thienopyridine and bivalirudin

In 2006, the American College of Cardiology, American Heart Association, and Society for Cardiovascular Interventions published the 2005 update of the evidence-based guidelines for the treatment of patients undergoing percutaneous coronary intervention (PCI). Together with procedural recommendations, these guidelines for percutaneous coronary intervention provide clinicians with guidance in the appropriate use of adjunctive pharmacologic therapy in patients undergoing PCI. However, there remain substantial variations in practice among clinicians and within and across institutions. Furthermore, the guidelines (being a static document) cannot incorporate additional evidence that has accumulated since their publication. Several landmark trials, notably Intracoronary Stenting and Antithrombotic Regimen-Rapid Early Action for Coronary Treatment (ISAR-REACT 2) and Acute Catheterization and Urgent Intervention Triage strategY (ACUITY), have added substantially to the knowledge base about pharmacologic therapy since publication of the guidelines. This article is therefore intended to discuss implementation into clinical practice of the revised guidelines for antiplatelet and antithrombotic pharmacologic therapy during PCI and to evaluate recent clinical evidence and make recommendations for revision of the guidelines incorporating the outcomes of recently completed trials.

Topics: American Heart Association; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Clopidogrel; Combined Modality Therapy; Coronary Disease; Drug-Eluting Stents; Hirudins; Humans; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Practice Guidelines as Topic; Pyridines; Recombinant Proteins; Societies, Medical; Thrombolytic Therapy; Ticlopidine; United States

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

We assessed the impact of smoking on outcomes in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention using alternative antithrombotic regimens and stent types. In the HORIZONS-AMI trial 3,602 patients were randomly assigned to unfractionated heparin (UFH) plus a glycoprotein IIb/IIIa inhibitor (GPI) or bivalirudin alone and paclitaxel-eluting stents or bare-metal stents. Compared to nonsmokers, smokers had significantly lower rates of mortality and major bleeding at 30 days and at 1 year; however, the differences were no longer significant after covariate adjustment. Smoking was associated with increased rates of definite/probable stent thrombosis (ST) at 1 year (adjusted RR 1.99, 95% confidence interval 1.28 to 3.10) mainly because of a higher rate of late ST after paclitaxel-eluting stent implantation (1.9% vs 0.4%, p = 0.0006). In smokers bivalirudin monotherapy compared to UFH plus a GPI was associated with lower mortality at 30 days (0.5% vs 2.2%, p = 0.002) and at 1 year (1.8% vs 4.0%, p = 0.008). No decrease in mortality was seen with bivalirudin in nonsmokers. Major bleeding was significantly decreased with bivalirudin regardless of smoking status (smokers 3.7% vs 8.9%, p <0.0001; nonsmokers 6.5% vs 9.6%, p = 0.01). In conclusion, in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention, smoking is an independent predictor of definite/probable ST at 1 year. Bivalirudin monotherapy compared to UFH plus a GPI decreased major bleeding regardless of smoking status but may have different effects on individual components of ischemic events.

Topics: Aged; Angioplasty, Balloon, Coronary; Antithrombins; Coronary Angiography; Coronary Restenosis; Coronary Thrombosis; Drug Therapy, Combination; Drug Utilization; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Paclitaxel; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Pyridines; Recombinant Proteins; Smoking; Stents

Timely and appropriate use of antiplatelet and anticoagulant therapies has been shown to improve outcomes among ST-segment elevation myocardial infarction (STEMI) patients but has not been well described in patients transferred for primary percutaneous coronary intervention (PCI).. We examined 16,801 (26%) transfer and 47,329 direct-arrival STEMI patients treated with primary PCI at 441 Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With The Guidelines hospitals. Medication use was compared between transfer and direct-arrival patients to determine if these therapies were delayed or dosed in excess.. Although transfer patients were more likely to receive antiplatelet and anticoagulant therapies before catheterization, they had longer delays to initiation of heparin (35 vs. 25 minutes), clopidogrel (119 vs. 84 minutes), and glycoprotein IIb/IIIa inhibitor (107 vs. 60 minutes, P < .0001 for both). Administration of low-molecular-weight heparin and glycoprotein IIb/IIIa inhibitor at the STEMI-referring hospital was associated with longer delays to reperfusion compared with deferred administration at the STEMI-receiving hospital, whereas early use of unfractionated heparin was not. Among treated patients, those transferred were more likely to receive excess heparin dosing (adjusted odds ratio [OR] 1.28 [95% CI 1.04-1.58] for unfractionated heparin, adjusted OR 1.54 [95% CI 1.09-2.18] for low-molecular-weight heparin) and are associated with higher risks of major bleeding complications (adjusted OR 1.10, 95% CI 1.03-1.17).. ST-segment elevation myocardial infarction patients transferred for primary PCI in community practice are at risk for delayed and excessively dosed antithrombotic therapy, highlighting the need for continued quality improvement to maximize the appropriate use of these important adjunctive therapies.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Clopidogrel; Cohort Studies; Early Medical Intervention; Female; Guideline Adherence; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Patient Transfer; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Practice Guidelines as Topic; Pyridines; Recombinant Proteins; Retrospective Studies; Ticlopidine; Time-to-Treatment

This study sought to assess the cost-effectiveness of bivalirudin versus heparin plus glycoprotein IIb/IIIa inhibitor (GPI) in thienopyridine-treated non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients undergoing early or urgent invasive management, from a United Kingdom National Health Service perspective.. A decision-analytic model with lifelong time horizon was populated with event risks and resource use parameters derived from the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial raw data. In a parallel analysis, key comparator strategy inputs came from Global Registry of Acute Coronary Events (GRACE) patients enrolled in the United Kingdom. Upstream and catheter laboratory-initiated GPI were assumed to be tirofiban and abciximab, respectively. Life expectancy of first-year survivors, unit costs, and health-state utilities came from United Kingdom sources. Costs and effects were discounted at 3.5%. Incremental cost-effectiveness ratios (ICERs) were expressed as cost per quality-adjusted life year (QALY) gained.. Higher acquisition costs for bivalirudin were partially offset by lower hospitalization and bleeding costs. In the ACUITY-based analysis, per-patient lifetime costs in the bivalirudin and heparin plus GPI strategies were £10,903 and £10,653, respectively. Patients survived 10.87 and 10.82 years on average, corresponding to 5.96 and 5.93 QALYs and resulting in an ICER of £9,906 per QALY gained. The GRACE-based ICER was £12,276 per QALY gained. In probabilistic sensitivity analysis, 72.1% and 67.0% of simulation results were more cost-effective than £20,000 per QALY gained, in the ACUITY-based and GRACE-based analyses, respectively. Additional scenario analyses implied that greater cost-effectiveness may be achieved in actual clinical practice.. Treating NSTE-ACS patients undergoing invasive management with bivalirudin is likely to represent a cost-effective option for the United Kingdom, when compared with the current practice of using heparin and a GPI.

Topics: Abciximab; Acute Coronary Syndrome; Antibodies, Monoclonal; Anticoagulants; Cost-Benefit Analysis; Decision Trees; Drug Therapy, Combination; Female; Health Care Costs; Heparin; Hirudins; Humans; Immunoglobulin Fab Fragments; Male; Middle Aged; Models, Econometric; Myocardial Revascularization; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Pyridines; Quality-Adjusted Life Years; Recombinant Proteins; Survival Analysis; Tirofiban; Tyrosine; United Kingdom