Heart failure outcomes captured by adverse event reporting in participants with type 2 diabetes and atherosclerotic cardiovascular disease: Observations from the VERTIS CV trial.

Aims: In VERTIS CV, ertugliflozin was associated with a 30% risk reduction for adjudication-confirmed, first and total hospitalizations for heart failure (HHF) in participants with type 2 diabetes and atherosclerotic cardiovascular disease. We evaluated the impact of ertugliflozin on the broader spectrum of all reported heart failure (HF) events independent of adjudication confirmation.

Methods And Results: Data from participants who received ertugliflozin (5 or 15 mg) were pooled and compared versus placebo.

Long-term weight loss and cardiorenal outcomes by baseline BMI in the VERTIS CV trial.

Aim: To assess weight loss and cardiorenal outcomes by baseline body mass index (BMI) in VERTIS CV.

Methods: Patients with type 2 diabetes and atherosclerotic cardiovascular (CV) disease were randomized to ertugliflozin or placebo. These post hoc analyses evaluated cardiometabolic and cardiorenal outcomes (a composite of death from CV causes or hospitalization for heart failure [HHF], CV death, HHF and an exploratory composite kidney outcome including ≥40% estimated glomerular filtration rate [eGFR] decrease) by baseline BMI, using conventional clinical categories and Cox proportional hazards models.

Addressing residual risk beyond statin therapy: New targets in the management of dyslipidaemias-A report from the European Society of Cardiology Cardiovascular Round Table.

Cardiovascular (CV) disease is the most common cause of death in Europe. Despite proven benefits, use of lipid-lowering therapy remains suboptimal. Treatment goals are often not achieved, even in patients at high risk with atherosclerotic CV disease (ASCVD).

Effects of ertugliflozin on uric acid and gout-related outcomes in persons with type 2 diabetes and cardiovascular disease: Post hoc analyses from VERTIS CV.

Aim: To conduct post hoc analyses of the VERTIS CV (NCT01986881) trial to explore the effects of ertugliflozin on serum uric acid (UA) and gout-related outcomes.

Materials And Methods: Participants with type 2 diabetes and atherosclerotic cardiovascular disease were randomised (1:1:1) to placebo, ertugliflozin 5 mg or ertugliflozin 15 mg. Mean UA over time (260 weeks) was evaluated for pooled ertugliflozin versus placebo overall, and by baseline quintile of UA (≤4.

Efficacy and Safety of Ertugliflozin Added to Metformin: A Pooled Population from Asia with Type 2 Diabetes and Overweight or Obesity.

Introduction: The efficacy and safety of ertugliflozin have not been well characterized in Asian populations with type 2 diabetes (T2D) and overweight or obesity as defined by the Chinese Diabetes Society [body mass index (BMI) ≥ 24 kg/m].

Methods: These post hoc analyses of pooled data from two randomized, double-blind, 26-week studies assessed the efficacy and safety of ertugliflozin (5 mg or 15 mg) compared with placebo in participants from Asia with T2D and baseline BMI ≥ 24 kg/m, with inadequate glycemic control on metformin. Longitudinal analyses were used to calculate least squares (LS) mean [95% confidence interval (CI)] change from baseline in glycemic indices and body weight.

Cardiorenal outcomes by indices of liver steatosis and fibrosis in individuals with type 2 diabetes and atherosclerotic cardiovascular disease: Analyses from VERTIS CV, a randomized trial of the sodium-glucose cotransporter-2 inhibitor ertugliflozin.

Aim: To conduct a post hoc analysis to explore indices of hepatic steatosis/fibrosis and cardiorenal outcomes in the VERTIS CV study.

Materials And Methods: Patients with type 2 diabetes and atherosclerotic cardiovascular (CV) disease were randomized to ertugliflozin or placebo. Liver steatosis and fibrosis were assessed post hoc using the hepatic steatosis index (HSI) and fibrosis-4 (FIB-4) index to explore associations with cardiorenal outcomes (ertugliflozin and placebo data pooled, intention-to-treat analysis set).

Mediators of ertugliflozin effects on heart failure and kidney outcomes among patients with type 2 diabetes mellitus.

Aims: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to reduce the risk of hospitalization for heart failure (HHF) and composite kidney outcomes, but the mediators underlying these benefits are unknown.

Materials And Methods: Among participants from VERTIS CV, a trial of patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease randomized to ertugliflozin versus placebo, Cox proportional hazards regression models were used to evaluate the percentage mediation of ertugliflozin efficacy on the first HHF and kidney composite outcome in 26 potential mediators. Time-dependent approaches were used to evaluate associations between early (change from baseline to the first post-baseline measurement) and average (weighted average of change from baseline using all post-baseline measurements) changes in covariates with clinical outcomes.

Ertugliflozin and incident obstructive sleep apnea: an analysis from the VERTIS CV trial.

Purpose: The sodium-glucose transporter 2 inhibitor (SGLT2i) empagliflozin may reduce the incidence of obstructive sleep apnea (OSA) in patients with type 2 diabetes (T2D) and cardiovascular (CV) disease. This analysis of VERTIS CV, the CV outcome trial for the SGLT2i ertugliflozin conducted in a similar group of patients, explored the effects of ertugliflozin on reported incident OSA.

Methods: In VERTIS CV, patients ≥ 40 years with T2D and atherosclerotic CV disease (ASCVD) were randomized to ertugliflozin 5 or 15 mg or placebo.

Efficacy of Ertugliflozin on Heart Failure-Related Events in Patients With Type 2 Diabetes Mellitus and Established Atherosclerotic Cardiovascular Disease: Results of the VERTIS CV Trial.

Background: In patients with type 2 diabetes mellitus, sodium-glucose cotransporter 2 inhibitors reduce the risk of hospitalization for heart failure (HHF). We assessed the effect of ertugliflozin on HHF and related outcomes.

Methods: VERTIS CV (Evaluation of Ertugliflozin Efficacy and Safety Cardiovascular Outcomes Trial), a double-blind, placebo-controlled trial, randomly assigned patients with type 2 diabetes mellitus and atherosclerotic cardiovascular (CV) disease to once-daily ertugliflozin 5 mg, 15 mg, or placebo.

Efficacy and safety of ertugliflozin in East/Southeast Asian patients with type 2 diabetes mellitus.

Aim: Post-hoc analysis of the efficacy and safety of ertugliflozin in East/Southeast (E/SE) Asian patients with type 2 diabetes mellitus (T2DM).

Materials And Methods: Efficacy evaluations used data from randomized, double-blind, phase 3 studies: a pool of two 26-week placebo-controlled studies and one 52-week active-comparator (glimepiride) study. Least squares mean change from baseline was calculated for HbA1c, fasting plasma glucose (FPG), body weight (BW) and systolic blood pressure (SBP).

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.

Comparison of atorvastatin 80 mg/day versus simvastatin 20 to 40 mg/day on frequency of cardiovascular events late (five years) after acute myocardial infarction (from the Incremental Decrease in End Points through Aggressive Lipid Lowering [IDEAL] trial).

Previous studies have demonstrated that benefits of intensive statin therapy compared to standard statin therapy begin shortly after an acute event and are continued up to 2 years of follow-up. However, whether efficacy and safety of intensive statin therapy in patients with a recent cardiac event are maintained in longer-term follow-up has not been evaluated. We conducted a post hoc analysis of a subgroup of 999 patients who had a first acute myocardial infarction (MI) <2 months before randomization in a prospective, open-label, blinded end-point evaluation trial of 8,888 patients with a history of MI that compared intensive statin therapy (atorvastatin 80 mg) to standard statin therapy (simvastatin 20 to 40 mg) over approximately 5 years of follow-up.

Total cardiovascular disease burden: comparing intensive with moderate statin therapy insights from the IDEAL (Incremental Decrease in End Points Through Aggressive Lipid Lowering) trial.

Objectives: This post-hoc analysis of the IDEAL (Incremental Decrease in End Points Through Aggressive Lipid Lowering) trial was designed to assess the comparative treatment efficacy of high-dose atorvastatin and usual-dose simvastatin for the prevention of events subsequent to the first event, using the Wei, Lin, and Weissfeld method.

Background: Time-to-first-event analysis of data is frequently utilized to provide efficacy outcome information in coronary heart disease prevention trials. However, during the course of such long-term trials, a large number of events occur subsequent to the first event, the analysis of which will be precluded by this approach.

Adherence-adjusted efficacy with intensive versus standard statin therapy in patients with acute myocardial infarction in the IDEAL study.

Background: The Incremental Decrease in End Points through Aggressive Lipid Lowering trial showed that the primary endpoint major coronary event was reduced by 11% (0.78-1.01) using atorvastatin 80 mg versus simvastatin 20-40 mg in patients with coronary heart disease (P=0.

Comparison of efficacy and safety of atorvastatin (80 mg) to simvastatin (20 to 40 mg) in patients aged <65 versus >or=65 years with coronary heart disease (from the Incremental DEcrease through Aggressive Lipid Lowering [IDEAL] study).

The efficacy and safety of atorvastatin (80 mg/day) versus simvastatin (20 to 40 mg/day) in older (age >or=65 years) versus younger (<65 years) patients were assessed in a prespecified secondary analysis of the 8,888 patients with myocardial infarction in the IDEAL trial, a randomized open-label study. Several cardiovascular end points were evaluated, including the occurrence of a first major coronary event (MCE; nonfatal myocardial infarction, coronary heart disease death, or resuscitated cardiac arrest), the primary end point of the trial, and occurrence of any cardiovascular event (MCE, stroke, revascularization, unstable angina, congestive heart failure, and peripheral artery disease). Although there were no significant interactions between age and treatment, the magnitude of effect in favor of atorvastatin was higher in younger versus older patients (occurrence of first MCE, hazard ratio [HR] 0.

Lipoprotein predictors of cardiovascular events in statin-treated patients with coronary heart disease. Insights from the Incremental Decrease In End-points Through Aggressive Lipid-lowering Trial (IDEAL).

Background: Few studies have looked into the ability of measurements of apolipoprotein B (apoB) and apolipoprotein A-1 (apoA-1) or apoB/apoA-1 to predict new coronary heart disease (CHD) events in patients with CHD on statin treatment.

Aims: In the IDEAL trial, to compare lipoprotein components to predict CHD events and to what degree differences in those parameters could explain the observed outcome.

Methods: We compared the ability of treatment with atorvastatin 80 mg/day to that of simvastatin 20-40 mg/day to prevent CHD events in patients with CHD and used Cox regression models to study the relationships between on-treatment levels of lipoprotein components to subsequent major coronary events (MCE).

Lipids, apolipoproteins, and their ratios in relation to cardiovascular events with statin treatment.

Background: Low-density lipoprotein (LDL) cholesterol is the principal target of lipid-lowering therapy, but recent evidence has suggested more appropriate targets. We compared the relationships of on-treatment levels of LDL cholesterol, non-high-density lipoprotein (HDL) cholesterol, and apolipoprotein B, as well as ratios of total/HDL cholesterol, LDL/HDL cholesterol, and apolipoprotein B/A-I, with the occurrence of cardiovascular events in patients receiving statin therapy.

Methods And Results: A post hoc analysis was performed that combined data from 2 prospective, randomized clinical trials in which 10,001 ("Treating to New Targets") and 8888 ("Incremental Decrease in End Points through Aggressive Lipid Lowering") patients with established coronary heart disease were assigned to usual-dose or high-dose statin treatment.

Responsiveness of plasma lipids and lipoproteins to plant stanol esters.

Plant stanols have been shown to reduce serum levels of low-density lipoprotein (LDL) cholesterol, and they are an attractive adjunct in dietary therapy for elevated LDL cholesterol. This investigation addressed 3 questions through metabolic studies in human subjects: (1) whether plant stanol esters given at higher doses than the 2-g/day dose recommended by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) will provide additional LDL-lowering efficacy (study 1); (2) whether substantial reduction in LDL cholesterol can be obtained in postmenopausal women with hypercholesterolemia by addition of plant stanol esters to the diet (study 2); and (3) whether ATP III goals can be obtained by adding plant stanol esters to an LDL-lowering regimen in high-risk patients who retain LDL cholesterol levels in the above-optimal range (ie, 2.6 to 3.

Influence of extended-release nicotinic acid on nonesterified fatty acid flux in the metabolic syndrome with atherogenic dyslipidemia.

Nicotinic acid has favorable effects on atherogenic dyslipidemia. However, in some patients who have diabetes, crystalline nicotinic acid decreases glycemic control; this effect could be due to a marked rebound of nonesterified fatty acids (NEFAs) observed after nicotinic acid suppression of lipolysis in adipose tissue. Recent reports have indicated that small doses of extended-release nicotinic acid do not cause a substantial decrease in glucose levels.

Free fatty acid metabolism during fenofibrate treatment of the metabolic syndrome.

Objective: Our objective was to determine whether fenofibrate modifies the metabolism of nonesterified (free) fatty acids as a component of its triglyceride-lowering action in male patients with the metabolic syndrome.

Design: In a placebo-controlled trial lasting 16 weeks, patients were randomly assigned to fenofibrate (200 mg/d) or placebo for 8 weeks. They were then crossed over to placebo or treatment with fenofibrate for another 8 weeks.

Effects of adding fenofibrate (200 mg/day) to simvastatin (10 mg/day) in patients with combined hyperlipidemia and metabolic syndrome.

Combined hyperlipidemia predisposes subjects to coronary heart disease. Two lipid abnormalities--increased cholesterol and atherogenic dyslipidemia--are potential targets of lipid-lowering therapy. Successful management of both may require combined drug therapy.

The effect of dietary intervention on serum lipid levels in type 2 diabetes mellitus.

Dietary therapy is the cornerstone of lipid management in patients with type 2 diabetes mellitus. The key strategies are the reduction of intake of saturated fat, trans unsaturated fat and cholesterol, and the reduction of energy intake to promote weight loss. This approach will produce significant improvements in the serum levels of low-density lipoprotein (LDL) cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol.