bivalirudin and Drug-Hypersensitivity

REG1 is a novel anticoagulation system consisting of pegnivacogin, an RNA aptamer inhibitor of coagulation factor IXa, and anivamersen, a complementary sequence reversal oligonucleotide. We tested the hypothesis that near complete inhibition of factor IXa with pegnivacogin during percutaneous coronary intervention, followed by partial reversal with anivamersen, would reduce ischaemic events compared with bivalirudin, without increasing bleeding.. We did a randomised, open-label, active-controlled, multicentre, superiority trial to compare REG1 with bivalirudin at 225 hospitals in North America and Europe. We planned to randomly allocate 13,200 patients undergoing percutaneous coronary intervention in a 1:1 ratio to either REG1 (pegnivacogin 1 mg/kg bolus [>99% factor IXa inhibition] followed by 80% reversal with anivamersen after percutaneous coronary intervention) or bivalirudin. Exclusion criteria included ST segment elevation myocardial infarction within 48 h. The primary efficacy endpoint was the composite of all-cause death, myocardial infarction, stroke, and unplanned target lesion revascularisation by day 3 after randomisation. The principal safety endpoint was major bleeding. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, identifier NCT01848106. The trial was terminated early after enrolment of 3232 patients due to severe allergic reactions.. 1616 patients were allocated REG1 and 1616 were assigned bivalirudin, of whom 1605 and 1601 patients, respectively, received the assigned treatment. Severe allergic reactions were reported in ten (1%) of 1605 patients receiving REG1 versus one (<1%) of 1601 patients treated with bivalirudin. The composite primary endpoint did not differ between groups, with 108 (7%) of 1616 patients assigned REG1 and 103 (6%) of 1616 allocated bivalirudin reporting a primary endpoint event (odds ratio [OR] 1·05, 95% CI 0·80-1·39; p=0·72). Major bleeding was similar between treatment groups (seven [<1%] of 1605 receiving REG1 vs two [<1%] of 1601 treated with bivalirudin; OR 3·49, 95% CI 0·73-16·82; p=0·10), but major or minor bleeding was increased with REG1 (104 [6%] vs 65 [4%]; 1·64, 1·19-2·25; p=0·002).. The reversible factor IXa inhibitor REG1, as currently formulated, is associated with severe allergic reactions. Although statistical power was limited because of early termination, there was no evidence that REG1 reduced ischaemic events or bleeding compared with bivalirudin.. Regado Biosciences Inc.

Topics: Aged; Anticoagulants; Aptamers, Nucleotide; Coagulants; Drug Hypersensitivity; Early Termination of Clinical Trials; Europe; Factor IXa; Female; Hemorrhage; Hirudins; Humans; Male; Middle Aged; North America; Oligonucleotides; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins

A 68-year-old male was admitted for implantation of an implantable cardioverter defibrillator (ICD). He had a prosthetic mechanical valve for which he was receiving anticoagulation with warfarin, but had developed an allergy to heparin. Therefore, we decided to use bivalirudin for anticoagulation, which permitted him to undergo the procedure without complications.

Topics: Aged; Anticoagulants; Cardiopulmonary Bypass; Defibrillators, Implantable; Drug Hypersensitivity; Fibrinolytic Agents; Heart Valve Prosthesis; Heparin; Hirudins; Humans; Male; Mitral Valve; Peptide Fragments; Prosthesis Implantation; Recombinant Proteins; Thrombosis; Warfarin

A patient with impaired left ventricular function was scheduled for coronary artery bypass grafting. The patient's history revealed a life-threatening allergy to fish proteins. Therefore, because of the threat of cross-reactivity to protamine, a standard anticoagulation protocol with heparin/protamine was disapproved. Instead, complete coronary artery revascularization was successfully performed off-pump using bivalirudin as the anticoagulant.

Topics: Anaphylaxis; Anticoagulants; Coronary Artery Bypass, Off-Pump; Coronary Artery Disease; Drug Hypersensitivity; Heparin Antagonists; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Protamines; Recombinant Proteins

Immune reactions to heparin and in particular heparin-induced thrombocytopenia are not rare and potentially fatal complications of heparin treatment. These conditions are frequently underdiagnosed in cardiac surgery. Moreover, few data are available in the literature about the use of alternative anticoagulants to heparin in this setting. We describe the successful use of bivalirudin in 2 patients with hypersensitivity to heparin who underwent cardiac surgery.

Topics: Aged; Aged, 80 and over; Anticoagulants; Cardiac Surgical Procedures; Drug Hypersensitivity; Female; Heparin; Hirudins; Humans; Peptide Fragments; Recombinant Proteins

The standard agent used for systemic anticoagulation during cardiopulmonary bypass is heparin. Alternative methods of anticoagulation are required for patients with heparin hypersensitivity. We present the case of a patient with heparin hypersensitivity who was anticoagulated with bivalirudin during cardiopulmonary bypass for coronary artery bypass grafting. This presented unusual challenges surrounding the monitoring of anticoagulation and the method of myocardial protection.

Topics: Adult; Anticoagulants; Cardiopulmonary Bypass; Combined Modality Therapy; Coronary Artery Bypass; Coronary Stenosis; Drug Hypersensitivity; Heparin; Hirudins; Humans; Male; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Ventricular Dysfunction, Left; Ventricular Fibrillation

Heparin-induced IgE-mediated hypersensitivity and anaphylactoid reactions, although rare, can pose a serious clinical problem for patients requiring cardiopulmonary bypass (CPB). Bivalirudin is a bivalent reversible direct thrombin inhibitor, with a half-life of 25 min, eliminated mostly by proteolytic cleavage. There are some reports on the use of bivalirudin for cardiac surgery, particularly for heparin-induced thrombocytopenia (HIT), but none on cases of heparin allergy. We report a case of heparin allergy successfully managed for CPB with bivalirudin anticoagulation.

Topics: Cardiopulmonary Bypass; Drug Hypersensitivity; Heparin; Hirudins; Humans; Immunoglobulin E; Male; Middle Aged; Peptide Fragments; Recombinant Proteins