bivalirudin and Thromboembolism

Bivalirudin may be an effective anticoagulation alternative to heparin as anticoagulant agent in percutaneous transcatheter aortic valve interventions (PAVI). We aimed to compare safety and efficacy of bivalirudin versus heparin as the procedural anticoagulant agent in patients undergoing PAVI.. We conducted an electronic database search of all published data. The primary efficacy endpoints were all-cause mortality, cardiovascular mortality, myocardial infarction, and stroke. Safety endpoints include major and life-threatening bleed according to VARC and BARC bleeding, blood transfusion, vascular complications, and acute kidney injury. Odds ratios (OR) and 95% confidence intervals (CI) computed using the Mantel-Haenszel method.. Three studies (n = 1690 patients) were included, one randomized trial and two observational studies. There was a significant difference favoring bivalirudin over heparin for myocardial infarction (OR 0.41, 95%CI 0.20-0.87). There was no significant difference in all-cause mortality at 30 days (OR 0.97, 95%CI 0.62-1.52), cardiovascular mortality (OR 1.03, 95%CI 0.52-2.05), stroke (OR 1.23, 95%CI 0.62-2.46), vascular complications (OR 0.96, 95%CI 0.70-1.32), acute kidney injury (OR 1.03, 95%CI 0.53-2.00), blood transfusion (OR 0.67, 95% CI 0.45-1.01), major and life-threatening bleed (OR 0.74, 95%CI 0.37-1.49), and BARC bleeding (OR 0.52, 95%CI 0.23-1.18).. In patient undergoing aortic valve interventions, no difference was seen between the use of bivalirudin and heparin as the procedural anticoagulant agent, except for a significant lower myocardial infarction events when bivalirudin was used. Further large randomized trials are needed to confirm current results.

Topics: Anticoagulants; Aortic Valve; Aortic Valve Stenosis; Balloon Valvuloplasty; Heparin; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; Thromboembolism; Transcatheter Aortic Valve Replacement

Anticoagulant drugs belong to the group of antithrombotic agents and are successfully used in the prophylaxis and treatment of thromboembolic disorders. The use of anticoagulants in the prevention of deep venous thrombosis has significantly lowered the risk of venous thrombosis and fatal pulmonary embolisms even in high-risk situations such as orthopedic surgery. Anticoagulants play a central role in the treatment of acute venous thrombosis and in the prevention of recurrent events. Long-term anticoagulation therapy with orally active anticoagulants significantly reduces the risk of thromboembolic complications in patients showing cardiac arrhythmias. Whereas a few years ago heparins and vitamin K antagonists were the dominant anticoagulants, today a wide range of anticoagulants with improved pharmacological profiles are available. It remains an open question whether these new anticoagulants will improve the efficacy, safety, and acceptance of anticoagulant treatment approaches.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Arginine; Arrhythmias, Cardiac; Blood Coagulation Tests; Factor Xa Inhibitors; Hemorrhage; Heparin; Heparinoids; Hirudins; Humans; Infusions, Intravenous; Orthopedic Procedures; Peptide Fragments; Pipecolic Acids; Postoperative Complications; Pulmonary Embolism; Recombinant Proteins; Risk Factors; Secondary Prevention; Sulfonamides; Thromboembolism; Treatment Outcome; Venous Thrombosis; Vitamin K

The coagulation cascade, and particularly thrombin, plays a very important role in arterial and venous thrombosis. Thereby, it is clear that thrombin inactivation is an optimal strategy for thrombotic disease prevention and treatment. The direct thrombin inhibitors are a new class of anticoagulant drugs directly binding thrombin and blocking its interaction with fibrinogen. The group of direct thrombin inhibitors includes recombinant hirudin (lepirudin and desirudin), bivalirudin, melagatran and its oral precursor, ximelagatran, argotraban and dabigatran. These drugs have several advantages compared to other anticoagulant drugs, and the particular pharmacokinetic properties of some of them could be very important for future management of thromboembolic prophylaxis. The efficacy and safety of these new drugs are evaluated in several clinical trials; however today only few clinical indications are available for the majority of them.

Topics: Anticoagulants; Antithrombins; Azetidines; Benzylamines; Clinical Trials as Topic; Drug Therapy, Combination; Fibrinolytic Agents; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; Thromboembolism; Treatment Outcome

Topics: Acute Disease; Angioplasty, Balloon, Coronary; Anticoagulants; Arginine; Atrial Fibrillation; Azetidines; Benzylamines; Clinical Trials as Topic; Coronary Disease; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Pipecolic Acids; Recombinant Proteins; Sulfonamides; Syndrome; Thrombin; Thromboembolism; Thrombosis; Venous Thrombosis

Inhibiting thrombin as a key enzyme of the coagulation cascade is therapeutically useful in thromboembolic diseases. In coronary thrombosis, direct thrombin inhibitors promise to be useful for an efficacious therapy. Hirudin and recombinant or synthetic mimetics like hirulog, argatroban and melagatran have proven their efficacy in clinical studies.. Therapy with direct thrombin inhibitors such as hirudin and analogous substances reduces coronary events. Moreover, the agents are useful for therapy of thromboembolic diseases, especially in the case of heparin induced thrombocytopenia type II.

Topics: Acute Disease; Angina, Unstable; Angioplasty, Balloon, Coronary; Animals; Anticoagulants; Antithrombins; Arginine; Azetidines; Benzylamines; Fibrinolytic Agents; Glycine; Hirudin Therapy; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Pipecolic Acids; Platelet Aggregation Inhibitors; Rabbits; Recombinant Proteins; Sulfonamides; Syndrome; Thrombin; Thromboembolism; Thrombosis; Time Factors

Anticoagulation is required during transcatheter aortic valve replacement (TAVR) procedures. Although an optimal regimen has not been determined, heparin is mainly used. Direct thrombin inhibition with bivalirudin may be an effective alternative to heparin as the procedural anticoagulant agent in this setting.. The goal of this study was to determine whether bivalirudin offers an alternative to heparin as the procedural anticoagulant agent in patients undergoing TAVR.. A total of 802 patients with aortic stenosis were randomized to undergo transfemoral TAVR with bivalirudin versus unfractionated heparin during the procedure. The 2 primary endpoints were major bleeding within 48 h or before hospital discharge (whichever occurred first) and 30-day net adverse clinical events, defined as the combination of major adverse cardiovascular events (all-cause mortality, myocardial infarction, or stroke) and major bleeding.. Anticoagulation with bivalirudin versus heparin did not meet superiority because it did not result in significantly lower rates of major bleeding at 48 h (6.9% vs. 9.0%; relative risk: 0.77; 95% confidence interval [CI]: 0.48 to 1.23; p = 0.27) or net adverse cardiovascular events at 30 days (14.4% vs. 16.1%; relative risk: 0.89; 95% CI: 0.64 to 1.24; risk difference: -1.72; 95% CI: -6.70 to 3.25; p = 0.50); regarding the latter, the prespecified noninferiority hypothesis was met (pnoninferiority < 0.01). Rates of major adverse cardiovascular events at 48 h were not significantly different (3.5% vs. 4.8%; relative risk: 0.73; 95% CI: 0.37 to 1.43; p = 0.35). At 48 h, the bivalirudin group had significantly fewer myocardial infarctions but more acute kidney injury events than the heparin group; at 30 days, these differences were no longer significant.. In this randomized trial of TAVR procedural pharmacotherapy, bivalirudin did not reduce rates of major bleeding at 48 h or net adverse cardiovascular events within 30 days compared with heparin. Although superiority was not shown, the noninferiority hypothesis was met with respect to the latter factor. Given the lower cost, heparin should remain the standard of care, and bivalirudin can be an alternative anticoagulant option in patients unable to receive heparin in TAVR. (International, Multi-center, Open-label, Randomized Controlled Trial in Patients Undergoing TAVR to Determine the Treatment Effect [Both Safety and Efficacy] of Using Bivalirudin Instead of UFH [BRAVO-2/3]; NCT01651780).

Topics: Aged, 80 and over; Anticoagulants; Antithrombins; Aortic Valve Stenosis; Dose-Response Relationship, Drug; Echocardiography; Europe; Female; Follow-Up Studies; Heparin; Hirudins; Humans; Incidence; Male; Peptide Fragments; Postoperative Hemorrhage; Recombinant Proteins; Retrospective Studies; Survival Rate; Thromboembolism; Transcatheter Aortic Valve Replacement; Treatment Outcome; United States

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.. 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.. 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.. 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.. 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.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Anthropology, Medical; Antithrombins; Cohort Studies; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Partial Thromboplastin Time; Peptide Fragments; Recombinant Proteins; Retrospective Studies; Risk Factors; Thrombocytopenia; Thromboembolism; Treatment Failure; Young Adult

Anticoagulation for cardiopulmonary bypass (CPB) is required to prevent acute disseminated intravascular coagulation and clot formation within the bypass circuit. Unfractionated heparin is the standard anticoagulant for CPB due to its many advantages and long history of successful use. However, heparin has the unique drawback of triggering Heparin-PF4 (PF4) antibodies potentially leading to heparin-induced thrombocytopenia (HIT). We have limited data regarding reformation of antibodies if a patient has had a prior (remote) antibody production or full HIT. Patients with antiphospholipid antibodies undergoing CPB with unfractionated heparin have a high complication rate, even in the absence of HIT. Antiphospholipid antibodies have a multifaceted, cumulatively inhibitory effect on the normal anticoagulation armamentarium in vivo. Even more concerning is the possibility that antiphospholipid syndrome and HIT may be synergistic. We report a patient with risk factors for both thromboembolic (remote history of HIT and antiphospholipid syndrome) and hemorrhagic complications who underwent an aortic valve replacement and coronary artery bypass grafting on CPB using bivalirudin. We discuss the complex decision making regarding anticoagulant for CPB, particularly with regard to American College of Chest Physicians guidelines.

Topics: Anticoagulants; Antiphospholipid Syndrome; Aortic Valve; Cardiopulmonary Bypass; Heart Valve Prosthesis Implantation; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Practice Guidelines as Topic; Recombinant Proteins; Risk Factors; Thrombocytopenia; Thromboembolism

Extracorporeal membrane oxygenation mandates balancing the risk of thromboembolic complications with bleeding. We aimed to evaluate pragmatic anticoagulation regimens during extracorporeal membrane oxygenation and compare thromboembolic and bleeding outcomes.. This retrospective, single-center study reviewed patients on venovenous or venoarterial extracorporeal membrane oxygenation for a minimum of 24 hours over a 5-year period. The primary outcome was composite thromboembolic events per day of extracorporeal membrane oxygenation. Secondary outcomes included composite bleeding complications, percent of measured activated partial thromboplastin times in goal range, and comparing events with therapeutic anticoagulation for the majority of the extracorporeal membrane oxygenation run (>50% of time on extracorporeal membrane oxygenation) versus non-therapeutic anticoagulation (therapeutic anticoagulation <50% of time).. For the primary analysis, 100 patients received heparin, 10 received bivalirudin, and 43 were transitioned between heparin and bivalirudin. No significant differences were identified comparing the heparin group to the bivalirudin (RR = 0.427, p = 0.156) or transitioned group (RR = 1.274, p = 0.325). There were no differences in the rate of bleeding events when comparing the heparin group to the bivalirudin (RR = 0.626, p = 0.250) or transitioned group (RR = 0.742, p = 0.116). An increased number of adjustments to the anticoagulants was associated with a statistically higher rate of bleeding events per day (p = 0.006).. There were no differences in thromboembolic or bleeding events when comparing different anticoagulant regimens. Adjustments to the anticoagulants are more likely to occur when bleeding is observed. Due to variability in anticoagulation, there is a need to standardize anticoagulation with extracorporeal membrane oxygenation.

Topics: Adult; Aged; Anticoagulants; Blood Coagulation; Extracorporeal Membrane Oxygenation; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Recombinant Proteins; Retrospective Studies; Thromboembolism

The referral of patients for open heart surgery, presenting with a history of heparin hypersensitivity instigated a multidisciplinary effort to find an alternative anticoagulant to heparin. The various options mentioned in the literature call for changes in the routine practice of open heart surgery on cardiopulmonary bypass. These changes involve mostly the perfusion setup and conduct on bypass and to a lesser extent the anesthetic and surgical practice. Nevertheless, the different professions involved in the cardiac surgical firm discussed the proposed changes in a multidisciplinary effort. A new protocol was drafted, endorsed, and executed. The authors highlight these changes and their successful use in the subsequent case study.

Topics: Aged; Algorithms; Anticoagulants; Cardiopulmonary Bypass; Combined Modality Therapy; Coronary Artery Disease; Drug Administration Schedule; Hirudins; Humans; Male; Peptide Fragments; Recombinant Proteins; Thromboembolism; Treatment Outcome

Thromboembolic events while receiving ventricular assist device (VAD) support remain a significant cause of morbidity and mortality despite standard anti-coagulation and anti-platelet therapies. The use of bivalirudin and epoprostenol infusions as an alternate anti-thrombotic (AT) regimen in pediatric VAD patients was reviewed.. This was a retrospective record review of 6 pediatric patients (aged ≤17 years) at 2 institutions treated with bivalirudin and epoprostenol infusions while being supported with the Berlin Heart EXCOR (Berlin Heart GmbH, Berlin, Germany) VAD.. Six patients (age, 0.8-14 years; weight, 6.7-29.7 kg) were treated. Diagnoses included cardiomyopathy in 2 and congenital heart disease in 4. VAD support was left VAD in 2 and bi-VAD in 4, with duration of support of 21 to 155 days. Three patients required extracorporeal membrane oxygenation before VAD support. Bivalirudin/epoprostenol was used after recurrent thromboses on conventional medication in 3 patients, heparin-induced thrombocytopenia in 2, and in 1 patient considered high risk with a prosthetic mitral valve. The bivalirudin dose was titrated to partial thromboplastin time (PTT) of 1.5- to 2-times baseline (0.1-0.8 mg/kg/hour); the epoprostenol dose was 2 to 10 ng/kg/min. Additional anti-platelet agents included acetylsalicylic acid, dipyridamole, and clopidogrel in 5 patients each. No bleeding complications occurred. One patient sustained a cerebrovascular infarct on therapy, with subsequent complete recovery. No other complications occurred. Five patients underwent successful transplantation, and 1 patient died of multisystem organ failure.. This report provides data on estimated safety and efficacy of bivalirudin and epoprostenol as an AT strategy in pediatric patients on extended VAD support. The short drug half-life and predictable AT response facilitated conversion to standard AT regimens at the time of transplantation (heparin-induced thrombocytopenia-negative patients). These agents should be considered for management of pediatric VAD patients when standard regimens fail.

Topics: Adolescent; Cardiomyopathies; Child; Child, Preschool; Disease Management; Dose-Response Relationship, Drug; Epoprostenol; Fibrinolytic Agents; Heart Defects, Congenital; Heart-Assist Devices; Hirudins; Humans; Infant; Peptide Fragments; Recombinant Proteins; Retrospective Studies; Thromboembolism; Treatment Outcome

Bivalirudin is an ultrashort acting direct thrombin inhibitor, which has been used in place of heparin in selected settings. We describe our preliminary experience with the use of bivalirudin in patients who required anticoagulation for a deep vein thrombosis, prosthetic heart valve, or hypercoagulable state but were felt to be at high risk for the use of heparin.. Eight patients in our neurocritical care unit required anticoagulation but were felt to be poor candidates for heparin either due to heparin-induced thrombocytopenia or due to high risk for intracranial hemorrhage. A standard protocol was utilized for bivalirudin with a loading dose of 0.75 mg/kg followed by a continuous infusion of 0.15 mg/kg hr. Serial aPTT levels were checked on a routine basis to monitor therapeutic effect. The bivalirudin infusion was continued for a period of 2 days to 2 weeks prior to starting coumadin therapy.. These patients were in the early postoperative period (within 48 h) following craniotomy, had suffered a recent large hemispheric infarct with hemorrhagic conversion, or had presented with an acute intracerebral hemorrhage. In this small series of patients, no intracranial hemorrhagic complications were encountered. No patients demonstrated progressive systemic thrombotic issues while on bivalirudin.. Based on these findings, bivalirudin may represent a reasonable alternative in patients for whom heparin anticoagulation is contraindicated. A larger multicenter trial of bivalirudin in this setting may be appropriate.

Topics: Adult; Aged; Aged, 80 and over; Antithrombins; Female; Heart Valve Prosthesis; Hirudins; Humans; Intracranial Hemorrhages; Male; Middle Aged; Peptide Fragments; Recombinant Proteins; Retrospective Studies; Thromboembolism; Thrombophilia; Treatment Outcome; Venous Thrombosis

Topics: Animals; Anticoagulants; Antithrombins; Clinical Trials as Topic; Heart Valve Prosthesis; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; Thrombin; Thrombocytopenia; Thromboembolism

Topics: Anticoagulants; Carotid Stenosis; Catheterization; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Hirudins; Humans; Male; Peptide Fragments; Radiography; Randomized Controlled Trials as Topic; Recombinant Proteins; Sensitivity and Specificity; Stents; Thromboembolism

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