Rationale and design of the Patient Related OuTcomes with Endeavor versus Cypher stenting Trial (PROTECT): randomized controlled trial comparing the incidence of stent thrombosis and clinical events after sirolimus or zotarolimus drug-eluting stent implantation.

Drug-eluting stents (DES) reduce restenosis rates compared to bare-metal stents. Most trials using DES enrolled selected patient and lesion subtypes, and primary endpoint focused on angiographic metrics or relatively short-term outcomes. When DES are used in broader types of lesions and patients, important differences may emerge in long-term outcomes between stent types, particularly the incidence of late stent thrombosis.

Smoking, clopidogrel, and mortality in patients with established cardiovascular disease.

Background: Smoking increases platelet aggregability and the degree of platelet inhibition by clopidogrel on ex vivo platelet function tests. Whether smoking status affects the relationship between clopidogrel and clinical outcomes is unknown.

Methods And Results: We evaluated the relationship between smoking status (current smoker, former smoker, or never-smoker) and treatment with clopidogrel on the risk of all-cause, cardiovascular, and cancer mortality among the 12 152 participants from the CHARISMA (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance) trial who had established cardiovascular disease.

Cardiovascular event rates in patients with cerebrovascular disease and atherothrombosis at other vascular locations: results from 1-year outcomes in the Japanese REACH Registry.

The REduction of Atherothrombosis for Continued Health (REACH) Registry is a large, international, prospective cohort of patients with atherothrombosis or multiple (>or=3) risk factors (MRFs) for atherothrombosis. Japanese patients (n=5193) were enrolled into the REACH registry between August and December 2004. One-year event rate in patients with cerebrovascular disease (CVD) was compared with that of patients with symptomatic atherothrombosis at other locations.

Regional and practice variation in adherence to guideline recommendations for secondary and primary prevention among outpatients with atherothrombosis or risk factors in the United States: a report from the REACH Registry.

Background: To reduce atherothrombosis-related morbidity and mortality, implementation of guideline-recommended therapies for primary and secondary prevention is necessary. Few data are available for outpatients in actual clinical practice, especially those without known heart disease treated by physicians trained in different specialties across the geographic regions of the United States.

Methods: The REduction of Atherothrombosis for Continued Health (REACH) Registry compiled data on atherosclerosis risk factors and treatment in an office-based setting.

Drug treatment and cost of cardiovascular disease in Australia.

Australia's Pharmaceutical Benefits Scheme supports the use of effective drugs for the prevention and control of cardiovascular risk factors. However, there are little data available describing per person costs of medication in primary prevention and secondary prevention in the community. We aim to understand annual expenditure on cardiovascular medicines according to the level and extent of cardiovascular disease, using participants enrolled in the Reduction of Atherothrombosis for Continued Health (REACH) registry.

The efficacy and safety of prasugrel with and without a glycoprotein IIb/IIIa inhibitor in patients with acute coronary syndromes undergoing percutaneous intervention: a TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis In Myocardial Infarction 38) analysis.

Objectives: We evaluated the efficacy and safety of prasugrel and clopidogrel in the setting of a glycoprotein (GP) IIb/IIIa inhibitor.

Background: Prasugrel reduced cardiovascular events as compared with clopidogrel in TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction 38) but with increased bleeding.

Methods: Researchers in the TRITON-TIMI 38 randomized 13,608 subjects with acute coronary syndrome undergoing percutaneous coronary intervention to prasugrel versus clopidogrel.

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.

Retinal microvascularisation abnormalities and cardiovascular risk.

The progress of retinal imaging techniques has made retinal microvascular circulation easier to study. A number of observational studies were conducted to characterise the different abnormalities encountered and to determine the factors contributing to their onset. Three lesion groups were highlighted, including reduced arteriolar diameter, venular dilatation and retinopathy lesions.

Validity of a risk-prediction tool for hospital mortality: the Global Registry of Acute Coronary Events.

Background: The Global Registry of Acute Coronary Events (GRACE) risk model provides a simple method for determining the probability of hospital death in acute coronary syndrome (ACS). The aim of this study was to explore the impact of modeling techniques on the risk model when generating predictions.

Methods: Patients with ACS (n = 48,023) with or without ST-segment elevation myocardial infarction (STEMI) were enrolled (123 hospitals, 14 countries) between April 1999 and June 2006.

Clinical outcomes of patients with diabetic nephropathy randomized to clopidogrel plus aspirin versus aspirin alone (a post hoc analysis of the clopidogrel for high atherothrombotic risk and ischemic stabilization, management, and avoidance [CHARISMA] trial).

No prospective randomized trial has specifically examined the long-term outcomes of clopidogrel use in patients with chronic kidney disease. This study aimed to determine the risks and benefits of long-term clopidogrel administration in patients with diabetic nephropathy, the most common form of chronic kidney disease. We performed a post hoc analysis of the CHARISMA trial, which randomly assigned patients without active acute coronary syndrome, but with established atherosclerotic disease (symptomatic) or multiple risk factors for atherosclerotic disease (asymptomatic), to clopidogrel plus aspirin versus placebo plus aspirin.

Cardiovascular ischemic event rates in outpatients with symptomatic atherothrombosis or risk factors in the united states: insights from the REACH Registry.

Background: Atherothrombosis, defined as coronary artery, cerebrovascular, and peripheral arterial disease, is the leading cause of death in the United States. Limited data are available from outpatient populations to describe contemporary cardiovascular ischemic event rates and associated use of risk reduction treatments in patients with clinically manifest, or at risk for, atherothrombosis. The REduction of Atherothrombosis for Continued Health (REACH) Registry is an international, prospective, observational study of patients with either documented atherothrombotic syndromes or 3 or more risk factors designed to fill this knowledge gap.

Fondaparinux versus Enoxaparin in non-ST-elevation acute coronary syndromes: short-term cost and long-term cost-effectiveness using data from the Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators (OASIS-5) trial.

Background: The study aimed to compare the short-term costs and long-term cost-effectiveness of 2 antithrombotics, fondaparinux and enoxaparin, for non-ST-elevation acute coronary syndrome in the United States.

Methods: It was based on a large randomized trial of 20,078 patients Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators [OASIS-5] comparing the therapies in these patients. In OASIS-5, fondaparinux patients had about half the rate of major bleeding 9 days after randomization and at least as good clinical outcomes (death, myocardial infarction, major bleeding and stroke) after 6 months of follow-up.

Lowering mortality in ST-elevation myocardial infarction and non-ST-elevation myocardial infarction: key prehospital and emergency room treatment strategies.

Achieving optimal outcomes in patients with acute coronary syndromes depends on early reperfusion supported by rapid initiation of adjunctive antiplatelet and anticoagulant therapy. The use of the ambulance setting to initiate treatment provides an opportunity to dramatically reduce the time between symptom onset and reperfusion, and a growing body of evidence shows that prehospital reperfusion therapy is associated with significantly better short-term and long-term outcomes than in-hospital administration of the same treatment. In patients with ST-segment elevation myocardial infarction, fibrinolysis must be supported by optimal antiplatelet therapy.

Association of elevated fasting glucose with increased short-term and 6-month mortality in ST-segment elevation and non-ST-segment elevation acute coronary syndromes: the Global Registry of Acute Coronary Events.

Background: Elevated blood glucose level at admission is associated with worse outcome after a myocardial infarction. The impact of elevated glucose level, particularly fasting glucose, is less certain in non-ST-segment elevation acute coronary syndromes. We studied the relationship between elevated fasting blood glucose levels and outcome across the spectrum of ST-segment elevation and non-ST-segment elevation acute coronary syndromes in a large multicenter population broadly representative of clinical practice.

Patients with peripheral arterial disease in the CHARISMA trial.

Aims: The aim of this study was to determine whether clopidogrel plus aspirin provides greater protection against major cardiovascular events than aspirin alone in patients with peripheral arterial disease (PAD).

Methods And Results: This is a post hoc analysis of the 3096 patients with symptomatic (2838) or asymptomatic (258) PAD from the CHARISMA trial. The rate of cardiovascular death, myocardial infarction (MI), or stroke (primary endpoint) was higher in patients with PAD than in those without PAD: 8.

Genetic determinants of response to clopidogrel and cardiovascular events.

Background: Pharmacogenetic determinants of the response of patients to clopidogrel contribute to variability in the biologic antiplatelet activity of the drug. The effect of these determinants on clinical outcomes after an acute myocardial infarction is unknown.

Methods: We consecutively enrolled 2208 patients presenting with an acute myocardial infarction in a nationwide French registry and receiving clopidogrel therapy.

Prevalence, clinical profile, and cardiovascular outcomes of atrial fibrillation patients with atherothrombosis.

Background: Atrial fibrillation (AF) is a major risk factor (RF) for ischemic stroke. Its prevalence and prognostic impact in patients with atherothrombosis are unclear.

Methods: Risk factors, drug usage, and 1-year cardiovascular (CV) outcomes (CV death, myocardial infarction [MI], and stroke) were compared in AF and non-AF patients from the REduction of Atherothrombosis for Continued Health (REACH) Registry, an international, prospective cohort of 68,236 stable outpatients with established atherothrombosis or>or=3 atherothrombotic RFs.

Cardiovascular risk factor control and outcomes in peripheral artery disease patients in the Reduction of Atherothrombosis for Continued Health (REACH) Registry.

Objectives: To examine differences in risk factor (RF) management between peripheral artery disease (PAD) and coronary artery (CAD) or cerebrovascular disease (CVD), as well as the impact of RF control on major 1-year cardiovascular (CV) event rates.

Methods: The REACH Registry recruited >68000 outpatients aged >or=45 years with established atherothrombotic disease or >or=3 RFs for atherothrombosis. The predictors of RF control that were evaluated included: (1) patient demographics, (2) mode of PAD diagnosis, and (3) concomitant CAD and/or CVD.

The Essen stroke risk score predicts recurrent cardiovascular events: a validation within the REduction of Atherothrombosis for Continued Health (REACH) registry.

Background And Purpose: Predictive scores are important tools for stratifying patients based on the risk of future (cerebro)vascular events and for selecting potential prevention therapy. Recently, the Essen Stroke Risk Score (ESRS) was derived from cerebrovascular patients in the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial. We aimed to validate the ESRS in a large cohort of outpatients with previous transient ischemic attack or stroke from the REduction of Atherothrombosis for Continued Health (REACH) Registry.

Antithrombotic therapy with fondaparinux in relation to interventional management strategy in patients with ST- and non-ST-segment elevation acute coronary syndromes: an individual patient-level combined analysis of the Fifth and Sixth Organization to Assess Strategies in Ischemic Syndromes (OASIS 5 and 6) randomized trials.

Background: The Fifth and Sixth Organization to Assess Strategies in Ischemic Syndromes (OASIS 5 and 6) trials evaluated fondaparinux, a synthetic factor Xa inhibitor, in patients with non-ST- and ST-segment elevation acute coronary syndromes, respectively. Combined results for these 2 trials on major efficacy and safety outcomes and data on the effects of fondaparinux in relation to interventional management strategy have not been previously reported.

Methods And Results: We performed an individual patient-level combined analysis of 26 512 patients from the OASIS 5 and 6 trials who were randomized in a double-blind fashion to fondaparinux 2.