bivalirudin and Heart-Failure

Extracorporeal membrane oxygenation (ECMO) offers therapeutic options in refractory respiratory and/or cardiac failure. Systemic anticoagulation with heparin is routinely administered. However, in patients with heparin-induced thrombocytopenia or heparin resistance, the direct thrombin inhibitor bivalirudin is a valid option and has been increasingly used for ECMO anticoagulation. We aimed at evaluating its safety and its optimal dosing for ECMO.. Systematic web-based literature search of PubMed and EMBASE performed via National Health Service Library Evidence and manually, updated until January 30, 2016.. The search revealed 8 publications relevant to the topic (5 case reports). In total, 58 patients (24 pediatrics) were reported (18 received heparin as control groups). Bivalirudin was used with or without loading dose, followed by infusion at different ranges (lowest 0.1-0.2 mg/kg/h without loading dose; highest 0.5 mg/kg/h after loading dose). The strategies for monitoring anticoagulation and optimal targets were dissimilar (activated partial thromboplastin time 45-60 seconds to 42-88 seconds; activated clotting time 180-200 seconds to 200-220 seconds; thromboelastography in 1 study).. Bivalirudin loading dose was not always used; infusion range and anticoagulation targets were different. In this systematic review, we discuss the reasons for this variability. Larger studies are needed to establish the optimal approach with the use of bivalirudin for ECMO.

Topics: Adult; Anticoagulants; Antithrombins; Child; Extracorporeal Membrane Oxygenation; Heart Failure; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; Respiratory Insufficiency; Thrombocytopenia; Thrombolytic Therapy

Available options for the treatment of advanced heart failure have expanded to include the use of mechanical circulatory assist devices to improve quality of life in those both eligible and ineligible for heart transplant. Although there have been significant advancements in device technologies, anticoagulation protocols, and multidisciplinary team management, bleeding and thrombosis are the most common adverse effects. Management strategies for pump thrombosis and their outcomes vary considerably among mechanical circulatory support centers and include intensification of antithrombotic therapy (medical) and device exchange (surgical). We describe a successful case of medical therapy for pump thrombosis with bivalirudin monotherapy.

Topics: Antithrombins; Extracorporeal Circulation; Heart Failure; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; Thrombosis

Heparin-induced thrombocytopenia (HIT) requires alternative anticoagulation strategies. We investigated outcomes in patients with HIT antibodies undergoing low-dose bivalirudin anticoagulation during left ventricular assist device implantation on an extracorporeal life support system (ECLS) and compared the results with non-HIT patients treated with heparin and receiving left ventricular assist device implantation with ECLS support.. The institutional ventricular assist device database was searched for the period from March 2012 to March 2016. The primary end-point was the need for early (<7 days) surgical re-exploration due to persistent haemorrhage or cardiac tamponade postoperatively. The secondary clinical end-points were delayed chest closure, stroke, intracranial bleeding, re-thoracotomy >7 days and mortality up to 1 year. Unadjusted comparison was used for the entire groups. Because of non-random group assignment, propensity score matching was also performed to compare treatment effects.. Twenty-one patients were treated with bivalirudin and 36 patients with heparin. INTERMACS levels were lower, inotropic score was higher and the prevalence of mechanical ventilation and preoperative ECLS implants was also significantly higher in the heparin group than in the bivalirudin group (P-values <0.05). The primary end-point was reached by 19% in the bivalirudin group and 16.7% in the heparin group (bivalirudin group: odds ratio 1.18, 95% confidence interval 0.29-4.76; P = 0.820). The propensity score-matched groups also showed no difference in this regard (P = 0.455). All secondary clinical end-points were comparable between groups, both in the unadjusted analysis and in the propensity score-matched groups.. In patients with HIT antibodies, low-dose bivalirudin anticoagulation on ECLS support appears to be a feasible option for left ventricular assist device implantation.

Topics: Antibodies; Anticoagulants; Antithrombins; Blood Coagulation; Extracorporeal Membrane Oxygenation; Female; Fibrinolytic Agents; Heart Failure; Heart-Assist Devices; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Recombinant Proteins; Retrospective Studies; Thrombocytopenia; Thrombolytic Therapy

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.

Topics: Adult; Aged; Antithrombins; Blood Coagulation; Child; Child, Preschool; Female; Heart Failure; Heart-Assist Devices; Hirudins; Humans; Infant, Newborn; Male; Middle Aged; Peptide Fragments; Recombinant Proteins; Retrospective Studies; Thrombosis; Treatment Outcome; Young Adult

Pump thrombosis is a serious left ventricular assist device complication, though there are no guidelines regarding its treatment. The main aim of this study was to describe a strategy of intravenous anticoagulation as the initial treatment in these patients and then to compare intravenous heparin with bivalirudin.. All consecutive patients who received a HeartWare left ventricular assist device from July 2009 to March 2019 were retrospectively analysed. Patients developing a pump thrombosis were selected, and treatment, outcomes and complications were recorded.. During this period of time (116 months), 220 patients underwent HeartWare left ventricular assist device implantation and 57 developed pump thrombosis, with an incidence rate of first pump thrombosis of 0.17 events per patient-year of support (incidence rate of all episodes of pump thrombosis: 0.30 events per patient-year of support). All the patients were initially treated medically, predominantly with either intravenous heparin (n = 26) or bivalirudin (n = 16). Patients treated with bivalirudin during the first pump thrombosis episode had less subsequent re-thrombosis episodes (18.7% vs 57.7%, p < 0.05). In addition, percentage time in therapeutic range was greater for bivalirudin compared with heparin (68.5% ± 16.9% vs 37.4% ± 31.0%, p < 0.01). During the first pump thrombosis episode, 26.3% of the patients needed surgery (left ventricular assist device exchange (n = 8), transplant (n = 6) or decommissioning (n = 1)). The overall survival at 1 year was 61.4%, and there was no significant difference in survival.. Left ventricular assist device thrombosis is a serious life-threatening complication; hence, we propose an initial conservative management of pump thrombosis with enhanced intravenous anticoagulation with either intravenous heparin or bivalirudin, with surgery reserved for refractory cases.

Topics: Adult; Antithrombins; Conservative Treatment; Female; Heart Failure; Heart-Assist Devices; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Recombinant Proteins; Retrospective Studies; Thrombosis

Outcomes with bivalirudin compare favorably with heparin ± GPIIb/IIIa receptor inhibition (heparin ± GPI) during percutaneous coronary intervention (PCI). Patients with congestive heart failure (CHF) have increased risk for complications. The objective was to investigate clinical and economic outcomes for bivalirudin ± GPI vs. heparin ± GPI among PCI patients with CHF.. Using the Premier Hospital Database, PCI patients with CHF were stratified by anticoagulant: bivalirudin, bivalirudin ± GPI, heparin and heparin ± GPI. The probability of receiving bivalirudin ± GPI was estimated using individual and hospital variables. Using propensity scores, each bivalirudin ± GPI patient was matched to a heparin ± GPI patient. The primary outcome was in-hospital death. Bleeding rates, transfusion, length of stay and in-hospital cost were ascertained.. Overall, 116,313 patients at 315 hospitals received bivalirudin (n = 45,559) bivalirudin + GPI (n = 8,115), heparin (n = 27,972) or heparin + GPI (n = 34,667). Patients had STEMI (21.2%), NSTEMI (29.1%), unstable angina (16.6%), stable angina (5.7%) or other ischemic heart disease (24.2%). Of these, 79.1% of bivalirudin patients matched, resulting in 84,948 analyzed patients. Compared with heparin ± GPI patients, bivalirudin ± GPI patients had fewer deaths (3.3% vs. 3.9%; p < 0.0001), less clinically apparent bleeding (10.2% vs. 11.4%; p < 0.0001), clinically apparent bleeding with transfusion (2.7% vs. 3.2%, p <0.0001), and transfusion (8.5% vs. 9.8%, p < 0.0001). Patients receiving bivalirudin had shorter length of stay (6.3 vs. 6.8 days; p < 0.0001) and lower in-hospital cost (mean $26,706 vs. $27,166 [median $19,414 vs. $19,798]; p < 0.0001). In conclusion, this is the largest retrospective analysis of PCI patients with CHF and demonstrates bivalirudin ± GPI compared with heparin ± GPI is associated with lower inpatient rates of death, bleeding, and cost.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Blood Loss, Surgical; Blood Transfusion; Cost-Benefit Analysis; Databases, Factual; Drug Costs; Female; Heart Failure; Heparin; Hirudins; Hospital Costs; Hospital Mortality; Humans; Length of Stay; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Recombinant Proteins; Retrospective Studies; Time Factors; Treatment Outcome; United States; Young Adult

The direct thrombin inhibitor bivalirudin is an option for anticoagulation in patients with heparin induced thrombocytopenia (HIT) requiring cardiopulmonary bypass (CPB). There are a limited number of reports of pediatric patients in which bivalirudin has been used for anticoagulation for CPB. We present the case of an 11 year old male with acute onset heart failure secondary to idiopathic dilated cardiomyopathy that developed heparin induced thrombocytopenia with thrombosis (HITT). The patient was anticoagulated in the operating room with bivalirudin and placed on CPB for insertion of a HeartWare(®) Ventricular Assist Device (Heartware(®)). Modified techniques were utilized. This included use of the Terumo CDI 500 (Terumo Cardiovascular Systems, Inc.) in-line blood gas monitor which contains a heparin coated arterial shunt sensor. We flushed this sensor with buffered saline preoperatively and noted no significant decrease in platelet count postoperatively. The patient was successfully placed on the ventricular assist device and was subsequently listed for heart transplantation.

Topics: Anticoagulants; Cardiomyopathy, Dilated; Cardiopulmonary Bypass; Child; Heart Failure; Heart Transplantation; Heart-Assist Devices; Heparin; Hirudins; Humans; Male; Peptide Fragments; Recombinant Proteins; Thrombocytopenia; Thrombosis

Patients with a previous history of heparin-induced thrombocytopenia are at a higher risk for thromboembolic events, and heparin administration is formally contraindicated. Bivalirudin has been reported as an alternative therapy whenever an intervention that requires systemic anticoagulation and cardiopulmonary by-pass pump is needed. We present the case of a patient diagnosed with heparin-induced thrombocytopenia and heparin-PF4 (+) antibodies requiring a triple cardiac valve replacement who developed fulminant coagulopathy after bivalirudin administration. A discussion on the serious difficulties that the management of these types of patients involves, as well as a review of prevention strategies are presented.

Topics: Acute Kidney Injury; Aged; Anticoagulants; Antithrombins; Blood Loss, Surgical; Coronary Artery Bypass; Disseminated Intravascular Coagulation; Drug Substitution; Fatal Outcome; Heart Failure; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Heparin; Hirudins; Humans; Immunoglobulin G; Intraoperative Complications; Male; Multiple Organ Failure; Peptide Fragments; Platelet Factor 4; Purpura, Thrombocytopenic, Idiopathic; Recombinant Proteins; Thrombophilia

In patients with acute heparin-induced thrombocytopenia (HIT) needing urgent cardiac surgery, bivalirudin is recommended as a first-line strategy for intraoperative anticoagulation. However, due to the unique elimination process of bivalirudin, careful adjustment of the perfusion and surgical strategy is mandatory as blood stasis in the circuit or prolonged interruption of areas or compartments containing blood from the systemic circulation may result in thrombus formation. We report here a modified surgical strategy for the implantation of the HeartWare™ left ventricular assist device, which avoids prolonged disconnection of the blood-filled device from the systemic blood flow, so that bivalirudin can be safely used as anticoagulant.

Topics: Anticoagulants; Blood Coagulation; Heart Failure; Heart-Assist Devices; Heparin; Hirudins; Humans; Peptide Fragments; Prosthesis Design; Prosthesis Implantation; Recombinant Proteins; Thrombocytopenia; Thrombosis; Treatment Outcome; Ventricular Function, Left

A patient with myocardial failure after repair of an acute type A aortic dissection had acute heparin-induced thrombocytopenia develop during extracorporeal membrane oxygenation. Heparin was discontinued and the anticoagulant was switched to the direct thrombin inhibitor bivalirudin given with a bolus of 0.5 mg/kg followed by a continuous infusion of 0.5 mg/kg/h. Using this protocol, activated clotting time values ranged from 200 to 220 seconds. After prolonged extracorporeal membrane oxygenation support and recovery of left ventricular function, a right ventricular assist device was implanted during extracorporeal membrane oxygenation support with bivalirudin anticoagulation. For this procedure an additional bolus of 0.25 mg/kg bivalirudin was given, and the infusion rate increased to 1 mg/kg/h to achieve activated clotting time values of 300 to 350 seconds. Surgery was successfully performed with moderate intraoperative and postoperative blood loss and transfusion requirements.

Topics: Adult; Anticoagulants; Aortic Aneurysm; Aortic Dissection; Cardiac Surgical Procedures; Extracorporeal Membrane Oxygenation; Female; Heart Failure; Heart-Assist Devices; Heparin; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; Thrombocytopenia

The Clinical Trials described in this article were presented at the Hotline and Clinical Trial Update Sessions of the European Society of Cardiology Congress held in September 2007 in Vienna, Austria. The sessions chosen for this article represent the scope of interest of Cardiovascular Drugs and Therapy. The presentations should be considered preliminary, as further analyses could alter the final publication of the results of these studies. PROSPECT evaluated echocardiographic criteria for optimal selection of patients with moderate to severe heart failure who may benefit from cardiac resynchronisation therapy, however concluded that no single echocardiographic measure can be recommended. EVEREST found that tolvaptan, a vasopressin V(2) antagonist, resulted in early weight reduction and improvement of dyspnoea in patients with acute heart failure, but lacked long term improvement. In ARISE, the anti-oxidant succinobucal did not affect the primary outcome in high risk cardiovascular patients, but improved the combination of cardiovascular death, myocardial infarction and stroke, and diabetic control in diabetics. ALOFT showed that the addition of the renin inhibitor aliskiren to an ACE inhibitor or ARB and a beta-blocker leads to favourable effects on neurohormonal actions in heart failure. FINESSE markedly improved coronary patency before PCI with half-dose reteplase/abciximab in STEMI patients, however without significantly improving short-term outcome. The Prague-8 Study evaluated whether routine clopidogrel administered >6 h pre-angiography would be a safe way to achieve therapeutic drug levels in case a follow-up intervention would be considered immediately, but appeared not justified because of bleeding complications. CARESS in MI showed that high risk patients with evolving STEMI who undergo thrombolytic therapy should undergo PCI early after the thrombolysis. Finally, the ACUITY trial found that in moderate or high risk Non ST elevation ACS patients triaged to PCI, coronary artery bypass graft (CABG) surgery, or medical management, bivalirudin, with or without associated GPIIb/IIIa inhibitor therapy, resulted in a marked reduction of bleeding at 30 days whilst preserving the ischemic and mortality benefit at 1 year follow up.

Topics: Abciximab; Acute Coronary Syndrome; Amides; Antibodies, Monoclonal; Benzazepines; Clinical Trials as Topic; Clopidogrel; Electrocardiography; Europe; Fumarates; Heart Diseases; Heart Failure; Hirudins; Humans; Immunoglobulin Fab Fragments; Myocardial Infarction; Peptide Fragments; Probucol; Recombinant Proteins; Ticlopidine; Tolvaptan

Unfractionated heparin has been a near universal anticoagulant for cardiac surgery; however it is contraindicated in heparin-induced thrombocytopenia type II. Alternative anticoagulants such as bivalirudin (a direct thrombin inhibitor) are being utilized. Bivalirudin was successfully used in an immunologically complex patient (diagnoses of heparin-induced thrombocytopenia type II, systemic lupus erythematosus, antiphospholipid syndrome, and dialysis-dependent renal failure) requiring cardiopulmonary bypass. Thrombotic events are common in antiphospholipid syndrome patients undergoing cardiac surgery utilizing high-dose heparin. This may represent unrecognized heparin-induced thrombocytopenia type II. Our patient did not experience perioperative thrombotic or bleeding complications. The possible cross-reactivity between heparin induced thrombocytopenia type II and antiphospholipid syndrome has not been investigated.

Topics: Adult; Antibody Specificity; Anticoagulants; Antiphospholipid Syndrome; Autoantibodies; Cross Reactions; Drug Evaluation; Drug Therapy, Combination; Female; Heart Failure; Heparin; Hirudins; Humans; Hypertension, Pulmonary; Kidney Failure, Chronic; Lupus Erythematosus, Systemic; Mitral Valve Insufficiency; Peptide Fragments; Platelet Count; Platelet Factor 4; Recombinant Proteins; Renal Dialysis; Thrombocytopenia; Thrombophilia; Warfarin

Heparin-induced thrombocytopenia (HIT) is an increasingly common clinical finding in patients presenting for cardiac transplantation. Bivalrudin, a reversible direct thrombin inhibitor, is a molecular anti-coagulant with short half-life and the potential for removal by intraoperative hemofiltration. Herein we describe the dosing and intraoperative management of bivalrudin anti-coagulation in a patient undergoing urgent cardiac transplantation in the context of recently diagnosed HIT.

Topics: Adult; Anticoagulants; Cardiomyopathy, Dilated; Combined Modality Therapy; Dose-Response Relationship, Drug; Heart Failure; Heart Transplantation; Hemofiltration; Heparin; Hirudins; Humans; Intraoperative Care; Male; Peptide Fragments; Recombinant Proteins; Thrombin; Thrombocytopenia