bivalirudin and Shock--Cardiogenic

This study evaluated differences in efficacy and safety outcomes with bivalirudin compared with unfractionated heparin (UFH) in patients with cardiogenic shock requiring venoarterial extracorporeal membrane oxygenation (VA ECMO). We performed a retrospective study at an academic medical center that included patients greater than 18 years of age supported with VA ECMO due to cardiogenic shock from January 2009 to February 2021. The primary endpoint was ECMO-associated thrombotic events normalized to duration of ECMO support. Secondary safety endpoints included major bleeding (per ELSO criteria) and blood product administration. Overall, 143 patients were included in our analysis with 54 having received bivalirudin and 89 having received UFH. Median duration of ECMO support was 92 (interquartile range, 56-172) hours. ECMO-associated thrombotic events per ECMO day were significantly less among those that received bivalirudin ( P < 0.001). In adjusted regression, bivalirudin was independently associated with an increased time to thrombosis when compared with UFH (Exp[B] -3.8; 95% confidence interval, 1.7-8.8; P = 0.002). Patients receiving bivalirudin experienced less major bleeding events ( P = 0.02) with less total red blood cell and fresh frozen plasma administration ( P = 0.04 and P = 0.03, respectively). Bivalirudin is a safe and efficacious alternative to UFH in patients requiring VA ECMO for cardiogenic shock.

Topics: Antithrombins; Extracorporeal Membrane Oxygenation; Hemorrhage; Heparin; Humans; Retrospective Studies; Shock, Cardiogenic; Thrombosis

VA-ECMO is commonly used for patients in cardiogenic shock (CS) or refractory cardiac arrest (CA) undergoing PCI for ACS. In this setting at high risk of both thrombotic and hemorrhagic complications, optimal anti-thrombotic therapy remains ill-defined. We hypothesized that an anti-thrombotic therapy comprising a parenteral anticoagulant (bivalirudin) and a parenteral anti-platelet agent (cangrelor) may prove safe and effective in this scenario. From November 2019 to December 2021, 14 patients received at least one dose of cangrelor (starting dose: 0.125 μg/kg/min) plus bivalirudin, without background aspirin, in the context of PCI and VA-ECMO for ACS-related CS/CA, and were included in this study. Efficacy endpoint was occurrence of thrombotic events and safety endpoint was major bleeding occurrence. Median age was 58 years. The majority (64%) presented with refractory CA. A thrombotic event occurred in 14%, while major bleeding occurred in 21% patients. One patient experienced arterial thrombosis after VA-ECMO arterial cannula removal, another experienced ischemic cerebellar stroke without functional sequelae. Bleeding events were: 29% BARC 3a, 14% BARC 3b, and 7% BARC 5b. Overall in-hospital mortality was 50%. Cangrelor was continued for 5 (4-10) days; temporary discontinuation was necessary in 36%, either for VA-ECMO cannula removal or for bleeding events. A low dose of cangrelor, associated with standard-intensity anticoagulation with bivalirudin was a feasible anti-thrombotic strategy in patients undergoing PCI during VA-ECMO support for ACS-related CS/CA. Bleeding events rates outweighed thrombotic events rates in this critically-ill population, although the observed rates were lowest among available studies.

Topics: Extracorporeal Membrane Oxygenation; Hemorrhage; Humans; Middle Aged; Percutaneous Coronary Intervention; Retrospective Studies; Shock, Cardiogenic; Thrombosis; Treatment Outcome

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.

Topics: Anticoagulants; Heart-Assist Devices; Heparin; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; Retrospective Studies; Shock, Cardiogenic; Tissue Plasminogen Activator; Treatment Outcome

The best combination of access site and anticoagulant used during primary percutaneous coronary intervention (PCI) in patients presenting with ST segment elevation myocardial infarction is not known.. We conducted a retrospective cohort study of all patients >18 years of age who underwent primary PCI in 2 large regional ST segment elevation myocardial infarction centers in Massachusetts between 2012 and 2014. The cohort was divided into 3 groups: bival/fem, hep/rad, or off-protocol, based on anticoagulation and access used. We used multiple logistic regression model to compare major cardiovascular events-major adverse cardiovascular events (MACE) and bleeding complications between the 2 on-protocol groups (bival/fem and hep/rad).. Of the 1074 patients in this study, there were 443 (41%), 501 (47%), and 130 (12%) patients in bival/fem, hep/rad, and off-protocol groups, respectively. There were significantly higher number of cardiogenic shock patients in the bival/fem compared to the hep/rad group (6.5% vs. 3.0%, P < 0.001). There was a trend toward reduced MACE in the hep/rad group compared to bival/fem (2.8 % vs. 5.1%, P = 0.068). When cardiogenic shock patients are excluded, there is no significant difference in mortality rates (bival/fem: 2.7% vs. hep/rad: 1.0%, P = 0.07) or bleeding complications between the groups (hep/rad: 4.5% vs. bival/fem: 2.1%, P = 0.06).. In patients undergoing primary PCI, there was a trend toward reduced inpatient MACE with the use of heparin and radial access compared with bivalirudin with femoral access. In patients without cardiogenic shock, there is no significant difference in mortality or bleeding rates between the 2 groups.

Topics: Antithrombins; Catheterization, Peripheral; Female; Femoral Artery; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; Male; Massachusetts; Middle Aged; Outcome and Process Assessment, Health Care; Peptide Fragments; Percutaneous Coronary Intervention; Radial Artery; Recombinant Proteins; Retrospective Studies; Shock, Cardiogenic; ST Elevation Myocardial Infarction

Bivalirudin is a direct thrombin inhibitor that is increasingly used in patients undergoing mechanical circulatory support as it presents many advantages compared with unfractionated heparin. The aim of this study was to describe our experience with bivalirudin as primary anticoagulant in patients undergoing ventricular assist device (VAD) implantation. An observational study was performed on 12 consecutive patients undergoing VAD implantation at our institution. Patients received a continuous infusion of bivalirudin, with a starting dose of 0.025 mg/kg/h; the target activated partial thromboplastin time (aPTT) was between 45 and 60 s. Patients never received heparin during hospitalization nor had a prior diagnosis of heparin-induced thrombocytopenia (HIT). All patients received a continuous flow pump except one. Preoperative platelets count was 134 000 ± 64 000 platelets/mm(3) . Mean bivalirudin dose was 0.040 ± 0.026 mg/kg/h over the course of therapy (5-12 days). Lowest platelets count during treatment was 73 000 ± 23 000 platelets/mm(3) . No thromboembolic complications occurred. Two episodes of minor bleeding from chest tubes that subsided after reduction or temporary suspension of bivalirudin infusion were observed. Intensive care unit stay was 8 (7-17) days, and hospital stay was 25 (21-33) days. Bivalirudin is a valuable option for anticoagulation in patients with a VAD and can be easily monitored with aPTT. The use of a bivalirudin-based anticoagulation strategy in the early postoperative period may overcome many limitations of heparin and, above all, the risk of HIT, which is higher in patients undergoing VAD implantation. Bivalirudin should no longer be regarded as a second-line therapy for anticoagulation in patients with VAD. [Correction added on 6 December 2013, after first online publication: The dose of bivalirudin in the Abstract to 0.025 mg/kg/h].

Topics: Aged; Anticoagulants; Cardiomyopathies; Female; Heart-Assist Devices; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Recombinant Proteins; Retrospective Studies; Shock, Cardiogenic; Treatment Outcome

Topics: Adrenal Insufficiency; Adrenergic alpha-Agonists; Adult; Anti-Inflammatory Agents; Antihypertensive Agents; Aspirin; Bisoprolol; Critical Illness; Epinephrine; Fibrinolytic Agents; Hirudins; Humans; Hydrocortisone; Male; Peptide Fragments; Piperazines; Prasugrel Hydrochloride; Ramipril; Recombinant Proteins; Shock, Cardiogenic; Thiophenes; Treatment Outcome

We sought to (1) determine the bleeding rates after primary percutaneous coronary intervention (PPCI) in our institution, where the default strategy has been transradial (TR) access in combination with unfractionated heparin (UFH) plus eptifibatide, and (2) compare these with the outcomes of patients treated with bivalirudin in HORIZONS-AMI.. HORIZONS-AMI demonstrated that in PPCI undertaken via the transfemoral route, routine use of bivalirudin was associated with lower bleeding rates and improved mortality compared to routine use of UFH plus glycoprotein IIb/IIIa inhibitor (GPI).. This was a single-center prospective registry of consecutive patients undergoing PPCI from January 2009 to August 2011 at the Queen Elizabeth Hospital Birmingham, UK. Thirty-day major bleeding was defined as per the HORIZONS-AMI criteria and also according to TIMI and GUSTO scales.. Of the 432 consecutive patients, 350 fulfilled entry criteria for HORIZONS-AMI. In contrast with HORIZONS-AMI, these subjects were older (62.5 ± 13.7 yr vs. 59.8 ± 11.1 yr, P < 0.05) with a higher rate of cardiogenic shock (6.3% vs. 0.8%, P < 0.0001). Despite this higher risk population, the rate of major bleeding was favorable (3.7% [95% CI: 2.0-6.3%] vs. 4.9% [4.0-6.1%], P = 0.32). Similarly, TIMI major bleeding (2.0% [0.8-4.1%] vs. 3.1% [2.3-3.4%], P = 0.10) and GUSTO severe or life-threatening bleeding (0.6% [0.1-2.5%] vs. 0.4% [0.2-0.9%], P = 0.75) were comparable.. Routine TR access for PPCI using UFH plus GPI is associated with a low 30-day rate of major bleeding equivalent to the bivalirudin arm of HORIZONS-AMI. Default transradial access for PPCI permits routine use of a GPI without the penalty of high bleeding rates.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Cardiac Catheterization; Coronary Thrombosis; England; Eptifibatide; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Peptides; Platelet Aggregation Inhibitors; Prospective Studies; Radial Artery; Recombinant Proteins; Registries; Risk Factors; Shock, Cardiogenic; Time Factors; Treatment Outcome

In patients undergoing percutaneous coronary intervention (PCI), clinical trials have demonstrated that the use of bivalirudin with provisional glycoprotein IIb/IIIa inhibitors is not inferior to heparin with systematic glycoprotein IIb/IIIa inhibitors on major adverse cardiac events and is associated with lower rates of bleeding in various clinical settings. Patients with cardiogenic shock (CS), however, have been excluded from all pivotal trials. A retrospective analysis of 86 consecutive patients undergoing PCI for acute myocardial infarction complicated by CS in our center from April 2003 to September 2007 was performed. In-hospital death, major adverse cardiac events, and bleeding rates were compared in 37 patients who received bivalirudin with or without glycoprotein IIb/IIIa inhibitors and 49 patients who were treated with heparin and glycoprotein IIb/IIIa inhibitors as anticoagulation management. Baseline demographic, clinical, and biological characteristics were similar in the 2 groups. The in-hospital death rate was significantly lower in the bivalirudin group (5.4 vs 32.7%, p = 0.002). There were no differences in the rate of major hematoma between the bivalirudin group and the heparin group (3 vs 2.6%, p = 0.46). In conclusion, bivalirudin with provisional use of glycoprotein IIb/IIIa inhibitors appears to be a safe and effective anticoagualtion strategy in patients undergoing primary PCI for acute myocardial infarction complicated by CS.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Angiography; Female; Follow-Up Studies; Heparin; Hirudins; Humans; Integrin beta3; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Platelet Membrane Glycoprotein IIb; Recombinant Proteins; Shock, Cardiogenic; Treatment Outcome

Bleeding and thrombus formation are common problems with life-threatening implications in patients receiving a left ventricular assist device. We describe the anticoagulation protocol for the 1st patient in the United States to undergo successful implantation of the HeartMate II left ventricular assist system.

Topics: Adult; Anticoagulants; Antithrombins; Dextrans; Drug Therapy, Combination; Follow-Up Studies; Heart-Assist Devices; Hirudins; Humans; Infusions, Intravenous; Male; Peptide Fragments; Prosthesis Implantation; Recombinant Proteins; Shock, Cardiogenic; Thromboembolism