hirudin and Coronary-Stenosis

This chapter about antithrombotic therapy during percutaneous coronary intervention (PCI) is part of the seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading, see Guyatt et al, CHEST 2004;126:179S-187S). Among the key recommendations in this chapter are the following: For patients undergoing PCI, we recommend pretreatment with aspirin, 75 to 325 mg (Grade 1A). For long-term treatment after PCI, we recommend aspirin, 75 to 162 mg/d (Grade 1A). For long-term treatment after PCI in patients who receive antithrombotic agents such as clopidogrel or warfarin, we recommend lower-dose aspirin, 75 to 100 mg/d (Grade 1C+). For patients who undergo stent placement, we recommend the combination of aspirin and a thienopyridine derivative (ticlopidine or clopidogrel) over systemic anticoagulation therapy (Grade 1A). We recommend clopidogrel over ticlopidine (Grade 1A). For all patients undergoing PCI, particularly those undergoing primary PCI, or those with refractory unstable angina or other high-risk features, we recommend use of a glycoprotein (GP) IIb-IIIa antagonist (abciximab or eptifibatide) [Grade 1A]. In patients undergoing PCI for ST-segment elevation MI, we recommend abciximab over eptifibatide (Grade 1B). In patients undergoing PCI, we recommend against the use of tirofiban as an alternative to abciximab (Grade 1A). In patients after uncomplicated PCI, we recommend against routine postprocedural infusion of heparin (Grade 1A). For patients undergoing PCI who are not treated with a GP IIb-IIIa antagonist, we recommend bivalirudin over heparin during PCI (Grade 1A). In PCI patients who are at low risk for complications, we recommend bivalirudin as an alternative to heparin as an adjunct to GP IIb-IIIa antagonists (Grade 1B). In PCI patients who are at high risk for bleeding, we recommend that bivalirudin over heparin as an adjunct to GP IIb-IIIa antagonists (Grade 1B). In patients who undergo PCI with no other indication for systemic anticoagulation therapy, we recommend against routine use of vitamin K antagonists after PCI (Grade 1A).

Topics: Abciximab; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Aspirin; Clopidogrel; Contraindications; Coronary Restenosis; Coronary Stenosis; Drug Therapy, Combination; Evidence-Based Medicine; Fibrinolytic Agents; Heparin; Hirudins; Humans; Immunoglobulin Fab Fragments; Peptide Fragments; Practice Guidelines as Topic; Pyridines; Recombinant Proteins; Risk Assessment; Stents; Ticlopidine

Whether prasugrel plus bivalirudin is a superior strategy to unfractionated heparin plus clopidogrel in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) has never been assessed in specifically designed randomized trials.. The Bavarian Reperfusion Alternatives Evaluation (BRAVE) 4 study is an investigator-initiated, randomized, open-label, multicentre trial, designed to test the hypothesis that in STEMI patients with planned primary PCI a strategy based on prasugrel plus bivalirudin is superior to a strategy based on clopidogrel plus heparin in terms of net clinical outcome. Owing to slow recruitment, the trial was stopped prematurely after enrolment of 548 of 1240 planned patients. At 30 days, the primary composite endpoint of death, myocardial infarction, unplanned revascularization of the infarct related artery, stent thrombosis, stroke, or bleeding was observed in 42 patients (15.6%) randomized to prasugrel plus bivalirudin and 40 patients (14.5%) randomized to clopidogrel plus heparin [relative risk, 1.09; one-sided 97.5% confidence interval (CI) 0-1.79, P = 0.680]. The composite ischaemic endpoint of death, myocardial infarction, unplanned revascularization of the infarct-related artery, stent thrombosis, or stroke occurred in 13 patients (4.8%) in the prasugrel plus bivalirudin group and 15 patients (5.5%) in the clopidogrel plus heparin group (relative risk, 0.89; 95% CI 0.40-1.96, P = 0.894). Bleeding according to the HORIZONS-AMI definition was observed in 38 patients (14.1%) in the prasugrel plus bivalirudin group and 33 patients (12.0%) in the clopidogrel plus heparin group (relative risk, 1.18; 95% CI 0.74-1.88, P = 0.543). Results were consistent across various subgroups of patients.. In this randomized trial of STEMI patients, we were unable to demonstrate significant differences in net clinical outcome between prasugrel plus bivalirudin and clopidogrel plus heparin. Neither the composite of ischaemic complications nor bleeding were favourably affected by prasugrel plus bivalirudin compared with a regimen of clopidogrel plus unfractionated heparin. However, the results must be interpreted in view of the premature termination of the trial.. Unique identifier NCT00976092 (www.clinicaltrials.gov).

Topics: Aged; Anticoagulants; Clopidogrel; Coronary Angiography; Coronary Stenosis; Drug Therapy, Combination; Early Termination of Clinical Trials; Heparin; Hirudins; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Recombinant Proteins; Thiophenes; Ticlopidine; Treatment Outcome

Bivalirudin, with selective use of glycoprotein (GP) IIb/IIIa inhibitor agents, is an accepted standard of care in primary percutaneous coronary intervention (PPCI). We aimed to compare antithrombotic therapy with bivalirudin or unfractionated heparin during this procedure.. In our open-label, randomised controlled trial, we enrolled consecutive adults scheduled for angiography in the context of a PPCI presentation at Liverpool Heart and Chest Hospital (Liverpool, UK) with a strategy of delayed consent. Before angiography, we randomly allocated patients (1:1; stratified by age [<75 years vs ≥75 years] and presence of cardiogenic shock [yes vs no]) to heparin (70 U/kg) or bivalirudin (bolus 0·75 mg/kg; infusion 1·75 mg/kg per h). Patients were followed up for 28 days. The primary efficacy outcome was a composite of all-cause mortality, cerebrovascular accident, reinfarction, or unplanned target lesion revascularisation. The primary safety outcome was incidence of major bleeding (type 3-5 as per Bleeding Academic Research Consortium definitions). This study is registered with ClinicalTrials.gov, number NCT01519518.. Between Feb 7, 2012, and Nov 20, 2013, 1829 of 1917 patients undergoing emergency angiography at our centre (representing 97% of trial-naive presentations) were randomly allocated treatment, with 1812 included in the final analyses. 751 (83%) of 905 patients in the bivalirudin group and 740 (82%) of 907 patients in the heparin group had a percutaneous coronary intervention. The rate of GP IIb/IIIa inhibitor use was much the same between groups (122 patients [13%] in the bivalirudin group and 140 patients [15%] in the heparin group). The primary efficacy outcome occurred in 79 (8·7%) of 905 patients in the bivalirudin group and 52 (5·7%) of 907 patients in the heparin group (absolute risk difference 3·0%; relative risk [RR] 1·52, 95% CI 1·09-2·13, p=0·01). The primary safety outcome occurred in 32 (3·5%) of 905 patients in the bivalirudin group and 28 (3·1%) of 907 patients in the heparin group (0·4%; 1·15, 0·70-1·89, p=0·59).. Compared with bivalirudin, heparin reduces the incidence of major adverse ischaemic events in the setting of PPCI, with no increase in bleeding complications. Systematic use of heparin rather than bivalirudin would reduce drug costs substantially.. Liverpool Heart and Chest Hospital, UK National Institute of Health Research, The Medicines Company, AstraZeneca, The Bentley Drivers Club (UK).

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Stenosis; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Heparin; Hirudins; Humans; Infusions, Intravenous; Injections, Subcutaneous; Male; Middle Aged; Peptide Fragments; Recombinant Proteins; Severity of Illness Index; Survival Rate; Time Factors; Treatment Outcome; United Kingdom

Concomitant antithrombotic therapy is essential for the prevention of ischaemic events in percutaneous coronary intervention (PCI) and stenting. With new anticoagulant medications being developed and applied in PCI, this raises the question of possible interactions with platelet and leukocyte activation. We therefore sought to investigate the influence of bivalirudin and heparin in platelet and leukocyte activation in patients undergoing elective PCI. Forty-six patients were recruited consecutively in the setting of the Intracoronary Stenting and Antithrombotic Regimen-Rapid Early Action for Coronary Treatment (ISAR-REACT)-3 trial and were randomly assigned to receive either unfactionated heparin or bivalirudin during elective PCI. Surface expression of CD62P (P-Selectin), CD42b (GPIbalpha), CD40L, PAC-1 on circulating platelets and CD11b, CD14 and CD15 on circulating leukocytes were evaluated by flow cytometry. Cytokine levels of IL-12p70, tumour necrosis factor (TNF), IL-8, IL-6, IL-1beta and IL-10 were determined by cytometric bead array. Platelet surface expression of PAC-1, P-Selectin and GPIbalpha was significantly reduced after PCI in patients receiving bivalirudin as compared to heparin. Similarly, CD11b expression on CD14+ monocytes was diminished after bivalirudin. However, no differences were observed in cytokine levels between the bivalirudin and the heparin group, before or after PCI. In conclusion, our data suggest that bivalirudin may reduce platelet and monocyte activation in patients undergoing elective PCI. Thereby, bivalirudin might reduce periinterventional thrombotic complications.

Topics: Adult; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Anticoagulants; Antigens, CD; Coronary Angiography; Coronary Stenosis; Cytokines; Double-Blind Method; Female; Fibrinolytic Agents; Heparin; Hirudins; Humans; Male; Middle Aged; Monocytes; Peptide Fragments; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Membrane Glycoproteins; Prospective Studies; Recombinant Proteins; Thrombosis; Time Factors; Treatment Outcome

OBJECTIVES The objective of this study was to determine whether adjunctive therapy during percutaneous coronary intervention (PCI) affects markers of systemic inflammation or platelet activation. Despite different mechanisms of action, direct-thrombin inhibition with bivalirudin during PCI provided similar protection from periprocedural and chronic ischemic complications as compared with unfractionated heparin (UFH) plus planned use of GPIIb/IIIa antagonists in the REPLACE-2 and ACUITY trials.. Patients undergoing nonurgent PCI of a native coronary artery were randomized to receive adjunctive therapy with bivalirudin or UFH+eptifibatide. Interleukin (IL)-6 and C-reactive protein (CRP) transiently increased in both groups after PCI. In the UFH+eptifibatide, but not the bivalirudin group, myeloperoxidase (MPO) levels were elevated 2.3-fold above baseline (P=0.004) immediately after PCI. In an in vitro assay, heparin and to a lesser extent enoxaparin, but not bivalirudin or eptifibatide, stimulated MPO release from and binding to neutrophils and neutrophil activation. A mouse model of endoluminal femoral artery denudation was used to investigate further the importance of MPO in the context of arterial injury.. Adjuvant therapy during PCI may have undesired effects on neutrophil activation, MPO release, and systemic inflammation.

Topics: Adult; Aged; Analysis of Variance; Angioplasty, Balloon, Coronary; Biomarkers; Combined Modality Therapy; Coronary Stenosis; Dose-Response Relationship, Drug; Drug Administration Schedule; Eptifibatide; Female; Follow-Up Studies; Heparin, Low-Molecular-Weight; Hirudins; Humans; Male; Middle Aged; Neutrophils; Peptide Fragments; Peptides; Peroxidase; Probability; Recombinant Proteins; Reference Values; Severity of Illness Index; Treatment Outcome

Thrombus formation after stent deployment has been linked to the use of heparin and of antithrombotic agents, such as bivalirudin, during percutaneous coronary intervention. Fluoroscopy has been used to identify stent thrombosis, typically after patients become symptomatic. We describe our use of optical coherence tomography to diagnose and evaluate intraprocedural stent thrombosis in a 68-year-old man who was given bivalirudin just before a percutaneous coronary procedure. This imaging method enabled immediate therapeutic intervention.

Topics: Abciximab; Aged; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Antithrombins; Coronary Stenosis; Coronary Thrombosis; Coronary Vessels; Hirudins; Humans; Immunoglobulin Fab Fragments; Male; Peptide Fragments; Platelet Aggregation Inhibitors; Predictive Value of Tests; Recombinant Proteins; Stents; Tomography, Optical Coherence; Treatment Outcome

Topics: Angioplasty, Balloon, Coronary; Coronary Stenosis; Female; Heparin; Hirudins; Humans; Male; Peptide Fragments; Radiography; Recombinant Proteins

Topics: Angioplasty, Balloon, Coronary; Coronary Stenosis; Female; Heparin; Hirudins; Humans; Male; Peptide Fragments; Radiography; Recombinant Proteins

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

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

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

A recent large-scale, randomized trial demonstrated the noninferiority of a strategy of bivalirudin with provisional glycoprotein (GP) IIb/IIIa inhibition compared with routine GP IIb/IIIa inhibition. There is a paucity of outcome data with bivalirudin use in the setting of real-world experience. We evaluated 6,996 patients who underwent percutaneous coronary intervention between January 2001 and December 2004 to compare early and late outcomes with a bivalirudin-based antithrombotic regimen with those with a heparin-based regimen. Propensity adjustment was performed to correct for baseline differences in patient characteristics. Bivalirudin-based therapy was used in 1,070 patients, heparin only in 801 patients, and heparin plus GP IIb/IIIa inhibitors in 5,125 patients. Compared with patients who received heparin or those who received heparin plus GP IIb/IIIa inhibitors, patients who received bivalirudin had lower incidences of bleeding (blood transfusion rate 1.7% vs 4.0%, p <0.001) and periprocedural myonecrosis (creatine kinase-MB >5 times the upper limit of normal 2.7% vs 4.3%, p = 0.016). Differences in bleeding end points remained significant after adjusting for the propensity to receive bivalirudin, but there was no difference in ischemic events. There was no difference in unadjusted long-term survival rate (log-rank test p = 0.46, total number of deaths 412, mean follow-up 17 months) or in propensity-adjusted long-term survival rate (hazard ratio 1.37, 95% confidence interval 0.90 to 2.08, p = 0.14). Compared with heparin with or without GP IIb/IIIa inhibition, the use of bivalirudin in a large consecutive patient registry at a tertiary care center was associated with fewer bleeding events and no evident increase in the incidence of ischemic complications.

Topics: Aged; Angioplasty, Balloon, Coronary; Cohort Studies; Coronary Restenosis; Coronary Stenosis; Creatine Kinase; Creatine Kinase, MB Form; Drug Therapy, Combination; Female; Fibrinolytic Agents; Follow-Up Studies; Hemorrhage; Heparin; Hirudins; Humans; Isoenzymes; Male; Middle Aged; Myocardial Infarction; Ohio; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Prospective Studies; Recombinant Proteins; Survival Analysis; Treatment Outcome

Bivalirudin is shown to be a competent substitute for heparin in percutaneous coronary intervention (PCI). The safety and efficacy of bivalirudin in patients undergoing PCI and vascular brachytherapy (VBT) are not known. This study aimed to assess the safety and efficacy of bivalirudin as a single antithrombotic agent in patients undergoing PCI and VBT.. A total of 152 patients enrolled in the Brachytherapy and Bivalirudin Evaluation Study underwent PCI and VBT with either gamma (n = 8) or beta radiation (n = 144). The main outcome measures were in-hospital events and 30-day clinical outcomes. All patients were treated with bivalirudin (0.75 mg/kg bolus and 1.75 mg/kg per hour infusion for beta radiation, 1 mg/kg bolus and 2.5 mg/kg per hour infusion for gamma radiation) as a single antithrombotic agent during the entire procedure.. Baseline clinical and angiographic characteristics were similar between the 2 groups. More than 90% of the patients received beta radiation. In-hospital events showed a higher prevalence of acute procedural intracoronary thrombosis in patients treated with gamma- vs beta radiation (25% vs. 0.7%, P < .001). Thirty-day outcomes including death, Q-wave, and non-Q-wave myocardial infarctions, subacute stent thromboses, and repeat revascularizations were similar in both groups.. Bivalirudin, as a single antithrombotic agent during PCI and VBT with beta emitters, may be used safely, but its use in the setting of PCI and gamma radiation may not be acceptable due to an increased incidence of acute procedural intracoronary thrombosis.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Brachytherapy; Coronary Stenosis; Female; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Recombinant Proteins; Thrombosis

Topics: Adult; Angioplasty, Balloon, Coronary; Antithrombins; Cardiac Catheterization; Coronary Circulation; Coronary Stenosis; Hirudins; Humans; Intraoperative Care; Male; Myocardial Infarction; Peptide Fragments; Recombinant Proteins