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.

Platelet, not endothelial, P-selectin is required for neointimal formation after vascular injury.

Background: P-selectin blockade significantly inhibits inflammation and neointimal formation after arterial injury; however, the independent roles of platelet and endothelial P-selectins in this process are unknown. In atherosclerosis, both platelet and endothelial cell P-selectins are important. This study was designed to determine whether P-selectin expression on platelet, endothelial, or both surfaces is critical to the inflammatory response and neointimal formation after arterial injury.

Assessment of hemostatic activation during cardiopulmonary bypass for coronary artery bypass grafting with bivalirudin: results of a pilot study.

Objective: Bivalirudin has been successfully used as a replacement for heparin during on-pump coronary artery bypass grafting. This study was conducted to assess the effects of the currently suggested protocol for bivalirudin on hemostatic activation during cardiopulmonary bypass with and without cardiotomy suction.

Methods: Ten patients scheduled for coronary artery bypass grafting were enrolled.

Prognostic implication of activated partial thromboplastin time after reteplase or half-dose reteplase plus abciximab: results from the GUSTO-V trial.

Aims: To evaluate the relationship between activated partial thromboplastin time (aPTT) and clinical outcomes in the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO-V) trial comparing standard-dose reteplase to half-dose reteplase and abciximab.

Methods And Results: We analysed data on 11,420 patients receiving unfractionated heparin. Peak aPTT levels recorded during the hospitalization were correlated with clinical outcomes.

Effectiveness and safety of bivalirudin during percutaneous coronary intervention in a single medical center.

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.

First experience with direct, selective factor Xa inhibition in patients with non-ST-elevation acute coronary syndromes: results of the XaNADU-ACS Trial.

Background: Unfractionated heparin is widely used in patients with non-ST-elevation acute coronary syndromes but has important limitations. Anticoagulants with predictable kinetics and anticoagulant effects, better efficacy, and greater safety are needed.

Objective: To investigate the efficacy and safety of a direct, selective factor Xa inhibitor, DX-9065a (Daiichi Pharmaceuticals LTD, Inc.

Comparison of ST-segment resolution with combined fibrinolytic and glycoprotein IIb/IIIa inhibitor therapy versus fibrinolytic alone (data from four clinical trials).

We compared combination fibrinolytic plus glycoprotein IIb/IIIa inhibitor therapy with stand-alone fibrinolysis with respect to speed and stability of reperfusion in patients who had acute ST-segment elevation myocardial infarction; data were obtained from 654 patients in 4 trials (Integrilin to Manage Platelet Aggregation to Combat Thrombosis in Acute Myocardial Infarction, Platelet Aggregation Receptor Antagonist Dose Investigation and Reperfusion Gain in Myocardial Infarction, Integrilin and Tenecteplase in Acute Myocardial Infarction, and the Fifth Global Use of Strategies to Open Occluded Coronary Arteries) that compared thrombolytics plus lamifiban, eptifibatide, or abciximab with standard thrombolysis. We found significantly faster and more stable ST-segment recovery with combination therapy starting at 60 minutes (56.7% vs 48.

Bivalirudin versus heparin and glycoprotein IIb/IIIa inhibition among patients with renal impairment undergoing percutaneous coronary intervention (a subanalysis of the REPLACE-2 trial).

Among patients who undergo percutaneous coronary intervention, renal impairment is associated with an excessive risk of bleeding and ischemic events. Bivalirudin provides comparable suppression of ischemic events with a decrease in bleeding events compared with heparin and glycoprotein IIb/IIIa inhibition. We examined the relation between adverse events, renal impairment, and antithrombotic therapy within a randomized comparison.

Impact of female sex on outcome after percutaneous coronary intervention.

Background: Prior reports have suggested that women have increased mortality compared to men following percutaneous coronary intervention (PCI). It remains unclear if this difference is secondary to sex or other confounding variables.

Methods: We sought to examine the characteristics and outcomes of 18039 consecutive women and men undergoing PCI at The Cleveland Clinic Foundation from 1992-2002.

Outcomes of patients with acute coronary syndromes and prior percutaneous coronary intervention: a pooled analysis of three randomized clinical trials.

Aims: We sought to characterize the outcomes of patients with a prior percutaneous coronary intervention (PCI) who presented with a non-ST-segment elevation acute coronary syndrome (ACS).

Methods And Results: We analysed the 30 and 180 day outcomes of 3012 patients with prior PCI and 21 154 patients without prior PCI enrolled in three randomized ACS trials (GUSTO IIb, PURSUIT, and PARAGON-B). The median (25th, 75th percentile) interval between the prior PCI and randomization was 647 (123, 1585) days.

Celecoxib, a selective cyclooxygenase-2 inhibitor, decreases monocyte chemoattractant protein-1 expression and neointimal hyperplasia in the rabbit atherosclerotic balloon injury model.

The inflammation in response to vascular injury is becoming increasingly recognized as a potential contributor to restenosis. Cyclooxygenase-2 (COX-2) is the inducible form of cyclooxygenase and has been shown to be involved in the proinflammatory response of vascular tissue. Bilateral femoral artery lesions were induced by air desiccation in New Zealand White rabbits followed by high cholesterol diet feeding for 28 days.

The effects of niacin on lipoprotein subclass distribution.

Dyslipidemia is a heterogeneous metabolic condition; high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very-low-density lipoprotein represent families of lipoprotein particles that differ in size and composition and vary in atherogenicity. Lipoprotein subclasses containing apolipoprotein B promote atherosclerosis, of which the most atherogenic appear to be the small, dense LDL and large very-low-density lipoprotein subclasses, while the large HDL2 subclass, which transports esterified cholesterol from the periphery to the liver, is considered the more cardioprotective. Niacin has long been known to improve concentrations of all major lipids and lipoproteins, but it also has consistently favorable effects on subclass distribution.

Acute Catheterization and Urgent Intervention Triage strategY (ACUITY) trial: study design and rationale.

Background: Patients with acute coronary syndromes (ACS; unstable angina and non-ST-segment elevation myocardial infarction) are at significant risk for death and myocardial infarction. Early angiography followed by revascularization is considered the treatment of choice for moderate- to high-risk patients with ACS. However, despite the integration of newer therapies including stents, glycoprotein IIb/IIIa inhibitors, and thienopyridines, the rate of adverse ischemic events still remains unacceptably high, and the intensive pharmacologic regimens used to stabilize the disrupted atherosclerotic plaque and support angioplasty and surgical revascularization procedures elicit a high rate of bleeding complications.