bivalirudin and Postoperative-Complications

Despite several randomized controlled trials and meta-analyses, the ideal anticoagulant for patients undergoing primary percutaneous coronary intervention (PCI) remains controversial. We performed an updated meta-analysis including recently reported randomized clinical trials that compare bivalirudin and heparin with or without provisional administration of a glycoprotein IIb/IIIa inhibitor (GPI) for primary PCI.. Scientific databases and Web sites were searched for randomized clinical trials. Data from 6 trials involving 14,095 patients were included. The pooled risk ratios (RRs) were calculated using random-effects models. Moderator analyses examined the impact of routine use of GPI, radial access, and P2Y12 inhibitors on safety outcomes. At 30 days, patients receiving bivalirudin had rates of major adverse cardiac events similar to those receiving heparin with or without provisional GPI (RR 1.02, 95% CI 0.87-1.19, P = .800), myocardial infarction (RR 1.41, 95% CI 0.94-2.11, P = .089), target vessel revascularization (RR 1.37, 95% CI 0.91-2.04, P = .122), and net adverse clinical events (RR 0.81, 95% CI 0.64-1.01, P = .069). However, bivalirudin use decreased the risk of all-cause mortality (RR 0.81, 95% CI 0.67-0.99, P = .041) and cardiac mortality (RR 0.68, 95% CI 0.51-0.91, P = .009) at 30 days, There were higher rates of acute stent thrombosis (RR 3.31, 95% CI 1.79-6.10, P < .001) in patients receiving bivalirudin. Bivalirudin use also decreased the risk of major bleeding at 30 days by 37% (RR 0.63, 95% CI 0.44-0.90, P = .012), but bleeding risk varied depending on routine GPI use with heparin (RR 0.44, 95% CI 0.23-0.81, P = .009) vs bailout (RR 0.73, 95% CI 0.42-1.25, P = .252), predominantly radial access (RR 0.54, 95% CI 0.25-1.15, P = .114) vs non-radial access (RR 0.60, 95% CI 0.36-0.99, P = .049), and second-generation P2Y12 inhibitor use with bivalirudin (RR 0.70, 95% CI 0.40-1.24, P = .226) vs clopidogrel use (RR 0.39, 95% CI 0.18-0.85, P = .018).. In primary PCI, relative to heparin, bivalirudin reduces the risk for all-cause mortality, cardiac mortality, and major bleeding but yields similar rates of major adverse cardiac event and net adverse clinical event at 30 days. However, the benefit of a reduction in bleeding with bivalirudin appears to be modulated by the concurrent administration of second-generation P2Y12 inhibitors with bivalirudin, using radial access, and avoiding routine GPI use with heparin.

Topics: Anticoagulants; Antithrombins; Global Health; Heparin; Hirudins; Humans; Incidence; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Postoperative Complications; Recombinant Proteins; Survival Rate

The efficacy and safety of bivalirudin versus heparin in patients undergoing percutaneous coronary intervention (PCI)(1) remains controversial in to date. Our meta-analysis was undertaken to evaluate the efficacy and safety of bivalirudin compared with heparin in patients undergoing PCI.. We searched PubMed, Cochrane Library, EMBASE, Clinical Trials.gov databases for randomized controlled trials (RCTs).(2) The primary efficacy endpoint was mortality. Secondary efficacy endpoints were incidence of major adverse cardiovascular events (MACE),(3) myocardial infarction (MI),(4) target vessel revascularization (TVR)(5) and stent thrombosis up to 30days and 1year. The safety endpoint was major bleeding up to 30days. Subgroup analyses were also conducted according to the clinical status of patients and the different use rate of GPI in two groups.. 17 RCTs met the including criteria and 40,655 patients were included. No significant difference was observed in mortality (risk ratio [RR](6) 0.90; 95% confidence interval [CI](7) 0.77 to 1.05; p=0.19; I(2)=20%) and the risk of MACE (RR 1.02; 95% CI 0.96 to 1.09; p=0.45; I(2)=37%). Bivalirudin increased the risk of MI (RR 1.10; 95% CI 1.02 to 1.19; p=0.01; I(2)=13%), TVR (RR 1.20; 95% CI 1.04 to 1.38; p=0.01; I(2)=6%) and stent thrombosis (RR 1.32; 95% CI 1.08 to 1.60; p=0.006; I(2)=0%) but decreased the risk of major bleeding (RR 0.54; 95% CI 0.48 to 0.61; p<0.00001; I(2)=0).. Bivalirudin is associated with higher risk of MI, stent thrombosis and TVR but lower risk of major bleeding compared with heparin. The reduction of major bleeding is associated with the glycoprotein platelet IIb/IIIa inhibitor (GPI)(8) use rate.

Topics: Heparin; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Postoperative Complications; Randomized Controlled Trials as Topic; Recombinant Proteins; Survival Analysis; Treatment Outcome

Bleeding complications are among the most common complications of percutaneous coronary intervention (PCI) procedures. A multitude of studies carried out over the last decade have confirmed that bleeding complications after PCI have a negative impact on patients' outcome (dissatisfaction, morbidity, and mortality) and hospital indices (length of stay and costs). Apart from better recognition and classification of bleeding, recent research has helped to device several risk stratification tools that have markedly improved prediction of peri-PCI bleeding. Moreover, parallel with the recognition of the deleterious effects of peri-PCI bleeding, several strategies (pre-PCI risk stratification for bleeding, the use of bivalirudin as an antithrombotic/anticoagulant strategy, the radial artery route for vascular access and vascular closure devices) that aim to reduce peri-PCI bleeding were developed and used. Their application has markedly reduced the incidence of bleeding and improved the clinical outcome. In this review, we focus primarily on the bleeding complications occurring during PCI procedures. Specifically, we summarize recent research on the need for a consensus in bleeding definition, incidence of bleeding events, and their impact on outcome, factors associated with increased risk and risk stratification for bleeding, putative mechanisms through which bleeding impact on outcome, and bleeding-avoidance strategies to be used in the setting of PCI procedures.

Topics: Antithrombins; Hemorrhage; Hirudins; Humans; Incidence; Outcome Assessment, Health Care; Peptide Fragments; Percutaneous Coronary Intervention; Postoperative Complications; Prognosis; Recombinant Proteins; Risk Adjustment; Risk Factors; Vascular Closure Devices

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

Percutaneous coronary intervention (PCI) is currently the standard of care for patients presenting with acute coronary syndrome (ACS), as well those patients with "stable" angina who have failed medical therapy in whom PCI is an acceptable alternative to surgical revascularization. The aim of adjunctive antiplatelet and antithrombotic therapy during PCI is to alleviate the risks associated with platelet activation and aggregation, iatrogenic plaque rupture, and thrombus formation during. The aim of this review is to summarize the evidence that has emerged from the randomized studies comparing a strategy combining heparin and a glycoprotein IIb/IIIa inhibitor (GPI) with that of bivalirudin in patients undergoing elective and urgent PCI.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Antithrombins; Drug Therapy, Combination; Heparin; Hirudins; Humans; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Complications; Recombinant Proteins

With femoral access, bivalirudin decreases risks of major bleeding after percutaneous coronary intervention (PCI) and provides better net clinical benefit compared to unfractionated heparin (UFH) plus planned glycoprotein IIb/IIIa inhibitors. Whether this benefit exists compared to UFH monotherapy is less clear. We performed a systematic review and meta-analysis to compare outcomes in patients undergoing transfemoral PCI with UFH or bivalirudin. Randomized trials (n = 3) and observational studies (n = 13) comparing bivalirudin to UFH monotherapy were reviewed. Primary outcomes were 30-day rates of major adverse cardiovascular events (MACEs) including death, myocardial infarction (MI), urgent revascularization, as well as all-cause mortality, MI, major bleeding, and blood transfusion. We collected data from 16 studies involving 32,492 patients undergoing PCI. Most observational studies were performed in the United States, whereas all randomized trials were done in Europe. Compared to UFH monotherapy, bivalirudin was associated with similar risk of MACEs (odds ratios [OR] 0.92, 95% confidence interval [CI] 0.75 to 1.12), a substantial 45% relative decrease in major bleeding (OR 0.55, 95% CI 0.43 to 0.72), and a trend in the decrease of transfusion (OR 0.87, 95% CI 0.70 to 1.08). A decrease in mortality was seen in observational studies (OR 0.62, 95% CI 0.45 to 0.85) but remained inconclusive in randomized trials (OR 0.63, 95% CI 0.20 to 2.01). MI rate was similar with the 2 anticoagulants. In conclusion, in patients undergoing transfemoral PCI, the benefit of bivalirudin over UFH monotherapy is driven by a significant decrease in major bleeding with similar rates of MACE. As PCI practice moves toward other bleeding-avoidance strategies such as the radial approach, future studies should focus on the interaction between anticoagulant strategy and access-site choice.

Topics: Angioplasty, Balloon, Coronary; Antithrombins; Cardiovascular Diseases; Heparin; Hirudins; Humans; Myocardial Ischemia; Peptide Fragments; Postoperative Complications; Postoperative Hemorrhage; Recombinant Proteins; Treatment Outcome

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Clinical Trials as Topic; Coronary Thrombosis; Endothelium, Vascular; Enoxaparin; Fibrinolytic Agents; Fondaparinux; Hirudins; Humans; Myocardial Ischemia; Peptide Fragments; Platelet Activation; Polysaccharides; Postoperative Complications; Recombinant Proteins; Thrombin

Heparin induced thrombocytopenia (HIT) in addition to bleeding complications are the most serious and dangerous side effects of heparin treatment. HIT remains the most common antibody-mediated, drug-induced thrombocytopenic disorder and a leading cause of morbidity and mortality. Two types of HIT are described: Type I is a transitory, slight and asymptomatic reduction of platelet count occurring during 1-2 days of therapy. HIT type II, which has an immunologic origin, is characterized by a thrombocytopenia that generally onset after the fifth day of therapy. Despite thrombocytopenia, haemorrhagic complications are very rare and HIT type II is characterized by thromboembolic complications consisting in venous and arterial thrombosis. The aim of this paper is to review new aspects of epidemiology, pathophysiology, clinical features, diagnosis and therapy of HIT type II. There is increasing evidence that platelet factor 4 (PF4) displaced from endothelial cells, heparan sulphate or directly from the platelets, binds to heparin molecule to form an immunogenic complex. The anti-heparin/PF4 IgG immune-complexes activates platelets through binding with the Fcgamma RIIa (CD32) receptor inducing endothelial lesions with thrombocytopenia and thrombosis. Cytokines are generated during this process and inflammation could play an additional role in the pathogenesis of thromboembolic manifestations. The onset of HIT type II is independent from dosage, schedule, and route of administration of heparin. A platelet count must be carried out prior to heparin therapy. Starting from the fourth day, platelet count must be carried out daily or every two days for at least 20 days of any heparin therapy regardless of the route of the drug administration. Patients undergoing orthopaedic or cardiac surgery are at higher risk for HIT type II. The diagnosis of HIT type II should be formulated on basis of clinical criteria and confirmed by in vitro demonstration of heparin-dependent antibodies detected by functional and antigen methods. However, the introduction of sensitive ELISA tests to measure anti-heparin/PF4 antibodies has showed the immuno-conversion in an higher number of patients treated with heparin such as the incidence of anti-heparin/PF4 exceeds the incidence of the disease. If HIT type II is likely, heparin must be immediately discontinued, even in absence of certain diagnosis of HIT type II, and an alternative anticoagulant therapy must be started followed by oral dicuma

Topics: Animals; Anticoagulants; Arginine; Chondroitin Sulfates; Dermatan Sulfate; Heparin; Heparitin Sulfate; Hirudins; Humans; Peptide Fragments; Pipecolic Acids; Postoperative Complications; Recombinant Proteins; Sulfonamides; Thrombocytopenia

The recognition and management of heparin-induced thrombocytopenia (HIT) and heparin-induced thrombocytopenia with thrombosis syndrome (HITTS) has been evolving over the past several years. Although HIT is a relatively uncommon adverse event in patients receiving heparin therapy, it bears a significant risk of thrombotic events. If patients are left untreated, 50% can develop thrombosis. Several direct thrombin inhibitors have been studied as alternative anticoagulants in patients with HIT. Lepirudin and argatroban are both approved by the United States Food and Drug Administration (FDA) for the management of HIT. Lepirudin requires dosage adjustments in patients with renal insufficiency and has potential for antibody formation. Argatroban requires dosage adjustments in patients with hepatic insufficiency. Argatroban increases the international normalized ratio when coadministered with warfarin, leading to dosage difficulties when transitioning to warfarin therapy. Bivalirudin is the most recent direct thrombin inhibitor to be introduced to the market, but it is not currently FDA approved for HIT. Controversy still exists over which direct thrombin inhibitor to use, especially in acutely ill patients and in those requiring invasive or surgical procedures. Bivalirudin has a relatively short half-life and a predictable response, which makes it attractive as an anticoagulant in patients requiring invasive or surgical procedures, those who are acutely ill, or patients with both renal and hepatic insufficiency. It offers promise as an additional direct thrombin inhibitor for use in patients with HIT, but additional studies need to be performed to further define its use.

Topics: Anticoagulants; Clinical Trials as Topic; Heparin; Hirudins; Humans; Peptide Fragments; Postoperative Complications; Recombinant Proteins; Thrombin; Thrombocytopenia

Bivalirudin (Hirulog, Angiomax) is a specific, reversible and direct thrombin inhibitor with a predictable anticoagulant effect. It is cleared by both proteolytic cleavage and renal mechanisms, predominantly glomerular filtration. Bivalirudin inhibits both circulating thrombin and fibrin bound thrombin directly by binding to thrombin catalytic site and anion-binding exosite I in a concentration-dependent manner. Bivalirudin prolongs activated partial thromboplastin time, prothrombin time, thrombin time and activated clotting time (ACT). ACT levels with bivalirudin do not correlate with its clinical efficacy. Bivalirudin with a provisional GpIIb/IIIa inhibitor is indicated in elective contemporary percutaneous coronary intervention (PCI). In respect to combined ischemic and hemorrhagic endpoints of death, myocardial infarction, unplanned urgent revascularization and major bleeding during PCI (including subgroups of patients with renal impairment and diabetes) bivalirudin is not inferior to unfractioned heparin and planned GpIIb/IIIa inhibitors. In addition, bivalirudin has been consistently shown to have significantly less in-hospital major bleeding than heparin alone or heparin in combination with a GpIIb/IIIa inhibitor. Bivalirudin appears to be also safe and effective during PCI in patients with heparin-induced thrombocytopenia. Finally, data from PCI studies support the safety and efficacy of bivalirudin, although its direct randomized comparison with unfractionated heparin is lacking.

Topics: Angioplasty, Balloon, Coronary; Animals; Anticoagulants; Cardiopulmonary Bypass; Coronary Disease; Cost-Benefit Analysis; Hirudins; Humans; Peptide Fragments; Postoperative Complications; Recombinant Proteins; Thrombin

Unfractionated heparin given during cardiopulmonary bypass is remarkably immunogenic, as 25% to 50% of postcardiac surgery patients develop heparin-dependent antibodies during the next 5 to 10 days. Sometimes, these antibodies strongly activate platelets and coagulation, thereby causing the prothrombotic disorder, heparin-induced thrombocytopenia. The risk of heparin-induced thrombocytopenia is 1% to 3% if unfractionated heparin is continued beyond the first postoperative week. When cardiac surgery is urgently needed for a patient with acute or subacute heparin-induced thrombocytopenia, options include an alternative anticoagulant (bivalirudin, lepirudin, or danaparoid) or combining unfractionated heparin with a platelet antagonist (epoprostenol or tirofiban). As heparin-induced thrombocytopenia antibodies are transient, unfractionated heparin alone is appropriate in a patient with previous heparin-induced thrombocytopenia whose antibodies have disappeared.

Topics: Anticoagulants; Cardiac Surgical Procedures; Diagnosis, Differential; Female; Heparin; Hirudin Therapy; Hirudins; Humans; Male; Peptide Fragments; Postoperative Complications; Recombinant Proteins; Thrombocytopenia; Thrombosis

The treatment of patients with acute coronary syndromes has changed dramatically over the last several years. Most patients now undergo some form of percutaneous coronary intervention (PCI), which includes either stent placement or percutaneous transluminal coronary angioplasty (PTCA). Along with new medical interventions for acute coronary syndromes comes the need for new antithrombotic therapies. Combination therapy with antiplatelet agents (aspirin, adenosine diphosphate inhibitors), glycoprotein (GP) IIb-IIIa receptor inhibitors, and anticoagulants (unfractionated heparin or low-molecular-weight heparins) is administered, depending on the type of intervention and severity of the coronary lesion. Bivalirudin is a direct thrombin inhibitor that recently was approved as an alternative to heparin in patients undergoing PTCA. Compared with unfractionated heparin, bivalirudin reduces the rate of death, myocardial infarction, or revascularization, with a concurrent reduction in bleeding. This agent offers promise as a replacement for unfractionated heparin in PCI and is being studied in comparison with unfractionated heparin plus GP IIb-IIIa receptor inhibitors in patients undergoing intracoronary stent placement.

Topics: Angioplasty, Balloon, Coronary; Hemorrhage; Heparin, Low-Molecular-Weight; Hirudins; Humans; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Complications; Randomized Controlled Trials as Topic; Recombinant Proteins; Thrombin; Thrombocytopenia; Thrombosis; Treatment Outcome

Revascularization procedures and particularly percutaneous transluminal coronary angioplasty are being performed more and more often in patients with unstable coronary artery disease, despite the fact that these procedures are known to carry a higher risk in such patients than in those with stable disease. This article reviews studies that have investigated the potential of modern antithrombotic therapy -- low-molecular-weight heparin, anti-Xa agents, direct antithrombin inhibitors and glycoprotein IIb/IIIa inhibitors -- to reduce the post-procedural event rate in such patients. The results are promising.

Topics: Abciximab; Angina, Unstable; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Anticoagulants; Aspirin; Clinical Trials as Topic; Combined Modality Therapy; Diabetes Complications; Drug Therapy, Combination; Eptifibatide; Factor Xa Inhibitors; Heparin, Low-Molecular-Weight; Hirudin Therapy; Hirudins; Humans; Immunoglobulin Fab Fragments; Myocardial Revascularization; Oligosaccharides; Peptide Fragments; Peptides; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Complications; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Factors; Thrombocytopenia; Thrombosis; Time Factors; Tirofiban; Treatment Outcome; Tyrosine

Most of the clinical evaluation of the direct thrombin inhibitors has been in coronary artery disease. The recent clinical reports suggest that there is a narrower window of safety with recombinant hirudin than initially thought particularly when it is used in conjunction with thrombolytic agents and aspirin in acute myocardial infarction. The efficacy data, however, indicate that the direct thrombin inhibitors have great potential particularly in the initial management of patients with acute unstable angina and non-Q-wave infarction. There is much to learn regarding the mechanism of action, optimal dose, and optimal concomitant therapy in the use of direct thrombin inhibitors in the management of acute coronary ischaemia; and since hirudin and other direct thrombin inhibitors have so much potential in the management of acute coronary ischaemia, it is critical that dose-finding studies be performed to determine safe regimens of these agents to allow their evaluation in large-scale trials with important clinical outcomes. The direct thrombin inhibitors have also shown to have promise in the prevention of deep vein thrombosis in high-risk surgical patients. There is limited clinical data on the other novel anticoagulants which are currently being developed.

Topics: Angina, Unstable; Angioplasty, Balloon, Coronary; Antithrombins; Aspirin; Clinical Trials as Topic; Clinical Trials, Phase II as Topic; Dose-Response Relationship, Drug; Double-Blind Method; Drug Design; Drug Therapy, Combination; Enzyme Activation; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Hirudin Therapy; Hirudins; Humans; Lipoproteins; Myocardial Infarction; Myocardial Ischemia; Peptide Fragments; Platelet Aggregation Inhibitors; Postoperative Complications; Protein C; Randomized Controlled Trials as Topic; Recombinant Proteins; Thrombolytic Therapy; Thrombophlebitis; Treatment Outcome

Topics: Animals; Anticoagulants; Antithrombin III; Antithrombin III Deficiency; Aprotinin; Blood Coagulation Tests; Cardiopulmonary Bypass; Heparin; Hirudin Therapy; Hirudins; Humans; Intraoperative Complications; Peptide Fragments; Postoperative Complications; Recombinant Proteins; Thrombin; Thrombosis; Warfarin

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.

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Female; Follow-Up Studies; Hemorrhage; Heparin; Hirudins; Humans; Incidence; Male; Peptide Fragments; Postoperative Complications; Recombinant Proteins; Time Factors; Transcatheter Aortic Valve Replacement

Recent randomized controlled trials comparing femoral and radial access in primary percutaneous coronary intervention (PPCI) have shown conflicting results regarding the incidence of major adverse cardiovascular events (MACE) and major bleeding.. Using data from the HEAT-PPCI trial, we compared the primary efficacy (all-cause mortality, stroke, new myocardial infarction or unplanned repeat revascularization) and safety (major bleeding BARC 3-5) outcomes at 28 days, by final access site used (radial or femoral) and by default operator type. We then assessed outcomes in femoral cases performed by both operator types.. Radial access (RA) was associated with fewer MACE (91/1472 = 6.2% vs. 36/332 = 10.8% P = .003) and major bleeding events (38/1472 = 2.6% vs 22/332 = 6.6% P = .001) when compared to femoral access (FA). When analyzing outcomes by default operator type, there was a similar incidence of MACE (111/1575 = 7% vs 16/229 = 7% P = .97) and major bleeding events (49/1575 = 3.1% vs 11/229 = 4.8% P = .18). In cases where FA was performed by default radial operators, there was a higher rate of MACE (22/122 = 18% vs 14/210 = 6.7% P = .003) and major bleeding events (11/122 = 9% vs 11/210 = 5.2% P < .001), potentially explained by a higher risk profile in these cases.. Default femoral operators achieved comparable outcomes when compared to default radial operators. The less favorable outcomes observed in FA cases may result from its selective use by radial operators in high risk cases.

Topics: Aged; Anticoagulants; Antithrombins; Cause of Death; Femoral Artery; Heparin; Hirudins; Humans; Incidence; Middle Aged; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Postoperative Complications; Postoperative Hemorrhage; Pressure; Radial Artery; Recombinant Proteins; Recurrence; Reoperation; ST Elevation Myocardial Infarction; Stroke; Surgeons; Treatment Outcome; Vascular Closure Devices

Contrasting evidence exists on the comparative efficacy and safety of bivalirudin and unfractionated heparin (UFH) in relation to the planned use of glycoprotein IIb/IIIa inhibitors (GPIs).. This study assessed the efficacy and safety of bivalirudin compared with UFH with or without GPIs in patients with acute coronary syndrome (ACS) who underwent invasive management.. In the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX) program, 7,213 patients were randomly assigned to receive either bivalirudin or UFH with or without GPIs at discretion of the operator. The 30-day coprimary outcomes were major adverse cardiovascular events (MACEs) (a composite of death, myocardial infarction, or stroke), and net adverse clinical events (NACEs) (a composite of MACEs or major bleeding).. Among 3,603 patients assigned to receive UFH, 781 (21.7%) underwent planned treatment with GPI before coronary intervention. Bailout use of GPIs was similar between the bivalirudin and UFH groups (4.5% and 5.4%) (p = 0.11). At 30 days, the 2 coprimary endpoints of MACEs and NACEs, as well as individual endpoints of mortality, myocardial infarction, stent thrombosis or stroke did not differ among the 3 groups after adjustment. Compared with the UFH and UFH+GPI groups, bivalirudin reduced bleeding, mainly the most severe bleeds, including fatal and nonaccess site-related events, as well as transfusion rates and the need for surgical access site repair. These findings were not influenced by the administered intraprocedural dose of UFH and were confirmed at multiple sensitivity analyses, including the randomly allocated access site.. In patients with ACS, the rates of MACEs and NACEs were not significantly lower with bivalirudin than with UFH, irrespective of planned GPI use. However, bivalirudin significantly reduced bleeding complications, mainly those not related to access site, irrespective of planned use of GPIs. (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX [MATRIX]; NCT01433627).

Topics: Acute Coronary Syndrome; Aged; Coronary Artery Bypass; Electrocardiography; Female; Hematologic Agents; Hemorrhage; Heparin; Hirudins; Humans; Intraoperative Care; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Complications; Recombinant Proteins; Treatment Outcome

Post-procedural anticoagulation (AC) for routine prophylaxis may be administered after primary percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI), but the risks and benefits of this practice are uncertain. We therefore sought to assess the utility of routine post-procedural AC after primary PCI.. Patients undergoing primary PCI in the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial were grouped according to whether they received post-PCI AC for routine prophylaxis. Outcomes were assessed using propensity-adjusted multivariable analysis. Among 2932 patients in whom primary PCI for STEMI was performed, 869 (29.6%) received post-PCI AC for routine prophylaxis (median duration four days) and 2063 (70.4%) received no post-PCI AC. Time from PCI to ambulation was similar in both groups (median 0.9 vs 1.0 days, p=0.40), although hospitalization was prolonged in patients receiving AC for routine prophylaxis (median 6.0 vs 4.0 days, p<0.0001). After propensity-adjustment, patients who received and did not receive AC for routine prophylaxis after PCI experienced similar rates of 30-day adverse ischemic and major bleeding events. Deep venous thrombosis or pulmonary emboli developed rarely (0.3%) within 30 days, and were not significantly reduced by use of post-PCI AC for routine prophylaxis.. In this large-scale prospective study, use of post-procedural AC for routine prophylaxis was relatively common, and was not associated with improved clinical outcomes, although the duration of hospitalization was prolonged. These data suggest that post-PCI AC for routine prophylaxis may not provide benefit after successful primary PCI in patients in whom early ambulation is likely.

Topics: Aged; Antithrombins; Aspirin; Clopidogrel; Dose-Response Relationship, Drug; Drug Therapy, Combination; Drug-Eluting Stents; Electrocardiography; Female; Fibrinolytic Agents; Follow-Up Studies; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Care; Postoperative Complications; Prospective Studies; Recombinant Proteins; Secondary Prevention; ST Elevation Myocardial Infarction; Survival Rate; Thrombolytic Therapy; Ticlopidine; Treatment Outcome

Bivalirudin has been associated with reduced bleeding and mortality during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (STEMI). However, increased rates of acute stent thrombosis (AST) have been noted when bivalirudin is discontinued at the end of the procedure, which is perhaps related to this medication's short half-life.. To evaluate the clinical effect of procedure duration on AST when either bivalirudin or heparin plus glycoprotein IIb/IIIa receptor inhibitor (GPI) is used.. An ad hoc analysis of the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) clinical trial was performed between March 1, 2015, and April 30, 2016, on patients who underwent primary percutaneous coronary intervention with stents and were randomized 1:1 to bivalirudin or heparin plus GPI. Defined as the difference between the patient's arrival at the catheterization laboratory and the patient's final angiogram. Participants included 3602 patients with STEMI, aged 18 years or older, who were undergoing primary percutaneous coronary intervention and presenting less than 12 hours from symptom onset.. Clinical events committee-adjudicated definite AST (occurring ≤24 hours after percutaneous coronary intervention).. Among patients included in this analysis, procedure time was identified in 1286 receiving bivalirudin and 1412 receiving heparin plus GPI. Shorter procedures were defined as the lowest quartile of duration (<45 minutes). Patients undergoing shorter procedures were younger and less likely to be hypertensive and smokers. Shorter procedures were less complicated with fewer stents implanted, less multivessel stenting, less thrombus, and less no-reflow. An increased risk of definite AST was associated with shorter than with longer procedures with bivalirudin (7 [2.1%] vs 7 [0.7%]; relative risk, 2.87; 95% CI, 1.01-8.17; P = .04) but not with heparin plus GPI (0 vs 3 [0.3%]; P = .30).. Despite less procedural complexity, shorter primary percutaneous coronary intervention time was associated with an increased risk of AST in patients treated with bivalirudin but not patients treated with heparin plus GPI, possibly because of the rapid offset of bivalirudin's antithrombotic effect during a window of limited oral antiplatelet action.. clinicaltrials.gov Identifier: NCT00433966.

Topics: Acute Disease; Aged; Anticoagulants; Antithrombins; Drug Therapy, Combination; Female; Heparin; Hirudins; Humans; Male; Middle Aged; Operative Time; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Complications; Recombinant Proteins; Risk Factors; ST Elevation Myocardial Infarction; Stents; Thrombosis

Early stent thrombosis (ST) within 30 days after primary percutaneous coronary intervention in ST-segment-elevation myocardial infarction is a serious event. We sought to determine the predictors of and risk of mortality after early ST according to procedural antithrombotic therapy.. In a patient-level pooled analysis from the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) and European Ambulance Acute Coronary Syndrome Angiography (EUROMAX) trials, we examined 30-day outcomes in 4935 patients undergoing primary percutaneous coronary intervention with stent implantation at 188 international sites, randomized to either bivalirudin or heparin±a glycoprotein IIb/IIIa inhibitor (GPI). Early ST occurred in 100 patients (2.0%), 20 of whom (20.0%) died. Bivalirudin was associated with higher rates of early ST compared with heparin±GPI (2.5% versus 1.6%, P=0.04), because of more acute (≤24 h) ST (1.5% versus 0.2%, P<0.0001), with the risk limited to the first 4 hours after percutaneous coronary intervention. The rates of subacute (1-30 days) ST were similar with bivalirudin and heparin±GPI (1.0% versus 1.4%, P=0.24). Among patients with early ST, mortality within 30 days occurred in 4 of 60 (6.7%) bivalirudin-treated patients compared with 16 of 40 (40.0%) heparin±GPI-treated patients (adjusted hazard ratio, 0.12; 95% CI, 0.04-0.39; P=0.0004 and adjusted hazard ratio, 0.122; 95% CI, 0.04-0.39; P=0. 0004). Thus, 30-day mortality attributable to early ST occurred in 4 of 2479 (0.2%) bivalirudin-treated patients versus 16 of 2456 (0.7%) heparin±GPI-treated patients (P=0.007).. In the present large-scale pooled analysis from 2 multicenter randomized trials, early ST was more frequent in patients treated with bivalirudin compared with heparin±GPI because of increased ST within 4 hours after primary percutaneous coronary intervention. However, the mortality attributable to early ST was significantly lower after bivalirudin than after heparin±GPI.. URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00433966 (HORIZONS-AMI) and NCT01087723 (EUROMAX).

Topics: Aged; Blood Vessel Prosthesis Implantation; Electrocardiography; Female; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Patient Outcome Assessment; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Complications; Recombinant Proteins; Stents; Survival Analysis; Thrombosis

In the HORIZONS-AMI trial, bivalirudin compared to unfractionated heparin (UFH) plus a glycoprotein IIb/IIIa inhibitor (GPI) improved net clinical outcomes in patients undergoing primary percutaneous coronary intervention (PCI) at the cost of an increased rate of acute stent thrombosis. We sought to examine whether these effects are dependent on time to treatment.. The interaction between anticoagulation regimen and symptom onset to first balloon inflation time (SBT) on the 30-day and three-year rates of major adverse cardiac events (MACE) was examined in 3,199 randomised patients according to SBT ≤3 hours versus >3 hours. Among patients with an SBT ≤3 hours, bivalirudin resulted in higher 30-day rates of MACE compared to UFH plus a GPI. Non-significant differences were observed in patients with an SBT >3 hours. Similar results were found for MACE at three years and stent thrombosis and reinfarction at 30 days and three years. By multivariable analysis, bivalirudin was an independent predictor of MACE at 30 days and three years in patients with an SBT ≤3 hours, but not in patients with SBT >3 hours.. Bivalirudin compared to UFH plus a GPI is associated with an increased rate of stent thrombosis and MACE in patients with short SBTs, but not in those with longer SBTs.

Topics: Aged; Anticoagulants; Antithrombins; Cause of Death; Drug Therapy, Combination; Female; Graft Occlusion, Vascular; Heparin; Hirudins; Humans; Male; Middle Aged; Mortality; Myocardial Infarction; Myocardial Revascularization; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Complications; Recombinant Proteins; Recurrence; ST Elevation Myocardial Infarction; Stroke; Thrombosis; Time-to-Treatment; Treatment Outcome

Target vessel revascularization (TVR) may compromise the benefits of primary percutaneous coronary intervention in ST-segment elevation myocardial infarction (STEMI) We set out to identify the predictors and examine the impact of TVR after STEMI in patients receiving a coronary stent.. In HORIZONS-AMI, 3,602 patients with STEMI were randomized to bivalirudin versus heparin and a glycoprotein IIb/IIIa inhibitor. Stents were implanted in 3,202 patients (2,982 were randomized to bare-metal stents versus paclitaxel-eluting stents, and 220 received nonrandomized stents).. Target vessel revascularization occurred in 219 patients (6.9%) at 1 year and in 437 patients (14.4%) at 3 years. Target vessel revascularization was ischemia-driven in 418 cases (95.7%). Target vessel revascularization was due to restenosis in 219 patients (50.1%), definite stent thrombosis in 124 (28.4%), and disease progression in 94 (21.5%). Independent predictors of TVR were more extensive coronary artery disease, smaller vessel size, longer lesion length and the number of stents implanted, post-percutaneous coronary intervention diameter stenosis, symptom onset to balloon time, treatment with bare-metal stents rather than paclitaxel-eluting stents, and scheduled angiographic follow-up. Target vessel revascularization was an independent predictor of subsequent myocardial infarction (hazard ratio [HR] 5.25, P < .0001), ST (HR 5.98, P < .0001), and major bleeding (HR 5.25, P < .0001) but not mortality (HR 0.88, P = .61).. In HORIZONS-AMI, TVR within 3 years after stent implantation was performed in ~1 of every 7 patients and was associated with more extensive coronary disease, more complex procedures, and bare metal stents. Target vessel revascularization was often due to stent thrombosis and disease progression as well as restenosis and was strongly associated with adverse outcomes but not mortality.

Topics: Angioplasty, Balloon, Coronary; Antineoplastic Agents, Phytogenic; Antithrombins; Coronary Angiography; Coronary Restenosis; Disease Progression; Drug-Eluting Stents; Electrocardiography; Female; Hemorrhage; Heparin; Hirudins; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Outcome Assessment, Health Care; Paclitaxel; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Complications; Prognosis; Recombinant Proteins; Reoperation

Reinfarction after primary percutaneous coronary intervention in patients with ST-segment-elevation myocardial infarction has negative consequences. Little is known about reinfarction after drug-eluting stents and bivalirudin anticoagulation. We, therefore, sought to determine the incidence, predictors, and implications of reinfarction after primary percutaneous coronary intervention in the contemporary era.. Outcomes were assessed in 3202 patients undergoing stent implantation for ST-segment-elevation myocardial infarction in the Harmonizing Outcomes with RevascularIZatiON and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial. Independent predictors of reinfarction and mortality were identified by Cox proportional hazards modeling. The cumulative incidence of reinfarction was 1.8% at 30 days, 4.0% at 1 year, and 6.9% at 3 years. Definite stent thrombosis was responsible for 76.3% of reinfarctions occurring within 30 days and 52.0% of all reinfarctions within 3 years. Independent predictors of reinfarction were current smoking, Killip class ≥2, baseline thrombocytosis, multivessel disease, symptom onset-to-balloon time, and total stent length. Randomization to bivalirudin versus heparin plus a glycoprotein IIb/IIIa inhibitor and use of drug-eluting versus bare metal stents were not significant predictors of reinfarction. Reinfarction was a powerful independent predictor of subsequent cardiac mortality (hazard ratio [95% confidence interval]=7.65 [4.47-13.09]; P<0.0001) and all-cause mortality (hazard ratio [95% confidence interval]=2.88 [1.74-4.78]; P<0.0001).. Despite advances in pharmacotherapy and stents, reinfarction after primary percutaneous coronary intervention is not infrequent, in the contemporary era is most often attributable to stent thrombosis, and is strongly associated with subsequent cardiac and all-cause mortality. Further enhancements in drugs and devices to prevent reinfarction are needed to improve outcomes in high-risk patients with ST-segment-elevation myocardial infarction.. http://www.clinicaltrials.gov. Unique identifier: NCT00433966.

Topics: Acute Disease; Aged; Antithrombins; Drug-Eluting Stents; Electrocardiography; Female; Follow-Up Studies; Heparin; Hirudins; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Complications; Prospective Studies; Recombinant Proteins; Recurrence; Risk Factors; Survival Analysis; Thrombosis; Treatment Outcome

Bivalirudin, a direct thrombin inhibitor, is as effective as unfractionated heparin (UFH), with decreased bleeding in patients with acute coronary syndromes who undergo percutaneous coronary intervention (PCI). The aim of this study was to evaluate the effectiveness of bivalirudin versus UFH in selected PCI patients at high bleeding risk. Four hundred one consecutive patients who underwent PCI fulfilling ≥ 1 enrollment criterion (age >75 years, chronic renal failure, and diabetes mellitus) were randomized to bivalirudin (bolus 0.75 mg/kg followed by infusion during the procedure; n = 198) or UFH (75 IU/kg; n = 203). In the overall population, 39% were aged >75 years, 22% had renal failure, 63% had diabetes, and 29% had acute coronary syndromes. The primary efficacy end point was the 30-day incidence of major adverse cardiac events (cardiac death, myocardial infarction, stent thrombosis, or target vessel revascularization). The primary safety end point was the occurrence of any bleeding or entry-site complications after PCI. All patients were preloaded with clopidogrel 600 mg. Glycoprotein IIb/IIIa inhibitors were used at the operators' discretion. Thirty-day major adverse cardiac event rates were 11.1% in the bivalirudin group and 8.9% in the UFH group (p = 0.56); the primary efficacy end point was reached mainly because of periprocedural myocardial infarction; 1 patient in the bivalirudin group had stent thrombosis. Occurrence of the primary safety end point was 1.5% in the bivalirudin group and 9.9% in the UFH group (p = 0.0001); this benefit was essentially driven by the prevention of entry-site hematomas >10 cm (0.5% vs 6.9%, p = 0.002). In conclusion, Anti-Thrombotic Strategy for Reduction of Myocardial Damage During Angioplasty-Bivalirudin vs Heparin (ARMYDA-7 BIVALVE) indicates that bivalirudin, compared with UFH, causes significantly lower bleeding and has a similar incidence of major adverse cardiac events in patients with older age, diabetes mellitus, or chronic renal failure who undergo PCI.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Antithrombins; Coronary Artery Disease; Diabetes Complications; Drug Therapy, Combination; Female; Heart Diseases; Heparin; Hirudins; Humans; Incidence; Male; Myocardial Infarction; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Complications; Postoperative Hemorrhage; Recombinant Proteins; Renal Insufficiency; Treatment Outcome

Unfractionated heparin and its antidote, protamine sulfate, allow for rapid and reversible anticoagulation during cardiac surgery with cardiopulmonary bypass, yet limitations exist, including a variable dose-response, dependence on a cofactor for anticoagulant effect, and antigenic potential. This trial was performed to evaluate the safety and efficacy of bivalirudin as an alternative to heparin with protamine reversal in on-pump cardiac surgery.. We conducted a randomized, open-label, multicenter trial comparing heparin with protamine reversal to bivalirudin in patients undergoing cardiac surgery with cardiopulmonary bypass. The primary objective was to demonstrate comparable rates of in-hospital procedural success defined as freedom from death, Q-wave myocardial infarction, stroke, or repeat revascularization. Twenty-one institutions enrolled 101 patients randomized to bivalirudin and 49 patients to heparin treatment.. The primary end point of procedural success was not significantly different between the bivalirudin arm and the heparin/protamine arms at 7 days, 30 days, or 12 weeks' follow-up. Adequate anticoagulation was achieved in all patients. Secondary end points including mortality, 24-hour blood loss, overall incidence of transfusions, and duration of surgery were similar between the two arms.. Bivalirudin is a safe and effective anticoagulant for patients undergoing a wide range of cardiac surgical procedures with cardiopulmonary bypass. Procedural success rates with bivalirudin were similar to rates in patients receiving heparin anticoagulation, with no difference in mortality. Avoidance of blood stasis and attention to the intraoperative medical management of patients is critical for successful use of bivalirudin during cardiopulmonary bypass.

Topics: Aged; Anticoagulants; Cardiopulmonary Bypass; Female; Heparin; Heparin Antagonists; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Postoperative Complications; Protamines; Recombinant Proteins; Thrombocytopenia; Thrombosis

Unfractionated heparin has many shortcomings, including indirect and partial inhibition of thrombin, antibody formation, and platelet activation. Bivalirudin, a short-acting direct thrombin inhibitor, avoids these limitations and has superior outcomes during percutaneous revascularization. This trial was performed to evaluate the safety and efficacy of bivalirudin in off-pump coronary artery bypass grafting.. An open-label, multicenter randomized trial compared heparin with protamine reversal to bivalirudin in patients undergoing off-pump coronary artery bypass. The primary objective was safety as demonstrated by similar rates of procedural success defined as freedom from a composite of death, myocardial infarction, stroke, and repeat revascularization. Twenty-one institutions randomized 105 patients to receive bivalirudin and 52 patients to receive heparin.. The mean age was 65 years for both groups. The bivalirudin group had more grafts: 3.0 +/- 1 versus 2.5 +/- 1. Procedural success rates at 30 days were identical in bivalirudin- and heparin-treated patients (93%). Operative times, total blood loss, reoperations for bleeding, and major adverse events were not significantly different. Strokes were more frequent in the heparin group: 5.5% versus 0; P = .05. Mortality was 2% in each group. Repeat revascularization was required in 3% of bivalirudin- and 2% of the heparin-treated patients.. For patients undergoing off-pump coronary artery bypass grafting, bivalirudin was an effective anticoagulant, without excessive bleeding and with a safety profile similar to that of heparin. Further trials are warranted to assess whether anticoagulation with bivalirudin improves clinical outcomes.

Topics: Aged; Anticoagulants; Coronary Artery Bypass, Off-Pump; Female; Heparin; Heparin Antagonists; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Postoperative Complications; Protamines; Recombinant Proteins

The goal of this study was to evaluate glycoprotein IIb/IIIa inhibition with eptifibatide when administered with indirect thrombin inhibition as compared with monotherapy with direct thrombin inhibition with bivalirudin among patients with non-ST-segment elevation acute coronary syndromes (ACS).. The optimal combination of antiplatelet and antithrombin regimens that maximizes efficacy and minimizes bleeding among patients with non-ST-segment elevation ACS undergoing percutaneous coronary intervention (PCI) is unclear.. A total of 857 patients with non-ST-segment elevation ACS were assigned randomly to eptifibatide + reduced dose unfractionated heparin (n = 298), eptifibatide + reduced-dose enoxaparin (n = 275), or bivalirudin monotherapy (n = 284).. Among angiographically evaluable patients (n = 754), the primary end point of post-PCI coronary flow reserve was significantly greater with bivalirudin (1.43 vs. 1.33 for pooled eptifibatide arms, p = 0.036). Thrombolysis In Myocardial Infarction (TIMI) myocardial perfusion grade more often was normal with eptifibatide treatment compared with bivalirudin (57.9% vs. 50.9%, p = 0.048). The duration of ischemia on continuous Holter monitoring after PCI was significantly longer among patients treated with bivalirudin (169 vs. 36 min, p = 0.013). There was no excess of TIMI major bleeding among patients treated with eptifibatide compared with bivalirudin (0.7%, n = 4 vs. 0%, p = NS), but TIMI minor bleeding was increased (2.5% vs. 0.4%, p = 0.027) as was transfusion (4.4% to 0.4%, p < 0.001).. Among moderate- to high-risk patients with ACS undergoing PCI, coronary flow reserve was greater with bivalirudin than eptifibatide. Eptifibatide improved myocardial perfusion and reduced the duration of post-PCI ischemia but was associated with higher minor bleeding and transfusion rates. Ischemic events and biomarkers for myonecrosis, inflammation, and thrombin generation did not differ between agents.

Topics: Acute Disease; Angina, Unstable; Angioplasty, Balloon, Coronary; Antithrombins; Drug Therapy, Combination; Enoxaparin; Eptifibatide; Female; Fibrinolytic Agents; Heparin; Hirudins; Humans; Inflammation; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Peptide Fragments; Peptides; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Complications; Postoperative Hemorrhage; Recombinant Proteins; Syndrome

In the EVOLUTION OFF trial, we evaluated the safety and efficacy of bivalirudin during off-pump coronary artery bypass grafting as compared with heparin-protamine. In this subanalysis of EVOLUTION OFF data of bivalirudin-treated patients, we assessed the pharmacokinetics (PK) and effectiveness of bivalirudin anticoagulation to achieve target activated clotting time (ACT)+ values. Data from 101 patients were assessed. A bolus of 0.75 mg/kg of bivalirudin was followed by a continuous infusion of 1.75 mg x kg(-1) x h(-1) during the grafting procedure. An ACT+ value of >300 s was the target. In four patients, PK data for bivalirudin were obtained. Only in exceptional cases were repeat fractional boluses or an increase of the infusion rate required. Assessment of the PK data showed a mean concentration of bivalirudin after the initial bolus of 11.0 +/- 0.53 microg/mL and a mean concentration during infusion of 11.2 +/- 2.32 microg/mL. Pearson's correlation between bivalirudin concentrations and ACT+ values was 0.92. Bivalirudin PK data consistently exceeded concentrations of 6.5 microg/mL, which have been evaluated as effective during percutaneous coronary intervention. The correlation between bivalirudin levels and ACT+ values was good, and the target ACT+ values were almost always achieved. These results suggest that bivalirudin, given according to the current protocol, provides reliable and effective anticoagulation during off-pump coronary artery bypass graft surgery.

Topics: Aged; Anticoagulants; Coronary Artery Bypass; Coronary Artery Bypass, Off-Pump; Female; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Revascularization; Peptide Fragments; Postoperative Complications; Protamines; Recombinant Proteins; Time Factors

Bivalirudin (Angiomax) is increasingly used as a substitute for heparin in a variety of percutaneous coronary interventions, and data on its usage in saphenous vein graft interventions are limited. This retrospective, observational study evaluated the efficacy and safety of bivalirudin compared with heparin as an antithrombotic regimen in patients who underwent saphenous vein graft intervention with distal protection devices. We found that bivalirudin use is clinically safe and feasible, with fewer vascular and ischemic complications compared with heparin.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Coronary Artery Disease; Female; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Postoperative Complications; Recombinant Proteins; Retrospective Studies; Saphenous Vein; Stents; Thrombosis; Treatment Outcome

To assess the efficacy of the direct thrombin inhibitor bivalirudin relative to heparin during contemporary coronary intervention, 1,056 patients who underwent elective or urgent revascularization were randomized in a large-scale pilot study to receive heparin (70 U/kg initial bolus) or bivalirudin (0.75 mg/kg bolus, 1.75 mg/kg/hour infusion during the procedure). All patients received aspirin; pretreatment with clopidogrel was encouraged, and glycoprotein (GP) IIb/IIIa blockade was at the physician's discretion. Stents were placed in 85% of patients; 72% received a GP IIb/IIIa inhibitor, and 56% were pretreated with clopidogrel. Activated clotting times were higher among patients randomized to bivalirudin than among those given heparin before device activation (median 359 vs 293 seconds, p <0.001). The composite efficacy end point of death, myocardial infarction, or repeat revascularization before hospital discharge or within 48 hours occurred in 5.6% and 6.9% of patients in the bivalirudin and heparin groups, respectively (p = 0.40). Major bleeding occurred in 2.1% versus 2.7% of patients randomized to bivalirudin or heparin, respectively (p = 0.52). This trial represents the largest prospective dataset of bivalirudin administered concomitantly with planned GP IIb/IIIa blockade and provides evidence of the safety and efficacy of this combined antithrombotic approach.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Dose-Response Relationship, Drug; Female; Heparin; Hirudins; Humans; Intraoperative Care; Male; Middle Aged; Peptide Fragments; Pilot Projects; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Complications; Postoperative Hemorrhage; Recombinant Proteins; Treatment Outcome; United States; Whole Blood Coagulation Time

Heparin is often administered during and after coronary angioplasty to prevent closure of the dilated vessel. However, ischemic or hemorrhagic complications occur in 5 to 10 percent of treated patients. We studied whether these complications could be prevented when the direct thrombin inhibitor bivalirudin (Hirulog) was used in place of heparin.. We performed a double-blind, randomized trial in 4098 patients undergoing angioplasty for unstable or postinfarction angina. Patients were assigned to receive either heparin or bivalirudin immediately before angioplasty. The primary end point were death in the hospital, myocardial infarction, abrupt vessel closure, or rapid clinical deterioration of cardiac origin.. In the total study group, bivalirudin did not significantly reduce the incidence of the primary end point (11.4 percent, vs. 12.2 percent for heparin) but did result in a lower incidence of bleeding (3.8 percent vs. 9.8 percent, P < 0.001). In the prospectively stratified subgroup of 704 patients with postinfarction angina, bivalirudin therapy resulted in a lower incidence of the primary end point (9.1 percent vs. 14.2 percent, P = 0.04) and a lower incidence of bleeding (3.0 percent vs. 11.1 percent, P < 0.001), but in a similar cumulative rate of death, myocardial infarction, and repeated revascularization in the six months after angioplasty (20.5 percent vs. 25.1 percent, P = 0.17).. Bivalirudin was at least as effective as high-dose heparin in preventing ischemic complications in patients who underwent angioplasty for unstable angina, and it carried a lower risk of bleeding. Bivalirudin, as compared with heparin, reduced the risk of immediate ischemic complications in patients with postinfarction angina, but this difference was no longer apparent after six months.

Topics: Aged; Angina Pectoris; Angina, Unstable; Angioplasty, Balloon, Coronary; Double-Blind Method; Female; Hemorrhage; Heparin; Hirudin Therapy; Hirudins; Humans; Ischemia; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Postoperative Complications; Recombinant Proteins; Serine Proteinase Inhibitors

The study objective was to determine whether Hirulog, a direct thrombin inhibitor, has potential efficacy and safety in the prevention of deep vein thrombosis (DVT) in orthopedic patients. A phase 2 open-label, dose-escalating design was used to study 222 unselected patients undergoing major hip or knee surgery in tertiary-care, university-affiliated hospitals.. Subcutaneous Hirulog was initiated postoperatively. Patients were evaluated for bleeding and symptomatic pulmonary embolism, and mandatory bilateral venography was performed before discharge. Dose escalations were made on the basis of observed rates of bleeding and venous thrombosis. There were five dosage regimens used: 0.3 mg/kg every 12 hours, 0.6 mg/kg every 12 hours, 1.0 mg/kg every 12 hours for 3 days followed by 0.6 mg/kg every 12 hours for up to 11 days, 1.0 mg/kg every 12 hours, and 1.0 mg/kg every 8 hours. One hundred seventy-seven patients who had technically adequate bilateral venography or objectively documented pulmonary embolism were included in the primary analysis of efficacy. The highest dosage regimen (1.0 mg/kg every 8 hours) provided the lowest rates of total DVT (17%) and proximal DVT (2%), both of which were significantly lower (P = .010 and P = .023, respectively) than the pooled rates of total (43%) and proximal (20%) DVT seen with the first four regimens. Bleeding rates were low (< 5%) with all regimens.. This study demonstrates that 1.0 mg/kg Hirulog every 8 hours started postoperatively is potentially efficacious and safe for the prevention of DVT after major hip or knee surgery.

Topics: Aged; Female; Hip Prosthesis; Hirudin Therapy; Hirudins; Humans; Knee Prosthesis; Male; Middle Aged; Peptide Fragments; Postoperative Complications; Recombinant Proteins; Thrombin; Thrombophlebitis

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.. 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.. 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.

Topics: Antithrombins; Hepatic Artery; Hirudins; Humans; Infant; Liver Transplantation; Male; Ornithine Carbamoyltransferase Deficiency Disease; Peptide Fragments; Postoperative Complications; Recombinant Proteins; Thrombosis

Clinicians use validated scores to risk-stratify patients undergoing transcatheter aortic valve replacement (TAVR). However, evaluation by the Heart Team often deems patients to be at higher risk than their formal scores suggest. We sought to assess clinical outcomes of TAVR patients defined as high-risk by the Heart Team's assessment versus the patient's logistic EuroSCORE (LES).. The BRAVO-3 trial randomized patients at high risk (LES ≥ 18, or deemed inoperable by the Heart Team) to TAVR with periprocedural anticoagulation with unfractionated heparin versus bivalirudin. Endpoints included net adverse cardiac events (NACE: the composite of all-cause mortality, MI, stroke, or bleeding), major adverse cardiovascular events (MACE: death, MI, or stroke), the individual components of MACE, major vascular complications, BARC ≥ 3b bleeding and VARC life-threatening bleeding at 30 days. We compared patients deemed high-risk based on LES ≥ 18 versus high-risk by the Heart Team despite lower LES.. A total of 467/800 (58.4%) patients were deemed high-risk by the Heart Team despite LES < 18. After multivariable analysis, there were no differences in the odds of endpoints between groups (NACE, OR. Patients undergoing TAVR and labeled high-risk by LES ≥ 18 or Heart Team assessment despite LES < 18 have comparable short-term outcomes. Assignment of high-risk status to over 50% of patients is attributable to Heart Team's clinical assessment.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Aortic Valve; Aortic Valve Stenosis; Clinical Decision-Making; Decision Support Techniques; Female; Hemodynamics; Heparin; Hirudins; Humans; Male; Patient Care Team; Patient Selection; Peptide Fragments; Postoperative Complications; Predictive Value of Tests; Randomized Controlled Trials as Topic; Recombinant Proteins; Retrospective Studies; Risk Assessment; Risk Factors; Severity of Illness Index; Transcatheter Aortic Valve Replacement; Treatment Outcome

A pharmacoinvasive strategy for ST-segment elevation myocardial infarction (STEMI) management combines the use of fibrinolysis with the routine transfer to coronary angiography, with percutaneous coronary intervention (PCI) if needed. This method reduces the risk of major adverse cardiovascular event (MACE) compared with fibrinolysis alone; however, it is associated with higher bleeding risk. We sought to assess the bivalirudin compared with unfractionated heparin (UFH) used during PCI as part of a pharmacoinvasive strategy.. We identified consecutive patients referred to the University of Ottawa Heart Institute between April 2009 and May 2011 as part of a pharmacoinvasive strategy for STEMI. The primary efficacy outcome was MACE, defined as a composite of death, reinfarction, or stroke during index hospitalization. The primary safety outcome was TIMI bleeding.. We identified 200 patients meeting inclusion criteria: 123 patients (61.5%) in the bivalirudin group and 77 patients (37.5%) in the UFH group. Median fibrinolysis to balloon time was 324 minutes in the bivalirudin group and 226 minutes in the UFH group (P<.001). Initial TIMI grade 3 flow was higher in the bivalirudin group vs the UFH group, but there was no difference in the rates post PCI. MACE rates were 4.9% vs 7.8% (P=.40) and TIMI bleeding rates were 7.3% vs 11.7% (P=.29) in patients treated with bivalirudin vs UFH, respectively.. The periprocedural use of bivalirudin vs UFH was associated with similar rates of MACE and bleeding. Given the expense of bivalirudin and lack of demonstrable clinical superiority, UFH remains the first-line periprocedural anticoagulant in a pharmacoinvasive strategy.

Topics: Coronary Angiography; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Outcome and Process Assessment, Health Care; Peptide Fragments; Percutaneous Coronary Intervention; Perioperative Care; Postoperative Complications; Recombinant Proteins; Risk Adjustment; ST Elevation Myocardial Infarction

The goal of this study was to review the feasibility of local bivalirudin injection for adjunct treatment of venous congestion of head and neck reconstructive flaps.. A retrospective chart review of patients who underwent bivalirudin treatment for venous congestion of head and neck reconstructive flaps in a single institution from September 1, 2012 to September 1, 2015 was undertaken. Individuals were treated with variable number of intradermal injections directly into the flap followed by a small skin incision to allow extended passive bleeding. The main outcome measure was improvement of flap congestion.. Ten patients with free flap reconstruction (4 anterolateral thigh flaps, 2 pectoralis major flaps, 2 fibula osseocutaneous flaps, 1 supraclavicular flap, and 1 radial forearm free flap) of various head and neck defects underwent treatment with bivalirudin. Bivalirudin injections were utilized as adjunct therapy in 6 patients. Two individuals underwent alternate therapy for venous congestion immediately following injection and therefore the efficacy could not be assessed. Of the 8 remaining flaps, 4 developed partial necrosis, and 1 developed complete necrosis requiring additional reconstruction. Two individuals required blood transfusions during bivalirudin treatment.. Bivalirudin is a safe and feasible adjunct therapy for treatment of flap congestion. It may serve as a useful alternative to traditional leech therapy, as bivalirudin negates the need for antibiotic prophylaxis, eliminates the psychological aversion associated with leech therapy, and avoids the potential for leech migration. Further work to determine the efficacy of bivalirudin to standard leech therapy is warranted.

Topics: Adult; Aged; Aged, 80 and over; Antithrombins; Combined Modality Therapy; Female; Free Tissue Flaps; Head and Neck Neoplasms; Hirudins; Humans; Hyperemia; Leeching; Male; Microsurgery; Middle Aged; Peptide Fragments; Plastic Surgery Procedures; Postoperative Complications; Recombinant Proteins; Retrospective Studies

The optimal antithrombotic regimen for urgent percutaneous coronary interventions (PCI) following thrombolytic therapy for ST segment myocardial infarction (STEMI) is currently unknown.. We performed a retrospective analysis of all patients referred to our institution from January 2005 to July 2014 who underwent urgent PCI within 24 hr after receiving thrombolytic therapy. The patients were divided into three cohorts based on the anticoagulation strategy during PCI-bivalirudin, heparin alone or heparin plus Glycoprotein IIb/IIIa inhibitor (GPI). The primary end point of major adverse cardiovascular events (MACE) was defined as a composite of inpatient death, myocardial infarction (MI) and stroke. Net adverse clinical events (NACE) were defined as a combination of MACE plus major bleeding complications. Univariable, multivariable and propensity-weighted modeling were used to compare MACE and NACE between the three treatment groups.. A total of 695 patients met the inclusion criteria during the study period. In the univariable analysis, there was no significant difference treatment in MACE between the three groups (Bivalirudin: 1.2% vs. Heparin + GPI: 4.4%; Heparin alone: 2.7%, P = 0.11). In the reduced logistic regression model, compared to bivalirudin, the odds of NACE was significantly higher with heparin alone (OR: 3.58, 95% CI: 1.21, 10.54, P = 0.02) or with heparin plus GPI (OR: 9.0, 95% CI: 2.83, 28.64, P <0.001).. In STEMI patients undergoing PCI within 24 hr after thrombolytic therapy, bivalirudin was associated with a strong trend toward reduced bleeding complications as compared to heparin alone or heparin plus GPI. The optimal antithrombotic regiment for urgent PCI following thrombolytic therapy is currently unknown. Our study demonstrated that use of bivalirudin during PCI following thrombolytic therapy is associated with a trend toward reduced bleeding complications compared to heparin alone or heparin plus GPI. Large randomized trials of adjunctive anticoagulation during PCI in this complex post-thrombolytic population are warranted. © 2017 Wiley Periodicals, Inc.

Topics: Anticoagulants; Drug Therapy, Combination; Female; Follow-Up Studies; Heparin; Hirudins; Humans; Incidence; Male; Massachusetts; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Complications; Recombinant Proteins; Retrospective Studies; ST Elevation Myocardial Infarction; Survival Rate; Thrombolytic Therapy; Treatment Outcome

The beneficial effects of bivalirudin during primary PCIs are controversially discussed, data on unselected patients are rare. It was the aim of the study to compare bivalirudin versus heparin and provisional glycoprotein IIb/IIIa inhibitors (GPIs) in a "real-world" study.. From 05/2013 until 11/2014, the STEMI-patients in the Bremen STEMI registry were treated with periinterventional bivalirudin; before and after this period the standard anticoagulative treatment was heparin and provisional GPIs.. In 714 patients bivalirudin was used for PCI, this cohort was compared to 683 patients with heparin and provisional GPIs. In patients with bivalirudin a significantly lower rate of hospital bleedings was observed compared to patients with heparin (4.6% vs 8.1%, P < 0.01, multivariate HR 0.57, 95%CI 0.35-0.93), in an exclusive analysis of severe bleedings a trend toward less bleedings was found in patients with bivalirudin (2.0% vs 3.5%, P = 0.07, multivariate HR 0.66, 95%CI 0.30-1.42). The rate of stent thromboses reinfarctions and mortality was not different between the bivalirudin and the heparin group. During 1-year follow-up bivalirudin was associated with a lower rate of bleedings and no significant differences in stent thromboses, reinfarctions, and mortality. Bivalirudin was not associated with an excess of bleedings or stent thromboses in subgroups that are regularly underrepresented in randomized trials (older patients, women, cardiogenic shock).. In this "real-world" cohort of patients with STEMI bivalirudin compared to heparin and GPIs was associated with less bleedings and no significant differences in stent thromboses, reinfarctions, and mortality during hospital and long-term course.

Topics: Aged; Antithrombins; Female; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Complications; Recombinant Proteins; Registries; Retrospective Studies; ST Elevation Myocardial Infarction; Treatment Outcome

Heparin-induced thrombocytopenia (HIT) results in platelet consumption and a virulent thrombotic state, which generally responds to cessation of heparin and initiation of anticoagulation. Rarely, delayed HIT can occur and/or persist after heparin is discontinued.. A 47-year-old male developed delayed HIT with severe thrombocytopenia and thrombosis after cardiac surgery. Thrombocytopenia developed and persisted after heparin cessation and did not improve despite sequential use of argatroban followed by bivalirudin. Treatment with intravenous immunoglobulin (IVIg) was well tolerated and resulted in rapid resolution of thrombocytopenia.. There are few case reports on the management of delayed HIT with severe and prolonged thrombocytopenia. The risk for thrombosis and bleeding in the setting of an undefined time course increases uncertainty in management.. This case, along with others accumulating in the literature, suggest that IVIg may be effective in treating delayed HIT with persistent thrombocytopenia.

Topics: Arginine; Cardiac Surgical Procedures; Heparin; Hirudins; Humans; Immunoglobulins, Intravenous; Male; Middle Aged; Peptide Fragments; Pipecolic Acids; Postoperative Complications; Recombinant Proteins; Sulfonamides; Thrombocytopenia; Thrombosis

Peripheral vascular interventions are increasingly preferred for the treatment of patients with symptomatic peripheral arterial disease because they are associated with similar clinical outcomes and lower morbidity than open surgical procedures. The objective of this study was to assess the comparative effectiveness of procedural anticoagulation with bivalirudin compared with unfractionated heparin in patients undergoing peripheral vascular interventions.. This was a retrospective, observational study using the Premier Hospital administrative database. We examined 23,934 consecutive patients undergoing lower extremity peripheral vascular interventions between January 2008 and December 2012 who were treated with either bivalirudin or unfractionated heparin. In-hospital end points included death, myocardial infarction, transfusion, stroke, amputation, and the composite end points of major adverse cardiovascular events, and net adverse clinical events. Propensity score matching was performed to control for baseline imbalances and yielded 3649 matched pairs. After propensity score matching, patients treated with bivalirudin had lower in-hospital event rates with significantly lower mortality (odds ratio, 0.40; P=0.017), need for blood product transfusion (odds ratio, 0.74; P=0.009), major adverse cardiovascular events (odds ratio, 0.64; P=0.003), and net adverse clinical events (odds ratio, 0.72; P<0.001). These associations were observed consistently across clinically relevant subgroups.. In patients undergoing peripheral vascular interventions, procedural anticoagulation with bivalirudin may result in more favorable in-hospital outcomes compared with unfractionated heparin, the current standard of care. These observations will require prospective confirmation in a randomized, controlled trial.

Topics: Aged; Anticoagulants; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Heparin; Hirudins; Hospital Mortality; Humans; Incidence; Male; Myocardial Infarction; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Postoperative Complications; Propensity Score; Recombinant Proteins; Retrospective Studies; Survival Rate; Time Factors; Treatment Outcome; United States

Topics: Antithrombins; Blood Coagulation; Coronary Restenosis; Hemorrhage; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation; Postoperative Complications; Recombinant Proteins; Risk Assessment

Anticoagulation with unfractionated heparin (UFH) in critically ill cardiac surgery patients has several limitations, including the risk of heparin-induced thrombocytopenia. The use of a direct thrombin inhibitor, such as bivalirudin, might either treat this complication or completely eliminate it. The aim of the present study was to analyze the use of bivalirudin in this setting, as either a secondary drug switching from heparin or as the primary anticoagulant, and to evaluate clinical outcomes.. Propensity-matching retrospective analysis.. A cardiac surgery intensive care unit.. One hundred propensity-matched patients who received heparin or bivalirudin.. Bivalirudin was administered as a first-line or second-line drug after heparin discontinuation in case of thrombocytopenia and suspicion of heparin-induced thrombocytopenia. Twenty-six patients (52%) received bivalirudin as a primary anticoagulant, while 24 patients (48%) received bivalirudin after switching from heparin.. Bivalirudin treatment was associated with a reduction of major bleeding (p=0.05) compared with the control group. Interestingly, in an intention-to-treat analysis, patients receiving primary bivalirudin showed significant reductions in minor bleeding (p=0.04), and mortality (p=0.01) compared with the secondary bivalirudin group and, similarly, compared with the rest of the study population (UFH and secondary bivalirudin patients, p=0.01 and p=0.05, respectively). Predictors of hospital mortality by multivariate analysis included urgent admission (odds ratio [OR]=2.7; 95 confidence interval [CI], 1.03-7.2; p=0.04), ;septic shock (OR=8.0; 95 CI, 2.26-28.7; p<0.005) and primary therapy with UFH (OR=19.2; 95 CI, 2.2-163.9; p=0.007).. Novel anticoagulant strategies might play a crucial role in critically ill cardiac surgery patients. In a propensity-matched population, results of the present study showed that primary bivalirudin anticoagulation may reduce bleeding complications and mortality.

Topics: Antithrombins; Cardiac Surgical Procedures; Critical Illness; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Hirudins; Humans; Injections, Intravenous; Italy; Male; Middle Aged; Peptide Fragments; Postoperative Complications; Propensity Score; Recombinant Proteins; Retrospective Studies; Survival Rate; Thrombosis

Bleeding complications after percutaneous coronary intervention (PCI) have been associated with higher short and long-term mortality. Bivalirudin has been shown to reduce bleeding complications in patients who underwent PCI; however, the impact of anemia on bleeding complications and long-term mortality has not been studied. A total of 11,991 patients who underwent PCI over a period of 8 years with bivalirudin as the primary antithrombotic agent were included. Anemia was defined according to the World Health Organization definition. Bleeding complications were prospectively collected. Survival analysis was performed using multivariable Cox proportional hazards models. Of the 11,991 patients, 4,815 patients (40%) had baseline anemia. Major bleeding occurred in 3.3% of patients with anemia compared with 0.7% of patients without anemia (p <0.001) driven largely by transfusion events. In the overall study population, major bleeding was a significant predictor of mortality (hazard ratio [HR] 1.4, 95% confidence interval [CI] 1.04 to 1.8, p = 0.027) at a mean follow-up of 2.6 years (interquartile range 1.4 to 3.5). In patients with anemia, major bleeding remained an independent predictor of mortality (HR 1.5, 95% CI 1.1 to 2.0, p = 0.008); however, in patients without anemia, it did not (HR 1.25, 95% CI 0.52 to 3.03, p = 0.62). In patients who underwent PCI with bivalirudin therapy, major bleeding is associated with early and long-term mortality, which is more pronounced in patients with baseline anemia.

Topics: Aged; Anemia, Hypochromic; Antithrombins; Female; Hemorrhage; Hirudins; Humans; Male; Peptide Fragments; Percutaneous Coronary Intervention; Postoperative Complications; Recombinant Proteins

Unfractionated heparin (UFH) is the anticoagulant of choice for extracorporeal membrane oxygenation (ECMO), but bivalirudin can be used as an alternative. The purpose of the present study is to investigate the existence of a heparin-like effect (HLE) during heparin-free ECMO.. This is a retrospective study on patients treated with ECMO and receiving bivalirudin as the sole anticoagulant. Thromboelastography (TEG) tests with and without heparinase were recorded during the ECMO duration. A total of 41 patients (22 pediatrics and 19 adults) treated with ECMO after cardiac surgery procedures and receiving only bivalirudin-based anticoagulation were studied. Based on the presence of a different reaction time (R-time) between the TEG test with heparinase or without heparinase we defined the presence of a HLE. Survival to hospital discharge, liver failure, sepsis, bleeding and transfusion rate were analyzed for association with HLE with univariate tests.. HLE was detected in 56.1% of the patients. R-times were significantly shorter in tests done with heparinase versus without heparinase during the first seven days on ECMO. Patients with HLE had a significantly (P = 0.046) higher rate of sepsis (30%) than patients without HLE (5.6%) at a Pearson's chi-square test.. A heparin-like effect is common during ECMO, and most likely due to a release of heparinoids from the glycocalyx and the mast cells, as a consequence of sepsis or of the systemic inflammatory reaction triggered by the contact of blood with foreign surfaces.

Topics: Adult; Anticoagulants; Cardiac Surgical Procedures; Child; Child, Preschool; Extracorporeal Membrane Oxygenation; Female; Hemorrhage; Hirudins; Humans; Infant; Infant, Newborn; Male; Partial Thromboplastin Time; Peptide Fragments; Postoperative Complications; Recombinant Proteins; Retrospective Studies; Thrombelastography; Time Factors

In primary angioplasty, bivalirudin is superior to treatment with heparin plus glycoprotein inhibitors for reducing cardiovascular events, although bivalirudin increases the risk of stent thrombosis. Our hypothesis is that the use of prasugrel plus bivalirudin in primary angioplasty would reduce stent thrombosis and cardiovascular events.. Consecutive patients with acute ST-segment elevation myocardial infarction who were treated by primary angioplasty within 12 hours of the onset of symptoms received bivalirudin plus clopidogrel (Group A) or bivalirudin plus prasugrel (Group B). We compared the groups using propensity score matching. The combined end-point was cardiac death, thrombosis, acute myocardial infarction, and cerebrovascular accident at 30 days.. We assessed 168 patients. The approach was preferentially radial (95.7%). No differences in baseline characteristics were observed between Groups A (n = 70) and B (n = 70). The total mortality and rate of major bleeding complications at 30 days were 0% for both of the groups. The rate of acute and subacute thrombosis was 4.3% in Group A and 0% in Group B (P = 0.08). We observed an increased rate of events in Group A (5.7%) versus Group B (0%) (P = 0.042).. The administration of bivalirudin plus prasugrel in primary percutaneous coronary intervention reduces cardiovascular effects compared to bivalirudin plus clopidogrel without increasing major bleeding complications during the first 30 days following primary angioplasty performed with a preferentially radial approach.

Topics: Angioplasty; Antithrombins; Clopidogrel; Cohort Studies; Drug Combinations; Female; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Piperazines; Postoperative Complications; Prasugrel Hydrochloride; Recombinant Proteins; Retrospective Studies; Thiophenes; Thrombosis; Ticlopidine

Thrombin inhibition is an important objective in the prevention and treatment of thrombosis. A new molecule, dabigatran etexilate or Pradaxa(®), has been recently licensed for thromboprophylaxis in major orthopedic surgery in several countries but not in the USA. In contrast, the FDA has approved it for prevention in patients with non-valvular atrial fibrillation. This new orally active anticoagulant is being developed for the treatment of venous thromboembolism and acute coronary syndromes in patients with non-valvular atrial fibrillation. Dabigatran is a reversible inhibitor of free thrombin and clot-bound thrombin. An oral thrombin inhibitor melagatran is no longer available due to hepatic toxicity. Several other thrombin inhibitors are used via parenteral administration: lepirudine and desirudine, bivalirudine and argatroban. They are mostly given to patients with heparin-induced thrombocytopenia (HIT). Bivalirudine is used for acute coronary syndrome in patients undergoing percutaneous interventions. The main pharmacologic characteristics of thrombin inhibitor agents are presented focusing on dabigatran etexilate and including the main results of clinical trials.

Topics: Anticoagulants; Antithrombins; Benzimidazoles; Contraindications; Dabigatran; Drug Interactions; Heparin; Hirudin Therapy; Hirudins; Humans; Orthopedic Procedures; Peptide Fragments; Postoperative Complications; Pyridines; Recombinant Proteins; Thrombocytopenia; Thrombosis; Venous Thrombosis

To compare the kaolin-activated coagulation time (K-ACT) to the MAX-ACT for monitoring anticoagulation with bivalirudin in patients undergoing hybrid off-pump coronary artery revascularization procedures.. A prospective, observational study.. A cardiac surgical operating room of a university-affiliated hospital.. Twelve patients undergoing off-pump coronary artery bypass graft surgery and percutaneous coronary intervention during the same procedure anticoagulated with bivalirudin to a target K-ACT of >300 seconds.. At baseline and at frequent intervals during anticoagulation, K-ACT and MAX-ACT assays were run contemporaneously, and the pairs of results were analyzed with descriptive statistics, by correlation analysis, and with Bland-Altman analysis.. The MAX-ACT and K-ACT assays were highly correlated, but the MAX-ACT assay consistently reported significantly lower ACT values compared with the K-ACT. The mean bias (K-ACT minus MAX-ACT) was 94 seconds (limits of agreement, 51-138 seconds).. To maximize patient safety, centers using bivalirudin for anticoagulation during cardiac surgical procedures need to be aware of the different performance characteristics of ACT assay subtypes.

Topics: Blood Coagulation; Coronary Artery Bypass, Off-Pump; Female; Hirudins; Humans; Male; Minimally Invasive Surgical Procedures; Partial Thromboplastin Time; Peptide Fragments; Postoperative Complications; Prospective Studies; Recombinant Proteins; Whole Blood Coagulation Time

Although bivalirudin compared with unfractionated heparin with glycoprotein IIb/IIIa inhibitors reduces bleeding and hospitalization costs in patients undergoing percutaneous coronary intervention (PCI), little is known about the economic impact of bivalirudin versus heparin alone and at what threshold of procedural bleeding risk bivalirudin would be considered cost-effective.. A validated model was used to predict risk of major bleeding for 81,628 National Cardiovascular Data Registry (NCDR) CathPCI Registry patients from 2004 to 2006 who received unfractionated heparin only. Costs were derived from multiple sources including wholesale acquisition costs (for drugs) and single-center data (for PCI-related complications). Based on ISAR-REACT 3, we assumed that bivalirudin would reduce the risk of major bleeding by 33% compared with unfractionated heparin alone. A Markov model was used to estimate lost life expectancy associated with a major bleed. Major bleeding was predicted to occur in 2.2% of patients. Bivalirudin for all patients was estimated to increase costs by $571 per patient, yielding cost-effectiveness ratios of $287,473 per bleeding event averted and $1,173,360 per quality-adjusted life-year gained. Bivalirudin was cost saving for patients with a predicted bleeding risk >20% (0.16% of CathPCI population). At willingness-to-pay thresholds of $50K and $100K per quality-adjusted life-year gained, bivalirudin was cost-effective for patients with a bleeding risk > or = 8% (2.5% patients) and > or = 5% (7.9% patients), respectively.. This decision-analytic modeling study demonstrates that for patients undergoing PCI, substitution of bivalirudin for unfractionated heparin monotherapy is projected to increase costs for virtually all patients and would be considered cost-effective for only a minority of patients with a high bleeding risk. From a policy standpoint, studies such as this, aimed at identifying the appropriate risk threshold for initiating treatment, may help in the development of informed guidelines for the use of expensive therapies.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Angioplasty; Cost-Benefit Analysis; Decision Support Techniques; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Postoperative Complications; Recombinant Proteins; Risk Adjustment

For patients undergoing elective percutaneous coronary intervention (PCI), procedural anticoagulation with bivalirudin was previously shown to significantly reduce bleeding complications at the cost of a modest increase in ischemic events compared with unfractionated heparin (UFH) and glycoprotein IIb/IIIa inhibitors (GPIs). However, the excess bleeding in patients treated with UFH and GPIs may have been caused by excessively high UFH doses and increased activated clotting times. This study sought to determine the bleeding risk of targeted low-dose UFH with GPIs compared with bivalirudin in patients undergoing elective PCI. Of 1,205 patients undergoing elective PCI, 602 underwent PCI with adjunctive UFH and GPIs with the UFH dose targeted to an activated clotting time of approximately 250 seconds, and 603 patients matched for baseline characteristics underwent PCI with bivalirudin. Outcomes were analyzed for major bleeding (hematocrit decrease >15%, gastrointestinal bleed, or major hematoma) and 6-month major adverse cardiac events (death, myocardial infarction, and target-lesion revascularization). The maximum activated clotting time achieved was 261.7 +/- 61.6 seconds in the UFH/GPI group and 355.4 +/- 66.6 in the bivalirudin group (p <0.001). In-hospital major bleeding rates were similar between groups (1.8% UFH/GPI vs 1.7% bivalirudin; p = 0.83), as were transfusion requirements (1.2% UFH/GPI vs 0.5% bivalirudin; p = 0.61). The 6-month major adverse cardiac event rate was also similar between groups (9.5% UFH/GPI vs 9.0% bivalirudin; p = 0.81). In conclusion, there were no significant differences in major bleeding and 6-month major adverse cardiac events for patients undergoing elective PCI treated with targeted low-dose UFH and GPIs compared with those treated with bivalirudin.

Topics: Angina Pectoris; Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Complications; Recombinant Proteins; Risk Assessment; Risk Factors; Treatment Outcome

Anticoagulation with unfractionated heparin has been the standard of care for more than a half-century for patients undergoing cardiac surgery. The risk of heparin-induced adverse reactions dictates the need for a safe and effective alternative, particularly in off-pump coronary artery bypass (OPCAB) surgery, an approach associated with a perioperative prothrombotic condition that may negatively influence graft patency. Between March 2003 and January 2005, 243 consecutive patients underwent OPCAB with bivalirudin (0.75 mg/kg bolus with 1.75 mg/kg per hour infusion). There were 171 men (70.4%) and 72 women (29.6%). The mean age was 64.9 +/- 10.9 years (age range 32-88 years). There were 147 patients (60.5%) with 3-vessel disease; 46 (18.9%) had substantial (>50%) stenosis of the left main coronary artery; 104 (42.8%) had a moderately reduced (0.30 to 0.50) ejection fraction; and 9 (3.7%) had a severely reduced (<0.30%) ejection fraction. Five patients (2.1%) required conversion to cardiopulmonary bypass and subsequently received heparin. Postoperative complications included perioperative myocardial infarction in 6 patients (2.5%), stroke in 3 (1.2%), prolonged ventilation in 4 (1.6%), reoperation for bleeding in 3 (1.2%), renal insufficiency in 14 (5.8%), atrial fibrillation in 26 (10.7%), low cardiac output in 3 (1.2%), and deep sternal infection in 1 (0.4%). Blood products were used in 117 patients (48.1%). The overall hospital mortality rate was 0.4% (1 of 243). Bivalirudin is a safe and effective anticoagulant that may be routinely used as an alternative to heparin and protamine in patients undergoing OPCAB. This is evidenced by low hospital mortality and morbidity rates. Further follow-up is warranted to discern the influence of bivalirudin on long-term clinical outcomes.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Coronary Artery Bypass; Coronary Artery Bypass, Off-Pump; Female; Fibrinolytic Agents; Health Status Indicators; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Postoperative Complications; Recombinant Proteins; Retrospective Studies; Risk Factors; Thrombin; Treatment Outcome

Rotational atherectomy is associated with a high incidence of periprocedural myonecrosis. Glycoprotein (GP) IIb/IIIa inhibitors have been demonstrated to be particularly effective in this population in reducing periprocedural myocardial infarction. While bivalirudin-based therapy has emerged as an attractive alternative to heparin in patients undergoing contemporary percutaneous coronary intervention, it is unclear if such a strategy is safe in patients undergoing rotational atherectomy.. We analyzed all patients undergoing rotational atherectomy at our institution from 2001 to 2004, and compared periprocedural outcome among those treated with a bivalirudin-based regimen compared to those treated with a heparin-based regimen.. A total of 253 patients were treated with rotational atherectomy during this period. Bivalirudin-based therapy was used in 56 patients, while the remainder were treated with a heparin-based approach. Patients treated with heparin were significantly more likely to be treated with GP IIb/IIIa inhibitors (91% vs 25%; p = 0.001). There was no difference in the two groups with respect to gender, diabetes, peripheral vascular disease or incidence of renal dysfunction. While there was no statistical difference in the incidence of any myonecrosis (32% versus 34%; p = 0.87), the incidence of creatine kinase-MB was greater than 3 times the upper limit of normal (ULN) (14.1% versus 5.7%; p = 0.15), or CK-MB >5 times the ULN (7.3% versus 1.9%) was nonsignificantly lower in the group treated with bivalirudin.. Bivalirudin-based therapy can be safely used in selected patients undergoing rotational atherectomy. Further studies are warranted to confirm our findings.

Topics: Aged; Aged, 80 and over; Atherectomy, Coronary; Coronary Restenosis; Coronary Stenosis; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Platelet Aggregation Inhibitors; Postoperative Complications; Prospective Studies; Radiography; Recombinant Proteins; Registries; Risk Assessment; Survival Analysis; Treatment Outcome

To perform a cost-effectiveness analysis comparing three treatment approaches during nonurgent percutaneous coronary intervention (PCI): bivalirudin with provisional glycoprotein (GP) IIb-IIIa inhibitor therapy, unfractionated heparin (UFH) with eptifibatide, and UFH with abciximab.. Literature-based decision model from an institutional perspective.. Patient data from the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 study and three other randomized controlled trials that included UFH and routine GP IIb-IIIa inhibitor (eptifibatide or abciximab) therapy. All included studies were comparable based on patient population, procedural techniques, and general treatment approaches.. We included patient populations undergoing contemporary nonurgent PCI to identify probabilities of success or complications (myocardial infarction, urgent revascularization, thrombocytopenia, and major or minor bleeding at 30 days). Costs were assigned to each outcome by incorporating diagnosis-related group-- and/or Current Procedural Terminology--associated costs, institutional drug acquisition costs, and unit replacement costs of platelets and red blood cells. In the base-case analysis, the use of bivalirudin with provisional GP IIb-IIIa inhibitor therapy dominated the UFH and planned GP IIb-IIIa inhibitor approach: UFH with eptifibatide was 74 US dollars more expensive and 1.2% less effective, and UFH with abciximab was 777 US dollars more expensive and 2.3% less effective. Sensitivity analyses indicated that the model results were robust, but also revealed that bivalirudin lost its cost-effectiveness, resulting in UFH with eptifibatide becoming more cost-effective, when two or more vials of bivalirudin were necessary in greater than 27% of cases or when the use of provisional GP IIb-IIIa inhibitor therapy exceeded 20%.. This analysis indicates that bivalirudin with provisional GP IIb-IIIa inhibitor therapy is the most cost-effective antithrombotic treatment strategy in nonurgent PCI when its use and dosing are consistent with the REPLACE-2 trial.

Topics: Abciximab; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Antithrombins; Coronary Disease; Cost-Benefit Analysis; Databases, Factual; Decision Support Techniques; Drug Costs; Eptifibatide; Fibrinolytic Agents; Heparin; Hirudins; Humans; Immunoglobulin Fab Fragments; Peptide Fragments; Peptides; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Complications; Randomized Controlled Trials as Topic; Recombinant Proteins; Treatment Outcome

Topics: Angina, Unstable; Angioplasty, Balloon, Coronary; Antithrombins; Coronary Circulation; Eptifibatide; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Peptides; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Complications; Postoperative Hemorrhage; Recombinant Proteins

Bivalirudin, a direct thrombin inhibitor, has recently emerged as a promising option for anti-coagulation during cardiopulmonary bypass in patients who cannot receive heparin. There is limited experience with the use of bivalirudin in children. We present the case of a child with heparin-induced thrombocytopenia with thrombosis (HIT Type II) who underwent successful orthotopic cardiac transplantation using bivalirudin as the primary anti-coagulant for cardiopulmonary bypass.

Topics: Anticoagulants; Cardiopulmonary Bypass; Child, Preschool; Dose-Response Relationship, Drug; Female; Heart Transplantation; Heparin; Hirudins; Humans; Peptide Fragments; Postoperative Complications; Recombinant Proteins; Thrombin; Thrombocytopenia; Thrombosis

Traditionally, unfractionated heparin is used to prevent thrombotic complications in peripheral interventions. The purpose of this study is to evaluate the use of bivalirudin as the anticoagulant agent for peripheral interventions.. A retrospective analysis of 108 patients who underwent 110 peripheral interventions between January 2002 and January 2004 and received bivalirudin as the sole anticoagulation agent was conducted at Baptist Cardiac and Vascular Institute. Interventions were performed in the following areas: iliac, femoropopliteal, and distal (n = 55), carotid (n = 31), vertebral (n = 1), renal (n = 14), aorta (n = 7), and subclavian (n = 2). The following procedural and clinical endpoints were examined: death, requirement of urgent surgery or surgery during the same admission, urgent percutaneous revascularization in the same treated vessel, thrombotic or embolic events, bleeding events, and groin complications.. A total of 266 lesions were dilated in 185 arteries. There were no procedural mortalities, procedural success was 99.1%, and the complication rate was 3.6%. There was one embolic stroke (0.9%), one thrombosis (0.9%), and two groin hematomas (1.8%). No patient required urgent surgery or reintervention in the same treated vessel. No complications were noted at 7 days after the procedure. There were two interventions by postprocedure day 30: toe amputation and groin debridement.. Bivalirudin is a safe alternative to unfractionated heparin as the anticoagulation agent in peripheral interventions. This study shows that the complication profile is comparable to other bivalirudin studies. Bivalirudin is effective, easy to use, and is associated with few bleeding complications.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aorta; Carotid Artery, Common; Female; Femoral Artery; Florida; Follow-Up Studies; Hirudins; Humans; Iliac Artery; Length of Stay; Male; Middle Aged; Peptide Fragments; Peripheral Vascular Diseases; Popliteal Artery; Postoperative Complications; Recombinant Proteins; Renal Artery; Retrospective Studies; Subclavian Artery; Treatment Outcome; Vascular Surgical Procedures; Vertebral Artery

Subacute thrombosis is an infrequent but potentially life-threatening complication of percutaneous coronary intervention (PCI) that has received much attention in association with drug-eluting stent (DES) deployment. We performed a retrospective case record review of 186 patients receiving PCI with DES placement at our facility. Patients received either bivalirudin (n=115) or heparin (n=71) as the foundation anticoagulant, with additional antiplatelet therapy as warranted. Two subacute thrombosis complications occurred and are described in detail. There were no deaths, major bleeding episodes or other significant complications. We report our findings and conclude that the addition of a glycoprotein IIb/IIIa inhibitor does not eliminate the risk of subacute thrombosis and that bivalirudin appears to provide effective anticoagulation for patients undergoing PCI with placement of a DES.

Topics: Adult; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Anticoagulants; Blood Vessel Prosthesis Implantation; Drug Delivery Systems; Drug Therapy, Combination; Female; Heparin; Hirudins; Humans; Infusions, Intravenous; Male; Middle Aged; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Complications; Recombinant Proteins; Retrospective Studies; Stents; Thrombosis

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Disease; Cost-Benefit Analysis; Embolism; Heparin; Hirudins; Hospitalization; Humans; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Complications; Recombinant Proteins; Saphenous Vein

Heparin-associated thrombocytopenia is a serious medical problem, especially when the patient requires continued anticoagulation. Hirulog is an immediate-acting intravenous anticoagulant that can be substituted for heparin. A new use of Hirulog in the treatment of life-threatening heparin-associated thrombocytopenia with thrombosis (HATT) is presented. Two patients suffering from the HATT syndrome were successfully treated with Hirulog to prevent further thrombosis. A third patient had developed heparin-associated thrombocytopenia after coronary artery bypass surgery in the past and was subsequently treated with Hirulog during a peripheral angioplasty procedure. Hirulog was an effective and predictable anticoagulant for these patients and was free from adverse effects.

Topics: Aged; Angioplasty, Balloon; Anticoagulants; Coronary Artery Bypass; Coronary Thrombosis; Heparin; Hirudin Therapy; Hirudins; Humans; Injections, Intravenous; Male; Peptide Fragments; Postoperative Complications; Recombinant Proteins; Thrombin; Thrombocytopenia

Hirulog, a thrombin-specific inhibitor, has shown efficacy in reducing arterial thrombosis in patients treated with aspirin who require angioplasty or have unstable angina. In this study, the effect of hirulog on reducing deposition of indium 111-labeled platelets was assessed in a surgical model of aspirin-treated rats undergoing carotid endarterectomy.. Animals were randomly assigned to one of five groups: control (no aspirin or hirulog); aspirin alone (10 mg/kg); aspirin plus low-dose hirulog (0.2 mg/kg bolus followed by 0.5 mg/kg/hr); aspirin plus medium-dose hirulog (0.4 mg/kg bolus followed by 1.0 mg/kg/hr); or aspirin plus high-dose hirulog (0.6 mg/kg bolus followed by 1.5 mg/kg/hr). Hirulog was infused before surgery and continued until termination of the experiment 30 minutes after endarterectomy.. Platelet deposition in rats receiving aspirin alone was reduced by 19% +/- 23% SE (p = 0.26) compared with controls. Deposition in aspirin-treated groups receiving low-, medium-, and high-dose hirulog decreased in a dose-dependent manner by 37% +/- 20% (p = 0.048), 44% +/- 19% (p = 0.061), and 56% +/- 13% (p = 0.022), respectively. As the dose of hirulog was increased, the plasma hirulog levels and activated partial thromboplastin time ratios (final:initial) also increased in a dose-dependent manner. The mean plasma hirulog levels ranged from 0.74 +/- 0.08 micrograms/ml in the low-dose hirulog group to 2.55 +/- 0.08 micrograms/ml in the high-dose hirulog group, and the corresponding activated partial thromboplastin time ratios were 1.5 +/- 0.12 (p = 0.001) and 3.3 +/- 0.63 (p = 0.001). Bleeding was easily controlled by local hemostatic measures for all experimental groups.. Hirulog causes significant decrease in 111In-labeled platelet deposition in aspirin-treated rats subjected to microsurgical endarterectomy at doses that allow surgical hemostasis to be easily established.

Topics: Animals; Aspirin; Blood Platelets; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; Endarterectomy, Carotid; Hirudin Therapy; Hirudins; Male; Peptide Fragments; Postoperative Complications; Random Allocation; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Thrombin; Thrombosis