHODS ACTION is a learning collaborative of over 40 pediatric heart failure programs worldwide, which collects data for all VAD implantations as one of its initiatives. All patients in North America with EXCOR implants reported to ACTION from 2018 to 2020 ( n = 72) who had met an outcome were included in the EXCOR PSS group. This was compared with a historical, previously reported Berlin Heart EXCOR study group (Berlin Heart study [BHS] group, n = 320, 2007‒2014). RESULTS Patients in the PSS group were younger, were smaller in weight/body surface area, were more likely to have congenital heart disease , and were less likely to receive a bi-VAD than those in the BHS group. Patients in the PSS group were less likely to be in Interagency Registry for Mechanically Assisted Circulatory Support Profile 1 and were supported for a longer duration. The primary anticoagulation therapy for 92% of patients in the PSS group was bivalirudin . Success, defined as being transplanted, being weaned for recovery, or being alive on a device at 180 days after implantation, was 86% in the PSS group compared with 76% in the BHS group. Incidence of stroke was reduced by 44% and the frequency of pump exchange by 40% in the PSS group compared with those in the BHS group. Similarly, all other adverse events , including major bleeding, were reduced in the PSS group. CONCLUSIONS The PSS data, collected through ACTION, highlight the improvement in outcomes for patients supported with EXCOR compared with the outcomes in a historical cohort. These findings may be the result of changes in patient care practices over time and collaborative learning.

International journal of clinical pharmacy : IJCP 43(4), 825-838 (2021). doi:10.1007/s11096-021-01260-z, Published by Springer, Dordrecht [u.a.]

Objectives To compare current practices within the United States of anticoagulation management and blood transfusion in neonatal and pediatric extracorporeal membrane oxygenation patients with a 2013 international report. Design Cross-sectional survey distributed between August and December 2019. Setting Extracorporeal Life Support Organization-registered neonatal and pediatric extracorporeal membrane oxygenation centers in the United States. Participants Extracorporeal membrane oxygenation medical directors. Interventions None. Measurements and main results Eighty-three medical directors at 108 centers responded. After removing four duplicate responses, 79 surveys were analyzed. Seventy-nine percent (n = 62) report a written extracorporeal membrane oxygenation protocol for both anticoagulation and blood product management. Ninety-four percent (n = 74) report unfractionated heparin as their primary anticoagulant; the remaining use the direct thrombin inhibitor, bivalirudin. Ninety percent (n = 71) report measuring antifactor Xa levels. Most centers report using a combination of assays to monitor heparin therapy, either antifactor Xa and activated partial thromboplastin time (54%) or more commonly antifactor Xa and activated clotting time (68%). Forty-one percent use viscoelastic tests to aid management. Goal monitoring levels and interventions generated by out of range values are variable. Fifty-one percent will replace antithrombin. Platelet transfusion thresholds vary by age and center with ranges from 50,000 to 100,000 cells/µL. Eighty-two percent of respondents are willing to participate in a randomized controlled trial comparing anticoagulation strategies for patients receiving extracorporeal membrane oxygenation. Conclusions Compared with the 2013 pediatric population, extracorporeal membrane oxygenation center anticoagulation and blood transfusion approaches continue to vary widely. Most report continued use of heparin as their primary anticoagulant and follow a combination of monitoring assays with the majority using the antifactor Xa assay in their practices, a significant shift from prior results. Antithrombin activity levels and viscoelastic tests are followed by a growing number of centers. Platelet transfusion thresholds continue to vary widely. Future research is needed to establish optimal anticoagulation and blood transfusion management.

A recent heparin shortage related to an outbreak of African Swine Flu in China led to substantial increase in the use of direct thrombin inhibitors (DTI) as an alternative. We evaluated the safety and efficacy of DTIs by assessing the anticoagulation assays within the initial 48 h of therapy comparing before and during shortage. A retrospective evaluation of bivalirudin and argatroban was conducted at a single center before (May 24, 2018 through August 25, 2019) and during heparin shortage (August 26, 2019 through February 20, 2020). The primary outcome was time to first therapeutic activated partial thromboplastin time (aPTT). Secondary outcomes included the percentage of time in therapeutic aPTT range, in-hospital mortality, incidence of recurrent thrombosis, and hemorrhagic events. Of the 204 patients included in the study, 95 patients [bivalirudin (n = 35), argatroban (n = 60)] were included in the pre-shortage cohort and 109 patients [bivalirudin (n = 68), argatroban (n = 41)] were during shortage. No significant difference was observed in the time to first therapeutic aPTT pre- and during shortage (8.9 h ± 10.8 vs 8.8 h ± 10.2, P = 0.62). Compared to pre-shortage cohort, a greater percentage of time was spent in therapeutic aPTT range within the initial 48 h (32% (0–50) vs. 41.6% (0–63), P = 0.04) during shortage without statistically significant differences in the rates of in-hospital mortality, thrombosis, or bleeding. While the optimal DTI protocol is still be determined, the protocols presented in this study allowed for wide-spread utilization of DTIs during a critical heparin shortage without compromising patient safety and effectiveness, likely reflective of the enhancement of DTI protocols, clinician education, and multidisciplinary collaboration and guidance from pharmacy and hematology.

Background: Heparin-induced thrombocytopenia (HIT) is a rare autoimmune reaction that involves a decrease in platelet count following heparin exposure and can be associated with life-threatening thrombosis. Because of their prolonged heparin exposure, patients undergoing cardiac surgery are at risk of HIT, with an incidence of 0.1% to 3%. Case Report: A 65-year-old male with severe mitral regurgitation and preoperative ejection fraction of 20% to 25% underwent mitral valve bioprosthetic replacement with coronary artery bypass graft surgery. Heparin anticoagulation was started on postoperative day (POD) 1. Respiratory failure resulted in prolonged mechanical ventilation and heparinization without the ability to initiate warfarin. While the patient was on heparin, his platelet count declined on POD 2 and then steadily increased to above the preoperative level on POD 7. On POD 10, the patient's platelet count dramatically decreased, and on POD 13 he developed acute common femoral artery occlusion necessitating embolectomy. Intraoperative transesophageal echocardiography revealed heavy thrombus burden across the mitral bioprosthesis. HIT was confirmed with a positive heparin-induced platelet antibody and serotonin release assay. Heparin was stopped and argatroban initiated. The patient underwent reoperative bioprosthetic mitral valve replacement on POD 18 using bivalirudin intraoperatively. Despite resolution of HIT, the patient developed sepsis and died on POD 59. Conclusion: The diagnosis of HIT is challenging in patients who undergo cardiopulmonary bypass. Platelet counts often decrease 40% to 60% during the first 72 hours postoperatively, and the frequency of nonspecific anti–platelet factor 4/heparin antibody formation is high. These findings can mask early signs of HIT and delay diagnosis.

Introduction and objectives Patients who are vulnerable to hemodynamic or electrical disorders (VP) are often excluded from clinical trials and data on the optimal access-site or antithrombotic treatment are limited. We assessed outcomes of transradial vs transfemoral access and bivalirudin vs unfractionated heparin (UFH) in VP with acute coronary syndrome undergoing invasive management. Methods The MATRIX trial randomized 8404 patients to radial or femoral access and 7213 patients to bivalirudin or UFH. Among them, 934 (11.1%) were deemed VP due to advanced Killip class (n = 808), cardiac arrest (n = 168), or both (n = 42). The 30-day coprimary outcomes were major adverse cardiovascular and cerebrovascular events (MACE: death, myocardial infarction, or stroke) and net adverse clinical events (NACE: MACE or major bleeding). Results MACE and NACE were similarly reduced with radial vs femoral access in VP and non-VP. Transradial access was also associated with consistent relative benefits in all-cause and cardiovascular mortality or Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding with greater absolute benefits in VP. The effects of bivalirudin vs UFH on MACE and NACE were consistent in VP and non-VP. Bivalirudin was associated with lower all-cause and cardiovascular mortality in VP but not in non-VP, with borderline interaction testing. Bivalirudin reduced bleeding in both VP and non-VP with a larger absolute benefit in VP. Conclusions In acute coronary syndrome patients undergoing invasive management, the effects of randomized treatments were consistent in VP and non-VP, but absolute risk reduction with radial access and bivalirudin were greater in VP, with a 5- to 10-fold lower number needed to treat for benefits. Trial registry number: NCT01433627.

BACKGROUND Acute myocardial infarction (AMI) occurs when atherosclerotic lesions which present in the coronary arteries cause the intravascular plate to rupture and with the result of myocardial ischemia, hypoxia, and infarct. The preferred treatment for AMI is currently percutaneous coronary intervention (PCI), for which the key to the success is the choice of anticoagulant and thrombolytic drugs during surgery. Here, we aim to explore the effects of atorvastatin combined with bivalirudin on coagulation function, cardiac function, and inflammatory factors in elderly patients with AMI who underwent PCI. METHODS The clinical data of 86 AMI patients who were admitted to our hospital between February 2016 and May 2018 were retrospectively analyzed. Based on different treatments, the patients were divided into the control group and the observation group, with 43 patients in each group. The control group patients were treated with bivalirudin, and the observation group was treated with bivalirudin plus atorvastatin. Both groups of patients underwent PCI and the clinical efficacy, coagulation function, cardiac function, inflammatory factor levels and cardiovascular events (MACE), and other clinical data were compared between the groups. RESULTS The total clinical effective rate in the observation group was significantly higher than that in the control group (90.90% vs. 72.09%) (P

Coronary angiography and percutaneous coronary intervention (PCI) represent the recommended revascularization strategy for patients presenting with acute coronary syndrome (ACS). However, periprocedural bleeding events, of which up to 50% are related to the access site, remain an important complication of PCI and are associated with higher costs, prolonged hospital stays, and increased mortality. Several randomized trials have demonstrated that PCI performed via radial artery (RA) access is associated with a reduction in bleeding events, and perhaps a reduction in mortality compared with femoral artery (FA) access. As a result, current practice guidelines from the European Society of Cardiology and the Canadian Cardiovascular Society recommend that RA be the default strategy for PCI in patients presenting with ACS. The recently published Safety and Efficacy of Femoral Access vs. Radial Access in ST-Segment Elevation Myocardial Infarction (SAFARI-STEMI) trial challenges the benefits of a default RA approach in a contemporary setting where additional bleeding-reduction strategies (i.e., avoidance of glycoprotein IIb/IIIa inhibitors, routine use of bivalirudin for procedural anticoagulation, and vascular closure devices) were employed. In order to better understand the evidence that has shaped the current recommendations, we present a review of the background studies and major randomized trials comparing RA with FA in patients presenting with ACS.

Ventricular assist devices (VADs) have become a mainstay of advanced heart failure therapy in pediatrics, with outcomes in adolescents that parallel the excellent outcomes in adults. Unfortunately, outcomes for younger children and infants remain suboptimal. This review discusses the patient and device specifics that contribute to this discrepant outcome, highlight current treatment strategies, and suggest areas for future improvement. The field of pediatric mechanical circulatory support (MCS) continues to be driven by advancements in patient selection, timing of VAD implantation, and patient management strategies particularly with regard to anticoagulation. The use of direct thrombin inhibitors, such as bivalirudin, and weight-based antiplatelet therapy has shown promise in reducing the incidence of bleeding and stroke. While the number of devices remains limited, providers continue to leverage current technology and novel cannulation strategies to support smaller and more complex patients. Despite the challenges of supporting infants and small children, it remains a hopeful time for the field of pediatric MCS. While individual centers may only care for small number of VAD patients, the ACTION learning network has sparked collaboration across the field broadly with rapid dissemination of best practices to all centers. This collaboration has led to many advances and holds promise for driving future advancements.

Introduction: Bivalirudin and heparin are the two most commonly used anticoagulants used during Percutaneous Coronary Intervention (PCI). The results of Randomized Controlled Trials (RCTs) comparing bivalirudin versus heparin monotherapy in the era of radial access are controversial, questioning the positive impact of bivalirudin on bleeding. The purpose of this systematic review is to summarize the results of RCTs comparing the efficacy and safety of bivalirudin versus heparin with or without Glycoprotein IIb/IIIa Inhibitors (GPI). Methods: This systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA statements for reporting systematic reviews. We searched the National Library of Medicine PubMed, Clinicaltrial.gov and the Cochrane Central Register of Controlled Trials to include clinical studies comparing bivalirudin with heparin in patients undergoing PCI. Sixteen studies met inclusion criteria and were reviewed for the summary. Findings: Several RCTs and meta-analyses have demonstrated the superiority of bivalirudin over heparin plus routine GPI use in terms of preventing bleeding complications but at the expense of increased risk of ischemic complications such as stent thrombosis. The hypothesis of post- PCI bivalirudin infusion to mitigate the risk of acute stent thrombosis has been tested in various RCTs with conflicting results. In comparison, heparin offers the advantage of having a reversible agent, of lower cost and reduced incidence of ischemic complications. Conclusion: Bivalirudin demonstrates its superiority over heparin plus GPI with better clinical outcomes in terms of less bleeding complications, thus making it as anticoagulation of choice particularly in patients at high risk of bleeding. Further studies are warranted for head to head comparison of bivalirudin to heparin monotherapy to establish an optimal heparin dosing regimen and post-PCI bivalirudin infusion to affirm its beneficial effect in reducing acute stent thrombosis.

The use of percutaneous ventricular assist devices (VADs) in the acute management of cardiogenic shock is becoming increasingly common. The Impella is a percutaneous VAD, which requires a heparin-containing purge solution to prevent thrombosis and maintain proper pump functionality. In this report, we describe two patients with heparin-induced thrombocytopenia (HIT) supported with an Impella using a bivalirudin-containing purge solution. Case 1 involved a 39-year-old man with cardiogenic shock, initially implanted with an intraaortic balloon pump, who developed HIT early in his hospital course. His worsening hemodynamics necessitated the placement of an Impella and later venoarterial extracorporeal membrane oxygenation until he eventually underwent durable left VAD implantation. Case 2 involved a 69-year-old man who had an Impella implanted for worsening cardiogenic shock. HIT was suspected shortly after device insertion, necessitating switching his anticoagulation to bivalirudin. He was successfully bridged directly to heart transplantation. Both patients' courses resulted in therapeutic anticoagulation without major bleeding or thrombotic events. These cases demonstrate the safe and effective use of bivalirudin-containing purge solutions for patients with confirmed HIT requiring temporary mechanical circulatory support with Impella.

Objectives We sought to evaluate the efficacy and safety of bivalirudin versus heparin in patients with coronary artery disease undergoing transradial artery coronary intervention (TRI). Background Bivalirudin and radial artery access are independently associated with improved cardiovascular outcomes. However, data supporting a strategy of combining both to achieve additive improvements in cardiovascular outcomes provide conflicting results. Methods A systematic search was performed to identify randomized controlled trials (RCTs) of bivalirudin, in which vascular access sites were reported. The primary outcome was net adverse clinical events (NACE) at 30 days. Secondary outcomes were long-term NACE, short-, and long-term major adverse cardiovascular events, all-cause mortality, myocardial infarction, unplanned revascularization, stent thrombosis, and major bleeding. Results We identified 10 RCTs, including 16,328 patients who underwent TRI (mean age 64.6 ± 15.7 years, 72.5% male). Bivalirudin use was associated with decreased 30-day NACE compared with heparin (6.3 vs. 7.4%; risk ratio [RR] = 0.87; 95% confidence interval [CI] = 0.76-0.99; p = .04; number needed to treat = 91). No significant interactions were observed based on clinical presentation, administration of P2Y12 inhibitors, or glycoprotein IIb/IIIa-receptor inhibitors (GPI) use. There were no significant differences between groups in any prespecified secondary outcomes. There was, however, a significant reduction of major bleeding in the bivalirudin group compared with heparin when used in combination with routine GPI (RR = 0.41; 95% CI = 0.19-0.90; p = .03). Conclusions Among patients undergoing TRI, use of bivalirudin was associated with significantly reduced 30-day NACE compared with heparin. There was no significant difference in long term NACE, ischemic, or bleeding events compared with heparin.

Anticoagulation in a neonate is a challenge and the availability of anticoagulant options is extremely limited. Here we describe the use of a direct thrombin inhibitor, bivalirudin, in a full-term neonate with symptomatic cerebral sinovenous thrombosis complicated by bilateral thalamic hemorrhagic stroke and intraventricular hemorrhage, who could not be effectively treated with sodium heparin due to heparin resistance (HR) and showed thrombosis regression after start of bivalirudin treatment, without worsening of the hemorrhage. While the use of bivalirudin in neonates has been previously described, the indication of cerebral sinovenous thrombosis and the setting of HR are unique.

Objective Despite growing expertise and wide application of venovenous extracorporeal membrane oxygenation (VV ECMO) treatment for acute respiratory distress syndrome (ARDS) of different origin and during pandemics (H1N1 Influenza A virus and SARS-CoV-2), large reports are few and pertain mostly to multicenter registries, and randomized trials are difficult to perform. The aim of this study was to report outcomes, trends, and innovations of VV ECMO treatment over the last 11 years. Design, Setting, and Participants Observational study on 142 patients treated at the IRCCS San Raffaele Hospital in Milan from June 2009 (year of the H1N1 pandemic) to May 2020 (SARS-CoV-2 pandemic). Interventions None. Measurements and Main Results The main causes of ARDS were H1N1 pneumonia in 36% of patients, bacterial pneumonia in 17%, and SARS-CoV-2 in 9%. Seventy-two percent of patients were centralized from remote hospitals, of whom 33% had implanted VV ECMO before transport. The most common cannulation strategy was the dual-lumen catheter cannulation system (55%), and anticoagulation was performed with bivalirudin in most patients (79%). Refractory hypoxia was treated with intravenous beta-blockers (64%), nitric oxide (20%), and pronation (8%). Almost one-third of patients (32%) were extubated while on ECMO. Forty-nine percent of patients were discharged from the intensive care unit, and hospital discharge was 46%; survival was lower in patients requiring VV ECMO for more than three weeks compared with shorter support duration (23% v 56%, p = 0.007). Anticoagulation with bivalirudin was associated with higher survival, compared with heparin (55% v 31%, p = 0.03), and lower thrombocytopenia incidence (69% v 35%, p = 0.003). Conclusion VV ECMO is the pivotal rescue treatment for refractory ARDS—timely treatment and optimal care are needed to optimize therapy, as duration of support is associated with outcome. Anticoagulation with bivalirudin may improve outcome.

A variety of antithrombotic drugs are used during percutaneous coronary interventions (PCIs). We aimed to investigate the practicability of the use of bivalirudin and GPIs in patients receiving PCI. We searched 7 of 629 relevant records from PubMed, the Cochrane Library, EMBASE, and Web of Science for randomised controlled trials. There were no significant differences in the rates of major adverse cardiac events (MACE) between bivalirudin plus GPI and heparin (all P > .05). Bivalirudin plus planned GPI was similar to bivalirudin monotherapy in terms of the risk of MACE (risk ratio [RR] = 1.07; 95% confidence interval [CI] = .91 − 1.27; P = .55). Bivalirudin plus provisional GPI was associated with lower bleeding risk (RR = .57; 95% CI = .47 − .69; P

Extracorporeal membrane oxygenation (ECMO) contributes to coagulopathy, necessitating systemic anticoagulation to prevent thrombosis. Traditionally, unfractionated heparin (UFH) has been the anticoagulant of choice, however, due to many inadequacies new evidence suggests benefit with the use of direct thrombin inhibitors. This retrospective cohort sought to evaluate the safety and efficacy of bivalirudin compared to UFH in ECMO patients. Primary endpoints included incidence of bleeding and thrombosis. Percent time in therapeutic range (TR), time to achieve TR and number of dose titrations required to maintain TR were calculated to assess efficacy of institutional protocols. Overall incidence of thrombosis was low, with one event in the bivalirudin group and no events in the UFH group. No difference was found in rates of bleeding between groups (6% vs. 10%, P = 0.44). Bivalirudin yielded higher percent time in TR (86% vs. 33%, P < 0.001), faster time to TR (2 vs. 18 hr, P < 0.001) and required fewer dose adjustments to maintain TR (2 vs. 11, P < 0.001) compared to UFH. These results suggest bivalirudin and UFH are associated with similar rates of bleeding and thrombosis in patients requiring ECMO support. Our results demonstrate the favorable pharmacokinetic profile of bivalirudin, and its ability to consistently maintain TR when compared to UFH.

Background Prevention of hemorrhagic complications has emerged as a priority in patients undergoing Percutaneous Coronary Intervention (PCI) in addition to suppressing thrombotic complications. This goal is challenging to achieve in diabetic Acute Coronary Syndrome (ACS) patients as Diabetes Mellitus (DM) itself is a prothrombotic state with more pronounced vascular injury response and have a worse outcome after PCI compared with non-diabetic patients. In patients with ACS, Bivalirudin has been shown to result in similar rates of composite ischemia as Heparin plus GPI (GP IIb /IIIa inhibitor), while significantly reducing major bleeding and has received class I recommendation for PCI by American College of Cardiology (ACC 2013). Whether Bivalirudin is safe and effective specially in diabetic ACS patients undergoing PCI, as compared with Heparin (UFH) monotherapy, is unknown. Purpose To determine and compare the incidence of in-hospital and 30-day hemorrhagic complications and major adverse cardiac events (MACEs) as evidence of safety and efficacy using Bivalirudin versus Heparin in diabetic ACS patients undergoing PCI. Methods 218 diabetic ACS patients (age>18 years and ≤75 years) who underwent PCI from May 2018 to April 2019 at University Cardiac Centre, BSM Medical University, Dhaka, Bangladesh were randomly assigned to have UFH or Bivalirudin. Before the guide wire crossed the lesion, 111 patients in the UFH group received a bolus of 70–100 U/kg (targeted activated clotting time, ACT: 200–250 s). 107 patients in the Bivalirudin group received a loading dose of 0.75 mg/kg, followed by an infusion of 1.75 mg/kg/h for up to 4 hours. Dual antiplatelet (DAPT) loading as Aspirin 300 mg plus P2Y12 inhibitors (Clopidogrel 600 mg or Prasugrel 60 mg or Ticagrelor 180 mg) was given in all patients before the procedure. The maintenance dose of DAPT was continued for at least one month and patients were followed telephonically up to 30 days. The outcome measures were in-hospital and 30-day hemorrhagic complications and MACEs [death, MI, target vessel revascularization (TVR) and stroke]. Results Patients treated with Bivalirudin compared with Heparin had a significantly lower in-hospital incidence of QMI (0% vs. 6%; p=0.03) and major bleeding (0% vs. 7%; p=0.02). However, the incidence of cardiac death, stent thrombosis, TVR were no differences between two groups (p>0.05). There was only one NQMI in the Bivalirudin group as opposed to 8% in the Heparin group in 30 days following stenting (p=0.04). Conclusion In diabetic ACS patients undergoing PCI, Bivalirudin is safe and effective as it reduces immediate and short-term hemorrhagic complications as well as MACEs as compared with Heparin. Funding Acknowledgement Type of funding sources: None.

Acute coronary artery disease represents the leading cause of death worldwide. Some studies have shown that coagulation disorders can play a protective role against ischemic heart disease, presumably due to hypocoagulable state and decrease thrombin formation. However, autopsy reports showed atherosclerotic lesions in some patients with hemophilia. Since the introduction of clotting factors and replacement therapies, the life expectancy of patients with coagulation disorders has increased significantly. As a result, the incidence of cardiovascular diseases became higher making their treatment more challenging. Door to balloon strategy applies in ST-elevation myocardial infarction (STEMI), and percutaneous coronary intervention should not be delayed. While in non-STEMI (NSTEMI) and unstable angina, a hematology consult is essential. Prophylactic coagulation factor replacement is crucial in these patients in order to avoid bleeding complications, but on the other hand, these factors were also associated with thrombotic complications. Historically, bare-metal stents were preferred over drug-eluting stents in view of the shorter duration of dual antiplatelets therapy (DAPT). Currently, some trials have demonstrated the safety of new-generation drug-eluting stents in patients with elevated bleeding risk, where DAPT use is limited to four weeks. The radial artery is the preferred access and was found to have less bleeding complications when compared to the femoral access. Anticoagulation with heparin is the safest in view of antidote availability and shorter half-life. Bivalirudin has also been used in some case reports, while GP2b3a inhibitors are usually avoided except in a high thrombus burden. Close peri procedural follow-up is important with patient education about symptoms of bleed. Carefully and individually tailored antithrombotic and factor replacement therapy is required to overcome these clinically challenging situations. Early screening for cardiovascular risk factors and considering early intervention and management might help to improve the general health status of this population and reduce morbidity.

Pediatric mechanical circulatory support (MCS) is considered a strategy for heart failure management as a bridge to recovery and transplantation or as a destination therapy. The final outcome is significantly impacted by the number of complications that may occur during MCS. Children on ventricular assist devices (VADs) and extracorporeal membrane oxygenation (ECMO) are at high risk for bleeding and thrombotic complications that are managed through anticoagulation. The first detailed guideline in pediatric VADs (Edmonton Anticoagulation and Platelet Inhibition Protocol) was based on conventional antithrombotic drugs, such as unfractionated heparin (UFH) and warfarin. UFH is the first-line anticoagulant in pediatric MCS, although its profile is not considered optimal in pediatric setting. The broad variation in heparin doses among children is associated with frequent occurrence of cerebrovascular accidents, bleeding, and thrombocytopenia. Direct thrombin inhibitors (DTIs) have been utilized as alternative strategies to heparin. Since 2018, bivalirudin has become the chosen anticoagulant in the long-term therapy of patients undergoing MCS implantation, according to the most recent protocols shared in North America. This article provides a review of the non-traditional anticoagulation strategies utilized in pediatric MCS, focusing on pharmacodynamics, indications, doses, and monitoring aspects of bivalirudin. Moreover, it exposes the efforts and the collaborations among different specialized centers, which are committed to an ongoing learning in order to minimize major complications in this special pediatric population. Further prospective trials regarding DTIs in a pediatric MCS setting are necessary and in specific well-designed randomized control trials between UFH and bivalirudin. To conclude, based on the reported literature, the clinical use of the bivalirudin in pediatric MCS seems to be a value added in controlling and maybe reducing thromboembolic complications. Further research is necessary to confirm all the results provided by this literature review.

Background: Stroke related to percutaneous coronary interventions (PCIs) is an infrequent complication, which can be potentially life-threatening and can lead to serious disability. Aims: This study aimed to assess the relationship between the type of coronary procedure and incidence of stroke, as well as its predictors. Methods: This retrospective analysis was performed on prospectively collected data gathered in the Polish National Registry of Percutaneous Coronary Interventions (ORPKI) between January 2014 and December 2019 and included 1 177 161 coronary procedures. Among them, 650 674 patients underwent isolated diagnostic coronary angiography (DCA), and 526 487 PCI. Stroke was diagnosed in 157 patients (0.013%), of which 100 (0.015%) happened during DCA and 57 (0.011%) during PCI. Multivariable logistic regression analysis was performed to separate predictors of stroke in patients undergoing coronary angiography and PCI. Results: The percentage of patients with periprocedural stroke was higher in the group treated with isolated DCA during the analyzed time. Among predictors of stroke in patients undergoing DCA, we confirmed prior stroke (P

The use of extracorporeal life support (ECLS) devices has significantly increased in the last decades. Despite medical and technological advancements, a main challenge in the ECLS field remains the complex interaction between the human body, blood, and artificial materials. Indeed, blood exposure to artificial surfaces generates an unbalanced activation of the coagulation cascade, leading to hemorrhagic and thrombotic events. Over time, several anticoagulation and coatings methods have been introduced to address this problem. This narrative review summarizes trends, advantages, and disadvantages of anticoagulation and coating methods used in the ECLS field. Evidence was collected through a PubMed search and reference scanning. A group of experts was convened to openly discuss the retrieved references. Clinical practice in ECLS is still based on the large use of unfractionated heparin and, as an alternative in case of contraindications, nafamostat mesilate, bivalirudin, and argatroban. Other anticoagulation methods are under investigation, but none is about to enter the clinical routine. From an engineering point of view, material modifications have focused on commercially available biomimetic and biopassive surfaces and on the development of endothelialized surfaces. Biocompatible and bio-hybrid materials not requiring combined systemic anticoagulation should be the future goal, but intense efforts are still required to fulfill this purpose.

Background Venous thromboembolism (VTE) is a common condition that may manifest as intermediate or high-risk pulmonary embolism (PE), requiring either primary or subsequent fibrinolytic therapy. In these cases, catheter-directed thrombolysis (CDT) has been shown to be beneficial. Case summary We present the case of a borderline obese but otherwise healthy 43-year-old male individual, who was admitted with acute intermediate- to high-risk PE requiring treatment with intravenous unfractionated heparin. After initial therapy failure, the patient received CDT, with subsequent clinical worsening, and a mixed result of imaging studies suggesting partial central worsening and partial peripheral improvement of the thrombotic burden and right ventricular (RV) function. After a multidisciplinary PE response team (PERT) consultation, the diagnosis of heparin-induced thrombocytopenia (HIT) with normal platelet levels was made. Therapy was changed to intravenous bivalirudin, with an excellent clinical response and complete recovery of RV function. The patient was discharged with oral rivaroxaban therapy, and on follow-up was otherwise well. Discussion Apparent failure of thrombolytic therapy for VTE warrants a clinical investigation into possible causes of a pro-thrombotic state. In this case, the diagnosis of HIT was surprising, especially due to only a mild decline in platelet levels that were well within normal range. We also acknowledge the significance of our PERT in the key diagnosis made in this case.

Background Early hepatic artery thrombosis (HAT) after liver transplantation is a serious complication that frequently results in graft loss and the need for retransplantation. Although studies have reported on various operative and endovascular treatment approaches, pharmacologic strategies for the prevention or management of HAT are not well defined. Patients with blood clotting disorders, those with a contraindication to heparin, and those who have previously developed HAT represent unique challenges in management. Methods We present the case of a 9-month-old male with a hypercoagulable state who developed early HAT after two liver transplants, despite the use of postoperative therapeutic heparin infusion. Results and conclusion The patient successfully underwent a third liver transplant using intraoperative and postoperative bivalirudin infusion, a direct thrombin inhibitor. Rotational thromboelastometry (ROTEM) was used to guide anticoagulation and blood product administration in the perioperative period. At 1.5 years post-transplant, the patient has good graft function with patent hepatic vasculature. This case demonstrates the innovative use of bivalirudin anticoagulant therapy and viscoelastic methodologies to improve outcomes in hypercoagulable liver transplant recipients.

Temporary mechanical circulatory support (tMCS) devices are used for the management of cardiogenic shock. The Impella 5.0 (Abiomed; Danvers, MA) (IMP5) is a commonly used, surgically implanted, tMCS device that requires systemic anticoagulation and purge solution to avoid pump failure. To avoid heparin-induced thrombocytopenia (HIT) from unfractionated heparin (UFH) use, our program has explored the utility of bivalirudin (BIV) for systemic anticoagulation in IMP5. This single center, retrospective study included patients supported on IMP5 with BIV based AC. The efficacy and safety end points were recovery, bridge to left ventricular assist device (LVAD), cardiac transplant (HTX), or death as well as clinically significant bleeding, incidence of Tissue Plasminogen Activator (tPA) use for suspected pump thrombosis, stroke, and device failure. There were 31 patients included, and 26 (84%) received BIV purge solutions. The median duration of IMP5 was 6 (IQR 4–10) days. Most patients were bridged to LVAD (39%, 12); 16% (5) were bridged to HTX, 16% (5) recovered, and 29% (9) died. One patient (3%) suffered from ischemic stroke and 12% (4) patients developed clinically significant bleeding. tPA was administered to 8 (26%) patients. Logistic regression analysis demonstrated that duration of IMP5 was a significant predictor of tPA use (OR 1.28; 95% Confidence Interval 1.04–1.56). There were no cases of pump failure. Our experience highlights the feasibility of utilizing BIV for routine AC use in IMP5.

We have successfully done off pump total arterial coronary surgery (CABG) using Bivalirudin in a patient awaiting liver transplantation....

In case of unexplained post‐PCI coronary thrombosis, a HIT should be always considered. A pragmatic approach with bivalirudin may be reasonable, even in absence of confirmed laboratory diagnosis.

Despite the seminal trials on radial versus femoral access for percutaneous coronary intervention (PCI) in ST elevation myocardial infarction (STEMI) showing reduced bleeding, major adverse cardiovascular events and mortality; these outcomes were attributed by some to low usage of bivalirudin and an unnecessarily higher dose of Heparin, combined with high usage of GP IIb/IIIa inhibitors, as well as to the use of larger bore catheters in the femoral groups. To prove the point, a study comparing TF with TR access was mooted( Lee et al., 2013) 3; with bivalirudin instead of heparin, preferably with use of potent oral anti-platelets instead of GP IIb/IIIa inhibitors; and femoral vascular closure devices, ostensibly, to assess outcomes based on ‘access-site alone’. With this intent, the SAFARI STEMI study was designed. In this article we discuss some of the major short-comings of this trial which raise significant questions on its results.

Aims The efficacy and safety of continued bivalirudin infusion after percutaneous coronary intervention (PCI) remains uncertain. We sought to investigate the association between post-PCI bivalirudin infusion and the risk of net adverse clinical events (NACE) at 30 days. Methods and results In the GLOBAL LEADERS study, all patients who received bivalirudin during PCI were categorized according to the use of bivalirudin infusion after the procedure. The primary endpoint of the present analysis was NACE [a composite of all-cause death, any stroke, any myocardial infarction, all revascularization, and bleeding assessed according to the Bleeding Academic Research Consortium (BARC) criteria Type 3 or 5] at 30 days. The key safety endpoint was BARC Type 3 or 5 bleeding and definite stent thrombosis. Of 15 968 patients, 13 870 underwent PCI with the use of bivalirudin. In total, 7148 patients received continued bivalirudin infusion after procedure, while 6722 patients received standard care. After propensity score covariate adjustment, the risk of NACE did not significantly differ between two treatments after PCI [continued bivalirudin infusion vs. no bivalirudin infusion: 3.2% vs. 3.1%, adjusted hazard ratio (aHR) 1.35, 95% confidence interval (CI) 0.99–1.84, P = 0.06] nor the BARC Type 3 or 5 bleeding (0.7% vs. 0.7%, aHR 0.89, 95% CI 0.44–1.79; P = 0.743) and definite stent thrombosis (0.5% vs. 0.3%, aHR 1.71, 95% CI 0.77–3.81, P = 0.189). However, continued bivalirudin infusion was associated with an increased risk of NACE and definite stent thrombosis in ST-elevation myocardial infarction (STEMI) patients. Conclusion In an all-comers population undergoing PCI, there was no significant difference in the risk of NACE at 30 days between continued bivalirudin infusion vs. no bivalirudin infusion after procedure but continued bivalirudin infusion was associated with a higher risk of NACE in STEMI patients when compared with no infusion.

Aims The impact of diabetes mellitus (DM) on clinical outcomes after transcatheter aortic valve replacement (TAVR) remains unclear. The aim of this study was to investigate the impact of DM on short-term clinical outcomes after TAVR in a large randomized trial population. Methods and results BRAVO-3 trial randomized 802 patients undergoing trans-femoral TAVR to procedural anticoagulation with bivalirudin or unfractionated heparin. The study population was divided according to the presence of DM, and further stratified according to the use of insulin. Net adverse cardiovascular outcomes (NACE – death, myocardial infarction (MI), stroke or major bleeding by Bleeding Academic Research Consortium (BARC) type 3b or above) was the primary outcome in-hospital and at 30-days. Of the total 802 randomized patients, 239 (30%) had DM at baseline, with 87 (36%) being treated with insulin. At 30-days, DM patients experienced numerically higher rates of net adverse cardiovascular events (16.3% vs. 14.4%, p = 0.48) and acute kidney injury (19.7% vs. 15.1%, p = 0.11), while non-DM (NDM) patients had numerically higher rates of cerebrovascular accidents (3.6% vs. 1.7%, p = 0.22). After multivariable adjustment, DM patients had higher odds of vascular complications at 30-days (OR 1.57, p = 0.03) and life-threatening bleeding both in-hospital (OR 1.50, p = 0.046) and at 30-days (OR 1.50, p = 0.03) with the excess overall risk primarily attributed to the higher rates observed among non-insulin dependent DM patients. Conclusions Patients with DM had higher adjusted odds of vascular and bleeding complications up to 30-days post-TAVR. Overall, there was no significant association between DM and early mortality following TAVR.

Background Bivalirudin, a direct thrombin inhibitor, is a treatment option for the management of heparin-induced thrombocytopenia (HIT) and other coagulation disorders. To date, no published studies have identified patients at risk for or the consequence of subtherapeutic bivalirudin therapy. Objectives The primary objective was to identify factors associated with failure to achieve early therapeutic anticoagulation (ETA) with bivalirudin, defined as achievement of two consecutive therapeutic activated partial thromboplastin times (aPTTs) within 24 hours. Secondary objectives included evaluating whether failure to achieve ETA was a risk factor for clinical outcomes of interest including thromboembolism, hemorrhage, and mortality. Patients/methods This was a retrospective cohort study. Patients between the ages of 18 and 89 years treated with bivalirudin for 24 hours or longer were identified and classified as either achieving or failing to achieve ETA. Results Nonadherence to the dosing protocol (odds ratio [OR] 1.7, 95% confidence interval [CI] 1.07-2.71) and creatinine clearance (CrCl) of 60 ml/min or greater (OR 2.99, 95% CI 1.12-7.97) were significantly associated with failure to achieve ETA in univariate analyses. Conversely, increasing age (OR 0.98, 95% CI 0.97-0.99) was significantly associated with achievement of ETA. Failure to achieve ETA was associated with a 4-fold increase in the odds of thromboembolism. Conclusions Younger age, normal renal function, and nonadherence to the dosing protocol when targeting therapeutic anticoagulation is associated with increased risk of failure to achieve ETA. This confers an elevated risk of thromboembolism when using bivalirudin for the management of HIT or other coagulation disorders.

Use of extracorporeal membrane oxygenation to support patients with critical cardiorespiratory illness is increasing. Systemic anticoagulation is an essential element in the care of extracorporeal membrane oxygenation patients. While unfractionated heparin is the most commonly used agent, unfractionated heparin is associated with several unique complications that can be catastrophic in critically ill patients, including heparin-induced thrombocytopenia and acquired antithrombin deficiency. These complications can result in thrombotic events and subtherapeutic anticoagulation. Direct thrombin inhibitors (DTIs) are emerging as alternative anticoagulants in patients supported by extracorporeal membrane oxygenation. Increasing evidence supports DTIs use as safe and effective in extracorporeal membrane oxygenation patients with and without heparin-induced thrombocytopenia. This review outlines the pharmacology, dosing strategies and available protocols, monitoring parameters, and special use considerations for all available DTIs in extracorporeal membrane oxygenation patients. The advantages and disadvantages of DTIs in extracorporeal membrane oxygenation relative to unfractionated heparin will be described.

Background: The aim of the study was to compare the efficacy and safety of bivalirudin versus unfractionated heparin (UFH) in patients with acute myocardial infarction who undergo percutaneous coronary intervention (PCI). Earlier trials comparing bivalirudin and UFH during PCI demonstrated that bivalirudin caused less bleeding with more stent thrombosis. Since then, adjunct antiplatelet strategies have evolved. Improved upstream platelet inhibition with potent P2Y12 inhibitors decreased the need for routine glycoprotein IIb/IIIa inhibitor (GPI), resulting in similar outcomes among UFH and bivalirudin. Therefore, the role of bivalirudin in modern PCI practices is questionable. Methods: We utilized Cochrane Review Manager (RevMan) 5.3 to perform a meta-analysis of seven randomized controlled trials (RCTs) with 22,844 patients to compare bivalirudin to UFH in patients with acute myocardial infarction requiring revascularization. Results: There was no difference between bivalirudin and UFH regarding major adverse cardiac events (MACE), risk ratio (RR) 0.99, 95% confidence interval (CI) 0.87 - 1.12; P = 0.83) or cardiovascular mortality (RR 0.87, 95% CI 0.71 - 1.07; P = 0.18). Bivalirudin increased acute stent thrombosis (RR 2.77, 95% CI 1.49 - 5.13; P = 0.001), which was only significant among ST-elevation myocardial infarction (STEMI) only trials. Bivalirudin caused less major bleeding (RR 0.66, 95% CI 0.49 - 0.90; P = 0.007), which was negated when GPI was used provisionally (RR 0.93, 95% CI 0.64 - 1.33; P = 0.67). Conclusions: Among patients with acute myocardial infarction who underwent PCI, bivalirudin and UFH demonstrated similar MACE and cardiovascular mortality. Bivalirudin increased acute stent thrombosis, which was more remarkable among STEMI. Bivalirudin decreased major bleeding, but this benefit was negated when GPI was used provisionally. Cardiol Res. 2019;10(5):278-284 doi: https://doi.org/10.14740/cr921

Ventricular assist devices (VADs) are an increasingly common therapy for end-stage heart failure across all ages as a bridge to recovery or transplant and more recently as destination therapy. With increasing experience and difficulties with establishing therapeutic heparin levels, we have begun to explore the effectiveness of direct thrombin inhibitors in this patient population. This is a retrospective review of all long-term VAD patients, both adult and pediatric, who were anticoagulated with bivalirudin between January 2009 and January 2016. The starting dose was 0.3 mg/kg/hr, and dose was titrated for a goal partial thromboplastin time (PTT) of 70-100. There were 14 patients (13 males, 5 ≤18 years) with 17 episodes of bivalirudin therapy. The median age on initiation was 45 years (range, 15 days-67 years) with 10 episodes associated with a HeartWare HVAD, five a HeartMate II, and two with a Berlin Heart EXCOR. The predominant indication of bivalirudin therapy was suspected pump thrombosis (13/17). The median time from VAD insertion to initiation of bivalirudin was 116 days (range, 3-1,870) with the median duration of therapy being 21 days (range, 3-113). In patients with pump thrombosis, the mean baseline lactate dehydrogenase (LDH) was 229 ± 64 U/L, peak 690 ± 380 U/L, and decreased to 330 ± 243 U/L when bivalirudin was stopped. The outcomes following suspected pump thrombosis included: transitioned to warfarin (n = 7), death in two destination therapy patients who did not undergo pump exchange, transplantation (n = 2), and pump exchange (n = 2). A major bleeding complication occurred in only one patient. Our experience highlights the potential use of bivalirudin in a heterogenous VAD population. Although these initial results suggest some potential role for direct thrombin inhibitors for use in long-term VADs, larger prospective studies are required to support these preliminary observations and to determine who may benefit from direct thrombin inhibitors (DTIs) and the side effect profile in this patient population.

The parenterally administered direct thrombin inhibitors (DTIs) argatroban and bivalirudin are effective anticoagulants for acute heparin-induced thrombocytopenia (HIT) treatment. The activated partial thromboplastin time (aPTT) has classically been used as the monitoring test to assess degree of anticoagulation, however concerns exist with using aPTT to monitor DTI therapy. In this observational study plasma samples from DTI treated patients were analyzed by aPTT, dilute thrombin time (dTT) and ecarin chromogenic assay (ECA) to delineate results into concordant and discordant groups. Discordant samples were further analyzed via liquid chromatography with tandem mass spectrometry (LC MS/MS). In total 101 patients with 198 samples were evaluated. Discordance between tests were frequent (59% of DTI treated patients). Bivalirudin aPTT vs dTT discordance was observed in 45% (57/126) of samples. Amongst bivalirudin samples with test discordance dTT results were more likely to be concordant with LC MS/MS than the aPTT (77% vs 9%, p