Apixaban compared to heparin/vitamin K antagonist in patients with atrial fibrillation scheduled for cardioversion: the EMANATE trial.

Aim: The primary objective was to compare apixaban to heparin/vitamin K antagonist (VKA) in patients with atrial fibrillation (AF) and ≤48 h anticoagulation prior to randomization undergoing cardioversion.

Methods: One thousand five hundred patients were randomized. The apixaban dose of 5 mg b.

A 3-year study of atorvastatin in children and adolescents with heterozygous familial hypercholesterolemia.

Background: The efficacy and safety of atorvastatin in children/adolescents aged 10-17 years with heterozygous familial hypercholesterolemia (HeFH) have been demonstrated in trials of up to 1 year in duration. However, the efficacy/safety of >1 year use of atorvastatin in children/adolescents with HeFH, including children from 6 years of age, has not been assessed.

Objective: To characterize the efficacy and safety of atorvastatin over 3 years and to assess the impact on growth and development in children aged 6-15 years with HeFH.

Apixaban compared with parenteral heparin and/or vitamin K antagonist in patients with nonvalvular atrial fibrillation undergoing cardioversion: Rationale and design of the EMANATE trial.

Background: Stroke prevention in anticoagulation-naïve patients with atrial fibrillation undergoing cardioversion has not been systematically studied.

Objective: To determine outcomes in anticoagulation-naïve patients (defined as those receiving an anticoagulant for <48 hours during the index episode of atrial fibrillation) scheduled for cardioversion.

Methods: This is a randomized, prospective, open-label, real-world study comparing apixaban to heparin plus warfarin.

Differing predictive relationships between baseline LDL-C, systolic blood pressure, and cardiovascular outcomes.

Background: Traditional cardiovascular risk factors, such as hypertension and dyslipidemia, predispose individuals to cardiovascular disease, particularly patients with diabetes. We investigated the predictive value of baseline systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C) on the risk of vascular outcomes in a large population of patients at high risk of future cardiovascular events.

Methods: Data were pooled from the TNT (Treating to New Targets), CARDS (Collaborative Atorvastatin Diabetes Study), and IDEAL (Incremental Decrease in End-Points Through Aggressive Lipid Lowering) trials and included a total of 21,727 patients (TNT: 10,001; CARDS: 2838; IDEAL: 8888).

Relation Between Change in Renal Function and Cardiovascular Outcomes in Atorvastatin-Treated Patients (from the Treating to New Targets [TNT] Study).

Statins may have nephroprotective as well as cardioprotective effects in patients with cardiovascular disease. In the Treating to New Targets (TNT) study (NCT00327691), patients with coronary heart disease (CHD) were randomized to atorvastatin 10 or 80 mg/day and followed for 4.9 years.

Visit-to-visit low-density lipoprotein cholesterol variability and risk of cardiovascular outcomes: insights from the TNT trial.

Background: Studies demonstrate that lowering low-density lipoprotein cholesterol (LDL-C) using a statin is associated with significant reduction in cardiovascular events. Whether visit-to-visit variability in LDL-C levels affects cardiovascular outcomes is unknown.

Objectives: This study sought to evaluate the role of visit-to-visit variability in LDL-C levels on cardiovascular outcomes.

Cardiovascular event reduction versus new-onset diabetes during atorvastatin therapy: effect of baseline risk factors for diabetes.

Objectives: The purpose of this study was to compare the incidence of new-onset diabetes (NOD) with cardiovascular (CV) event reduction at different levels of NOD risk.

Background: Statins reduce the number of CV events but increase the incidence of NOD. We previously reported that 4 factors independently predicted NOD: fasting blood glucose >100 mg/dl, fasting triglycerides >150 mg/dl, body mass index >30 kg/m(2), and history of hypertension.

Determinants of residual risk in secondary prevention patients treated with high- versus low-dose statin therapy: the Treating to New Targets (TNT) study.

Background: Cardiovascular events occur among statin-treated patients, albeit at lower rates. Risk factors for this "residual risk" have not been studied comprehensively. We aimed to identify determinants of this risk above and beyond lipid-related risk factors.

Relation of improvement in estimated glomerular filtration rate with atorvastatin to reductions in hospitalizations for heart failure (from the Treating to New Targets [TNT] study).

Impaired kidney function often accompanies heart failure (HF) and is associated with a worse prognosis. This post hoc analysis of the Treating to New Targets (TNT) trial examined whether the observed decrease in HF hospitalizations with high- compared to low-dose atorvastatin could be related to improvements in kidney function. Of 10,001 TNT participants, 9,376 had estimated glomerular filtration rate (eGFR) measurements at baseline and 1 year and were included in this analysis.

Effect of torcetrapib on glucose, insulin, and hemoglobin A1c in subjects in the Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events (ILLUMINATE) trial.

Background: High-density lipoproteins have antidiabetic properties in vitro. Furthermore, elevated high-density lipoprotein levels accompanying a genetic deficiency of cholesteryl ester transfer protein are associated with decreased levels of plasma glucose. We now investigate effects on glucose homeostasis of inhibiting cholesteryl ester transfer protein with torcetrapib.

Predictors of new-onset diabetes in patients treated with atorvastatin: results from 3 large randomized clinical trials.

Objectives: We sought to examine the incidence and clinical predictors of new-onset type 2 diabetes mellitus (T2DM) within 3 large randomized trials with atorvastatin.

Background: Statin therapy might modestly increase the risk of new-onset T2DM.

Methods: We used a standard definition of diabetes and excluded patients with prevalent diabetes at baseline.

Impact of smoking on cardiovascular events in patients with coronary disease receiving contemporary medical therapy (from the Treating to New Targets [TNT] and the Incremental Decrease in End Points Through Aggressive Lipid Lowering [IDEAL] trials).

To define the incremental risk of cigarette smoking in patients with coronary disease receiving contemporary medical therapy, we performed a post hoc analysis of 18,885 patients by combining data from the Treating to New Targets (TNT) and the Incremental Decrease in End Points through Aggressive Lipid Lowering (IDEAL) trials. These studies compared high-dose treatment (atorvastatin 80 mg/day) to moderate-dose treatment (atorvastatin 10 mg/day in TNT and simvastatin 20 to 40 mg/day in IDEAL) in patients with established coronary heart disease. The primary end point of this pooled analysis was major cardiovascular events, a composite of cardiac death, myocardial infarction, stroke, or resuscitated cardiac arrest.

Usefulness of heart rate at rest as a predictor of mortality, hospitalization for heart failure, myocardial infarction, and stroke in patients with stable coronary heart disease (Data from the Treating to New Targets [TNT] trial).

The heart rate at rest (HR) is a predictor of cardiovascular (CV) mortality. However, its effect on nonfatal CV events is unknown. The aim of the present post hoc analysis of the Treating New Targets (TNT) trial was to assess the effect of the HR at rest on major CV events in patients with stable coronary heart disease.

Comparison of 80 versus 10 mg of atorvastatin on occurrence of cardiovascular events after the first event (from the Treating to New Targets [TNT] trial).

Analyses of randomized clinical trials are usually restricted to examination of time to first event. However, because many patients have multiple events, this approach precludes much potentially useful clinical and economic data. To assess the effect on overall disease burden in the Treating to New Targets (TNT) study, we evaluated the effect of treatment with atorvastatin 80 versus 10 mg in the period after the occurrence of a first cardiovascular event.

Comparison of effectiveness of atorvastatin 10 mg versus 80 mg in reducing major cardiovascular events and repeat revascularization in patients with previous percutaneous coronary intervention (post hoc analysis of the Treating to New Targets [TNT] Study).

The Treating to New Targets (TNT) study demonstrated that intensive atorvastatin therapy to achieve low-density lipoprotein cholesterol concentrations well below recommended target levels provides an incremental clinical benefit in patients with stable coronary artery disease. This post hoc analysis of the TNT study was conducted to investigate whether this benefit extends to patients with previous percutaneous coronary intervention (PCI). A total of 10,001 patients with clinically evident coronary artery disease, including 5,407 patients with previous PCI, were randomized to atorvastatin 10 or 80 mg/day and followed for a median of 4.

Intensive lipid lowering with atorvastatin in patients with coronary artery disease, diabetes, and chronic kidney disease.

Objective: To investigate the effect of intensive lipid lowering with high-dose atorvastatin on the incidence of major cardiovascular events compared with low-dose atorvastatin in patients with coronary artery disease and type 2 diabetes, with and without chronic kidney disease (CKD).

Patients And Methods: Following 8 weeks' open-label therapy with atorvastatin (10 mg/d), 10,001 patients with coronary artery disease were randomized to receive double-blind therapy with either 80 mg/d or 10 mg/d of atorvastatin between July 1, 1998, and December 31, 1999. Of 1501 patients with diabetes, renal data were available for 1431.

The Atorvastatin/Donepezil in Alzheimer's Disease Study (LEADe): design and baseline characteristics.

Background: Growing evidence suggests that elevated cholesterol levels in mid-life are associated with increased risk of developing Alzheimer's disease (AD), and that statins might have a protective effect against AD and dementia. The Lipitor's Effect in Alzheimer's Dementia (LEADe) study tests the hypothesis that a statin (atorvastatin 80 mg daily) will provide a benefit on the course of mild to moderate AD in patients receiving background therapy of a cholinesterase inhibitor (donepezil 10 mg daily).

Methods: This is an international, multicenter, double-blind, randomized, parallel-group study with a double-blind randomized withdrawal phase of patients with mild to moderate AD (Mini-Mental State Examination [MMSE] score, 13 to 25).

Intensive lipid-lowering with atorvastatin for secondary prevention in patients after coronary artery bypass surgery.

Objectives: The aim of this post hoc analysis from the TNT (Treating to New Targets) trial is to determine whether patients with previous coronary artery bypass grafting (CABG) surgery achieved clinical benefit from intensive low-density lipoprotein (LDL)-cholesterol lowering.

Background: The development and progression of atherosclerosis is accelerated in coronary venous bypass grafts.

Methods: A total of 10,001 patients with documented coronary disease, including 4,654 with previous CABG, were randomized to atorvastatin 80 or 10 mg/day and were followed for a median of 4.

The benefits of intensive lipid lowering in patients with stable coronary heart disease with normal or high systolic blood pressure: an analysis of the Treating to New Targets (TNT) study.

This post-hoc analysis of the Treating to New Targets (TNT) study evaluated the joint effects of managing low-density lipoprotein cholesterol (LDL-C) and systolic blood pressure (SBP) on cardiovascular outcomes. Patients (N=9739) with clinically evident, stable coronary heart disease (CHD) were randomized to atorvastatin 10 or 80 mg/d. The primary end point was occurrence of a first major cardiovascular event.

Intensive lipid lowering with atorvastatin in patients with coronary heart disease and chronic kidney disease: the TNT (Treating to New Targets) study.

Objectives: This subanalysis of the TNT (Treating to New Targets) study investigates the effects of intensive lipid lowering with atorvastatin in patients with coronary heart disease (CHD) with and without pre-existing chronic kidney disease (CKD).

Background: Cardiovascular disease is a major cause of morbidity and mortality in patients with CKD.

Methods: A total of 10,001 patients with CHD were randomized to double-blind therapy with atorvastatin 80 mg/day or 10 mg/day.

Effect of intensive lipid lowering with atorvastatin on renal function in patients with coronary heart disease: the Treating to New Targets (TNT) study.

Background And Objectives: Data suggest that atorvastatin may be nephroprotective. This subanalysis of the Treating to New Targets study investigated how intensive lipid lowering with 80 mg of atorvastatin affects renal function when compared with 10 mg in patients with coronary heart disease.

Design, Setting, Participants, & Measurements: A total of 10,001 patients with coronary heart disease and LDL cholesterol levels of <130 mg/dl were randomly assigned to double-blind therapy with 10 or 80 mg/d atorvastatin.

Effects of high-dose atorvastatin on cerebrovascular events in patients with stable coronary disease in the TNT (treating to new targets) study.

Objective: We sought to assess the effects on cerebrovascular events of treating patients with stable coronary disease with low-density lipoprotein cholesterol (LDL-C) levels substantially below 100 mg/dl.

Background: Lowering LDL-C with statins has been shown to reduce the risk of stroke in patients with stable coronary disease. In observational studies, naturally low cholesterol levels have been associated with an increased risk of hemorrhagic stroke.

Effect of lowering LDL cholesterol substantially below currently recommended levels in patients with coronary heart disease and diabetes: the Treating to New Targets (TNT) study.

Objective: The Treating to New Targets study showed that intensive lipid-lowering therapy with atorvastatin 80 mg/day provides significant clinical benefit beyond that afforded by atorvastatin 10 mg/day in patients with stable coronary heart disease (CHD). The objective of our study was to investigate whether similar benefits of high-dose intensive atorvastatin therapy can be achieved in patients with CHD and diabetes.

Research Design And Methods: A total of 1,501 patients with diabetes and CHD, with LDL cholesterol levels of <130 mg/dl, were randomized to double-blind therapy with either atorvastatin 10 (n = 753) or 80 (n = 748) mg/day.