Methylprednisolone in patients undergoing cardiopulmonary bypass (SIRS): a randomised, double-blind, placebo-controlled trial.

Background: Cardiopulmonary bypass initiates a systemic inflammatory response syndrome that is associated with postoperative morbidity and mortality. Steroids suppress inflammatory responses and might improve outcomes in patients at high risk of morbidity and mortality undergoing cardiopulmonary bypass. We aimed to assess the effects of steroids in patients at high risk of morbidity and mortality undergoing cardiopulmonary bypass.

Extracranial Systemic Embolic Events in Patients With Nonvalvular Atrial Fibrillation: Incidence, Risk Factors, and Outcomes.

Background: Nonvalvular atrial fibrillation is a major cause of thromboembolic events. In comparison with atrial fibrillation-related stroke, extracranial systemic embolic events (SEEs) remain poorly defined.

Methods And Results: All suspected SEEs reported among 37 973 participants of 4 large contemporary randomized clinical trials of anticoagulation in atrial fibrillation were independently readjudicated for clinical and objective evidence of sudden loss of perfusion of a limb or organ.

Cardioverter defibrillator implantation without induction of ventricular fibrillation: a single-blind, non-inferiority, randomised controlled trial (SIMPLE).

Background: Defibrillation testing by induction and termination of ventricular fibrillation is widely done at the time of implantation of implantable cardioverter defibrillators (ICDs). We aimed to compare the efficacy and safety of ICD implantation without defibrillation testing versus the standard of ICD implantation with defibrillation testing.

Methods: In this single-blind, randomised, multicentre, non-inferiority trial (Shockless IMPLant Evaluation [SIMPLE]), we recruited patients aged older than 18 years receiving their first ICD for standard indications at 85 hospitals in 18 countries worldwide.

Aspirin in patients undergoing noncardiac surgery.

Background: There is substantial variability in the perioperative administration of aspirin in patients undergoing noncardiac surgery, both among patients who are already on an aspirin regimen and among those who are not.

Methods: Using a 2-by-2 factorial trial design, we randomly assigned 10,010 patients who were preparing to undergo noncardiac surgery and were at risk for vascular complications to receive aspirin or placebo and clonidine or placebo. The results of the aspirin trial are reported here.

Clonidine in patients undergoing noncardiac surgery.

Background: Marked activation of the sympathetic nervous system occurs during and after noncardiac surgery. Low-dose clonidine, which blunts central sympathetic outflow, may prevent perioperative myocardial infarction and death without inducing hemodynamic instability.

Methods: We performed a blinded, randomized trial with a 2-by-2 factorial design to allow separate evaluation of low-dose clonidine versus placebo and low-dose aspirin versus placebo in patients with, or at risk for, atherosclerotic disease who were undergoing noncardiac surgery.

Effects of off-pump and on-pump coronary-artery bypass grafting at 1 year.

Background: Previously, we reported that there was no significant difference at 30 days in the rate of a primary composite outcome of death, myocardial infarction, stroke, or new renal failure requiring dialysis between patients who underwent coronary-artery bypass grafting (CABG) performed with a beating-heart technique (off-pump) and those who underwent CABG performed with cardiopulmonary bypass (on-pump). We now report results on quality of life and cognitive function and on clinical outcomes at 1 year.

Methods: We enrolled 4752 patients with coronary artery disease who were scheduled to undergo CABG and randomly assigned them to undergo the procedure off-pump or on-pump.

Off-pump or on-pump coronary-artery bypass grafting at 30 days.

Background: The relative benefits and risks of performing coronary-artery bypass grafting (CABG) with a beating-heart technique (off-pump CABG), as compared with cardiopulmonary bypass (on-pump CABG), are not clearly established.

Methods: At 79 centers in 19 countries, we randomly assigned 4752 patients in whom CABG was planned to undergo the procedure off-pump or on-pump. The first coprimary outcome was a composite of death, nonfatal stroke, nonfatal myocardial infarction, or new renal failure requiring dialysis at 30 days after randomization.

Rationale and design of the coronary artery bypass grafting surgery off or on pump revascularization study: a large international randomized trial in cardiac surgery.

Background: Uncertainty remains regarding the benefits and risks of the technique of operating on a beating heart (off pump) for coronary artery bypass grafting (CABG) surgery versus on-pump CABG. Prior trials had few events and relatively short follow-up. There is a need for a large randomized, controlled trial with long-term follow-up to inform both the short- and long-term impact of the 2 approaches to CABG.

Dronedarone in high-risk permanent atrial fibrillation.

Background: Dronedarone restores sinus rhythm and reduces hospitalization or death in intermittent atrial fibrillation. It also lowers heart rate and blood pressure and has antiadrenergic and potential ventricular antiarrhythmic effects. We hypothesized that dronedarone would reduce major vascular events in high-risk permanent atrial fibrillation.

The cost of clopidogrel use in atrial fibrillation in the ACTIVE-A trial.

Background: The Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events-Aspirin (ACTIVE-A) demonstrated that in patients with atrial fibrillation unsuitable for vitamin K antagonist (VKA) therapy, a combination of clopidogrel and aspirin reduced stroke risk by 28% but increased major hemorrhage risk by 57%. This analysis examined cost implications of adding clopidogrel to aspirin (C+A) for ACTIVE-A patients.

Methods: Health care use was extracted for each patient.

Radial versus femoral access for coronary angiography and intervention in patients with acute coronary syndromes (RIVAL): a randomised, parallel group, multicentre trial.

Background: Small trials have suggested that radial access for percutaneous coronary intervention (PCI) reduces vascular complications and bleeding compared with femoral access. We aimed to assess whether radial access was superior to femoral access in patients with acute coronary syndromes (ACS) who were undergoing coronary angiography with possible intervention.

Methods: The RadIal Vs femorAL access for coronary intervention (RIVAL) trial was a randomised, parallel group, multicentre trial.

Irbesartan in patients with atrial fibrillation.

Background: The risk of cardiovascular events among patients with atrial fibrillation is high. We evaluated whether irbesartan, an angiotensin-receptor blocker, would reduce this risk.

Methods: We randomly assigned patients with a history of risk factors for stroke and a systolic blood pressure of at least 110 mm Hg to receive either irbesartan at a target dose of 300 mg once daily or double-blind placebo.

Design and rationale of the radial versus femoral access for coronary intervention (RIVAL) trial: a randomized comparison of radial versus femoral access for coronary angiography or intervention in patients with acute coronary syndromes.

Background: Major bleeding in acute coronary syndromes (ACS) is associated with an increased risk of subsequent mortality and recurrent ischemic events. Observational data and small randomized trials suggest that radial instead of femoral access for coronary angiography/intervention results in fewer bleeding complications, with preserved and possibly improved efficacy. Radial access versus femoral access has yet to be formally evaluated in a randomized trial adequately powered for the comparison of clinically important outcomes.

Efficacy and safety of fondaparinux in patients with ST-segment elevation myocardial infarction across the age spectrum. Results from the Organization for the Assessment of Strategies for Ischemic Syndromes 6 (OASIS-6) trial.

Aims: The OASIS-6 trial demonstrated the benefit of fondaparinux in patients with ST-segment elevation myocardial infarction (STEMI) not undergoing primary percutaneous coronary intervention. Elderly compared to younger patients are at higher risk of bleeding and could have a different balance of benefits and risks when treated with antithrombotic therapy.

Methods And Results: We explored the efficacy and safety of fondaparinux compared to control according to age tertiles in 12,092 patients with STEMI in the OASIS-6 trial.

Fondaparinux with UnfracTionated heparin dUring Revascularization in Acute coronary syndromes (FUTURA/OASIS 8): a randomized trial of intravenous unfractionated heparin during percutaneous coronary intervention in patients with non-ST-segment elevation acute coronary syndromes initially treated with fondaparinux.

Background: There is uncertainty regarding the optimal adjunctive unfractionated heparin (UFH) regimen for percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) treated with fondaparinux.

Objective: The aim of this study is to evaluate the safety of 2 dose regimens of adjunctive intravenous UFH during PCI in high-risk patients with NSTE-ACS initially treated with fondaparinux and referred for early coronary angiography.

Design: This is an international prospective cohort study of approximately 4,000 high-risk patients presenting to hospital with unstable angina or non-ST-segment elevation myocardial infarction, treated with fondaparinux as initial medical therapy, and referred for early coronary angiography with a view to revascularization.

Dose comparisons of clopidogrel and aspirin in acute coronary syndromes.

Background: Clopidogrel and aspirin are widely used for patients with acute coronary syndromes and those undergoing percutaneous coronary intervention (PCI). However, evidence-based guidelines for dosing have not been established for either agent.

Methods: We randomly assigned, in a 2-by-2 factorial design, 25,086 patients with an acute coronary syndrome who were referred for an invasive strategy to either double-dose clopidogrel (a 600-mg loading dose on day 1, followed by 150 mg daily for 6 days and 75 mg daily thereafter) or standard-dose clopidogrel (a 300-mg loading dose and 75 mg daily thereafter) and either higher-dose aspirin (300 to 325 mg daily) or lower-dose aspirin (75 to 100 mg daily).

Double-dose versus standard-dose clopidogrel and high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT-OASIS 7): a randomised factorial trial.

Background: Clopidogrel and aspirin are the most commonly used antiplatelet therapies for percutaneous coronary intervention (PCI). We assessed the effect of various clopidogrel and aspirin regimens in prevention of major cardiovascular events and stent thrombosis in patients undergoing PCI.

Methods: The CURRENT-OASIS 7 trial was undertaken in 597 centres in 39 countries.

Low-dose vs standard-dose unfractionated heparin for percutaneous coronary intervention in acute coronary syndromes treated with fondaparinux: the FUTURA/OASIS-8 randomized trial.

Context: The optimal unfractionated heparin regimen for percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation acute coronary syndromes treated with fondaparinux is uncertain.

Objective: To compare the safety of 2 unfractionated heparin regimens during PCI in high-risk patients with non-ST-segment elevation acute coronary syndromes initially treated with fondaparinux.

Design, Setting, And Participants: Double-blind randomized parallel-group trial in 179 hospitals in 18 countries involving 2026 patients undergoing PCI within 72 hours, nested within a cohort of 3235 high-risk patients with non-ST-segment elevation acute coronary syndromes initially treated with fondaparinux enrolled from February 2009 to March 2010.

Mortality predictors and effects of antithrombotic therapies in atrial fibrillation: insights from ACTIVE-W.

Aims: To assess the risk of death after the occurrence of different types of non-fatal events in patients with atrial fibrillation (AF). Antithrombotic therapies in AF have primarily focused on stroke prevention and bleeding. However, strokes and bleeds differ in severity, and the level of severity may differently impact mortality.

Relationship between baseline haemoglobin and major bleeding complications in acute coronary syndromes.

Aims: In patients with acute coronary syndromes (ACS), the negative impact of baseline haemoglobin levels on ischaemic events, particularly death, is well established, but the association with bleeding risk is less well studied. The aim of this study was to assess the impact of baseline haemoglobin levels on major bleeding complications.

Methods And Results: Pooled analysis of OASIS 5 and 6 data involving 32 170 patients with ACS with and without ST-segment elevation was performed.

Efficacy and safety of fondaparinux versus enoxaparin in patients with acute coronary syndromes treated with glycoprotein IIb/IIIa inhibitors or thienopyridines: results from the OASIS 5 (Fifth Organization to Assess Strategies in Ischemic Syndromes) trial.

Objectives: This study sought to evaluate the relative safety and efficacy of fondaparinux and enoxaparin in patients with acute coronary syndromes (ACS) treated with glycoprotein (GP) IIb/IIIa inhibitors or thienopyridines.

Background: The OASIS 5 (Fifth Organization to Assess Strategies in Ischemic Syndromes) trial showed that fondaparinux reduced major bleeding by 50% compared with enoxaparin while preserving similar efficacy. Whether this benefit is consistent in the presence or absence of concurrent antiplatelet therapy with clopidogrel and GP IIb/IIIa inhibitors is unknown.

Early versus delayed invasive intervention in acute coronary syndromes.

Background: Earlier trials have shown that a routine invasive strategy improves outcomes in patients with acute coronary syndromes without ST-segment elevation. However, the optimal timing of such intervention remains uncertain.

Methods: We randomly assigned 3031 patients with acute coronary syndromes to undergo either routine early intervention (coronary angiography < or = 24 hours after randomization) or delayed intervention (coronary angiography > or = 36 hours after randomization).

Effect of clopidogrel added to aspirin in patients with atrial fibrillation.

Background: Vitamin K antagonists reduce the risk of stroke in patients with atrial fibrillation but are considered unsuitable in many patients, who usually receive aspirin instead. We investigated the hypothesis that the addition of clopidogrel to aspirin would reduce the risk of vascular events in patients with atrial fibrillation.

Methods: A total of 7554 patients with atrial fibrillation who had an increased risk of stroke and for whom vitamin K-antagonist therapy was unsuitable were randomly assigned to receive clopidogrel (75 mg) or placebo, once daily, in addition to aspirin.

Fondaparinux compared to enoxaparin in patients with acute coronary syndromes without ST-segment elevation: outcomes and treatment effect across different levels of risk.

Background: The OASIS-5 (Organization to Assess Strategies in Ischemic Syndromes-5) trial demonstrated that fondaparinux was noninferior to enoxaparin while reducing the risk of bleeding by 50%. The objectives of our study were to assess the effects of fondaparinux compared to enoxaparin in patients stratified by their Global Registry of Acute Coronary Events (GRACE) score and to examine the ability of the GRACE score to predict bleeding in patients with acute coronary syndromes (ACS).

Methods: We analyzed efficacy and safety according to the GRACE admission risk score.

Early invasive compared with a selective invasive strategy in women with non-ST-elevation acute coronary syndromes: a substudy of the OASIS 5 trial and a meta-analysis of previous randomized trials.

Aims: The aim of this study was to compare benefits and risks of a routine invasive compared with a selective invasive strategy in women with non-ST-elevation acute coronary syndromes.

Methods And Results: We randomly assigned 184 women, either to a routine or to a selective invasive strategy as a substudy to the OASIS 5 trial, who were followed for 2 years. Meta-analysis of data from previous randomized trials was also done.