Bivalirudin for patients with acute coronary syndromes.

Background: Current guidelines for patients with moderate- or high-risk acute coronary syndromes recommend an early invasive approach with concomitant antithrombotic therapy, including aspirin, clopidogrel, unfractionated or low-molecular-weight heparin, and glycoprotein IIb/IIIa inhibitors. We evaluated the role of thrombin-specific anticoagulation with bivalirudin in such patients.

Methods: We assigned 13,819 patients with acute coronary syndromes to one of three antithrombotic regimens: unfractionated heparin or enoxaparin plus a glycoprotein IIb/IIIa inhibitor, bivalirudin plus a glycoprotein IIb/IIIa inhibitor, or bivalirudin alone.

The influence of peripheral arterial disease on outcomes: a pooled analysis of mortality in eight large randomized percutaneous coronary intervention trials.

Objectives: We aimed to evaluate clinical outcomes among peripheral arterial disease (PAD) patients following percutaneous coronary intervention (PCI).

Background: A significant proportion of patients with coronary artery disease undergoing PCI have concomitant PAD, which may be associated with worse outcomes.

Methods: We performed a pooled analysis of 8 randomized PCI trials.

Use of platelet glycoprotein IIb/IIIa inhibitors in saphenous vein graft percutaneous coronary intervention and clinical outcomes.

Platelet glycoprotein (GP) IIb/IIIa inhibitors are widely used in percutaneous coronary intervention (PCI). Previous studies have suggested that they do not offer benefit in saphenous vein graft PCI. Nonetheless, their use remains widespread during vein graft angioplasty.

Stent-assisted detachable coil embolization of pseudoaneurysms in the coronary circulation.

Pseudoaneurysms in the coronary circulation are an uncommon occurrence that can develop spontaneously in the setting of atherosclerosis or can develop after catheter-based coronary interventions. The natural history, clinical outcome, and optimal therapy for pseudoaneurysms in the coronary circulation are not clearly established. Recent advances in the techniques and technologies used for endovascular treatment of intracranial aneurysms may be applicable to the management of coronary aneurysms and pseudoaneurysms.

Direct thrombin inhibition appears to be a safe and effective anticoagulant for percutaneous bypass graft interventions.

Background: Percutaneous coronary interventions (PCI) of coronary artery bypass grafts (CABG) are associated with worse outcomes compared with those of native coronary PCI. Little is known concerning the use of direct thrombin inhibition during CABG intervention. The objective of this report is to examine the safety and efficacy of bivalirudin with GPIIb/IIIa blockade inhibition in patients undergoing CABG PCI.

Provisional glycoprotein IIb/IIIa blockade in a randomized investigation of bivalirudin versus heparin plus planned glycoprotein IIb/IIIa inhibition during percutaneous coronary intervention: predictors and outcome in the Randomized Evaluation in Percutaneous coronary intervention Linking Angiomax to Reduced Clinical Events (REPLACE)-2 trial.

Background: The REPLACE-2 trial demonstrated the noninferiority of bivalirudin with provisional glycoprotein IIb/IIIa (GPIIb/IIIa) blockade as compared with heparin plus planned GPIIb/IIIa blockade among patients undergoing percutaneous coronary revascularization. Provisional drug was used in 374 (6%) of the 6010 patients. We sought to analyze the predictors for provisional drug use and to assess the outcomes in this cohort.

Outcomes of patients with acute coronary syndromes who are treated with bivalirudin during percutaneous coronary intervention: an analysis from the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE-2) trial.

Background: The REPLACE-2 trial demonstrated that bivalirudin with provisional glycoprotein IIb/IIIa (GPIIb/IIIa) inhibition is not inferior to heparin plus GPIIb/IIIa inhibition in patients undergoing percutaneous coronary intervention. The extent to which this applies to patients with acute coronary syndromes (ACS) is unclear. Therefore, we sought to determine if bivalirudin has similar efficacy in ACS patients as compared with "stable" patients in the REPLACE-2 trial.

Use of ticlopidine and cilostazol after intracoronary drug-eluting stent placement in a patient with previous clopidogrel-induced thrombotic thrombocytopenic purpura: a case report.

Thrombotic thrombocytopenic purpura (TTP) is an extremely rare but potentially fatal adverse reaction to the thienopyridines, clopidogrel and ticlopidine. We report the case of a patient with a history of clopidogrel-induced TTP who subsequently was successfully treated with aspirin, ticlopidine and cilostazol after stenting for severe, symptomatic coronary artery disease. This case supports the theory that clopidogrel and ticlopidine mediate TTP through slightly different mechanisms and that ticlopidine may be safely used in this setting if absolutely necessary.

Planned versus provisional use of glycoprotein IIb/IIIa inhibitors in smokers undergoing percutaneous coronary intervention.

Postmortem and angiographic studies have demonstrated that thrombosis is the primary cause of coronary artery occlusion in smokers. Further, smokers have high levels of fibrinogen, increased platelet aggregation, and more platelet-dependent thrombin generation than do nonsmokers, suggesting that glycoprotein (GP) IIb/IIIa inhibitor use during percutaneous coronary intervention (PCI) may be especially useful among smokers. We evaluated a subpopulation of active smokers in the REPLACE-2 trial to assess the effect of treating smokers with bivalirudin and provisional GP IIb/IIIa blockade compared with heparin and planned GP IIb/IIIa blockade.

Angiographic adverse events, creatine kinase-MB elevation, and ischemic end points complicating percutaneous coronary intervention (a REPLACE-2 substudy).

Several angiographic adverse events during coronary balloon angioplasty have been associated with increased creatine kinase-MB (CK-MB) enzymes and adverse clinical outcomes. The significance of angiographic adverse events in the stent era has not been widely studied. We analyzed 10 types of angiographic adverse events that were reported in the 6,010-patient Second Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE-2) trial to determine their relation to CK-MB elevation and clinical ischemic end points after percutaneous coronary intervention (PCI).

Ischemic and bleeding outcomes in women treated with bivalirudin during percutaneous coronary intervention: a subgroup analysis of the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 trial.

Background: Outcomes in women undergoing percutaneous coronary intervention (PCI) in the contemporary era are poorly defined. The REPLACE-2 trial demonstrated that bivalirudin with provisional glycoprotein IIb/IIIa (GpIIb-IIIa) blockade is noninferior to heparin with planned GpIIb-IIIa blockade during PCI, with regard to ischemic and bleeding end points.

Objectives: The aim of this study was to define sex-based clinical ischemic and bleeding outcomes from the REPLACE-2 trial.

Optimizing use of revascularization and clinical outcomes in ST-elevation myocardial infarction: insights from the GUSTO-V trial.

Aims: To examine the relationship between revascularization within 7 days and 1-year mortality among ST-elevation myocardial infarction patients enrolled in GUSTO-V trial (n=13 451). To examine the relative contribution of system and patient level factors to the variation in international revascularization rates, and their impact on mortality outcomes.

Methods And Results: Patients from North America (USA, Canada), Australia, and Europe (UK, France, Germany, Italy, Spain, Poland, Norway, The Netherlands, Belgium, Finland) were included in the study.

Anticoagulation with bivalirudin for off-pump coronary artery bypass grafting: the results of the EVOLUTION-OFF study.

Objectives: 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.

A comparison of bivalirudin to heparin with protamine reversal in patients undergoing cardiac surgery with cardiopulmonary bypass: the EVOLUTION-ON study.

Objectives: 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.

Methods: We conducted a randomized, open-label, multicenter trial comparing heparin with protamine reversal to bivalirudin in patients undergoing cardiac surgery with cardiopulmonary bypass.

A comparison of the clinical impact of bleeding measured by two different classifications among patients with acute coronary syndromes.

Objectives: The goal of this study was to determine the association between Thrombolysis In Myocardial Infarction (TIMI) and Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) bleeding and clinical outcomes.

Background: There are limited data on the relative utility of either scale at predicting clinical outcomes in patients with non-ST-segment elevation acute coronary syndromes (ACS).

Methods: Pooled data from two randomized trials of patients with ACS (n = 15,454) were analyzed to determine the association between TIMI and GUSTO bleeding and 30-day and 6-month death/myocardial infarction (MI) using Cox proportional hazards modeling that included bleeding as a time-dependent covariate.

Clinical end point definitions after percutaneous coronary intervention and their relationship to late mortality: an assessment by attributable risk.

Objectives: To explore the relative and absolute risks associated with various definitions for myocardial infarction, bleeding and revascularisation within the context of percutaneous coronary intervention (PCI).

Methods: The REPLACE-2 (randomised evaluation of PCI linking Angiomax to reduced clinical events) database of patients undergoing PCI was used. Various definitions of myocardial infarction, bleeding and revascularisation were modelled by logistic regression assessing their relationship with 12-month mortality.

Bivalirudin vs heparin in percutaneous coronary intervention: a pooled analysis.

Objective: This study evaluates outcomes with bivalirudin vs heparin in various patient subgroups and the overall population during percutaneous coronary interventions (PCI).

Background: Recent data suggest that bivalirudin, a reversible direct thrombin inhibitor, provides ischemic protection superior to heparin and comparable to heparin plus glycoprotein (GP) IIb/IIIa inhibitors but with significantly fewer bleeding complications. Whether this advantage persists in different subgroups has not been fully defined.

Peroxisome proliferator-activated receptor gamma down-regulates receptor for advanced glycation end products and inhibits smooth muscle cell proliferation in a diabetic and nondiabetic rat carotid artery injury model.

Diabetes is associated with an increase in circulating advanced glycosylation end products (AGEs) and the increased expression of the receptor for AGEs (RAGE). Inhibition of AGE/RAGE binding through the administration of soluble RAGE (sRAGE) has been shown to decrease neointimal hyperplasia. Peroxisome proliferator-activated receptor gamma (PPARgamma), which inhibits neointimal hyperplasia, has been shown to decrease RAGE expression in cultured endothelial cells.

Utilization of catheterization and revascularization procedures in patients with non-ST segment elevation acute coronary syndrome over the last decade.

The degree to which catheterization and revascularization procedures are utilized in patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS) during hospitalization has broad implications with respect to initial pharmacotherapeutic decisions (upfront therapies), treatment and hospital transfer protocols, guideline recommendations, and allocation of training, material, and financial resources. Analysis of data from multiple trials and registries of patients with NSTE-ACS has the potential to assess more broadly utilization of invasive and revascularization procedures and provide a wide angle or bird's-eye view of the management of such patients, complementing the data obtained from any one trial or registry. We therefore undertook a systematic overview of all large trials and registries of patients with NSTE-ACS conducted over the last decade that were deemed appropriate to provide information on catheterization and revascularization procedures.

The relationship between baseline risk and mortality in ST-elevation acute myocardial infarction treated with pharmacological reperfusion: insights from the Global Utilization of Strategies To open Occluded arteries (GUSTO) V trial.

Background: We studied the potential interaction between baseline risk of death and treatment with either standard fibrinolytic monotherapy or combination fibrin and platelet lysis with respect to outcome of patients with ST-elevation myocardial infarction (STEMI) enrolled in the Global Utilization of Strategies To open Occluded arteries (GUSTO) V trial.

Methods: Using the Thrombolysis in Myocardial Infarction (TIMI) risk score (0-14 points) for STEMI, we analyzed the 30-day and 1-year mortality according to treatment assignment and risk category. Multivariable analysis was performed to identify the potential interactions between treatment and baseline risk.

Direct thrombin inhibitors.

Direct thrombin inhibitors (DTIs) are a new class of therapeutics possessing theoretic advantages over unfractionated heparin (UFH). In contrast to UFH, DTIs do not activate platelets, have no circulating inhibitors, and bind to both free and clot-bound thrombin. These theoretical advantages have spurred clinical trials investigating DTIs in a variety of cardiovascular indications.

Use of bivalirudin during percutaneous coronary intervention in patients with diabetes mellitus: an analysis from the randomized evaluation in percutaneous coronary intervention linking angiomax to reduced clinical events (REPLACE)-2 trial.

Objectives: The objective of this study was to confirm that the efficacy and safety of percutaneous coronary intervention (PCI) in diabetic patients are not compromised by a bivalirudin-based antithrombotic strategy.

Background: Previous studies have shown a survival benefit with use of platelet glycoprotein (GP) IIb/IIIa inhibitors in diabetic patients undergoing PCI. The Randomized Evaluation in Percutaneous Coronary Intervention Linking Angiomax to Reduced Clinical Events (REPLACE)-2 trial showed the non-inferiority of a strategy of bivalirudin with provisional GP IIb/IIIa inhibition compared with routine GP IIb/IIIa inhibition.

Characterization of myocardial infarction as an end point in two large trials of acute coronary syndromes.

Myocardial infarction (MI) is a key component of composite end points in trials that evaluate new therapies in non-ST-segment elevation acute coronary syndromes. Types of MI events in these trials have not been well characterized. A similar clinical-events classification process adjudicated all suspected MI end points in the PURSUIT and PARAGON B trials.