Explore the vast range of titles available.

Randomized treatment comparing an intensive glycemic treatment strategy with a standard strategy in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial was ended early because of an unexpected excess of mortality in the intensive arm. As part of ongoing post hoc analyses of potential mechanisms for this finding, we explored whether on-treatment A1C itself had an independent relationship with mortality. Participants with type 2 diabetes (n = 10,251 with mean age 62 years, median duration of diabetes 10 years, and median A1C 8.1%) were randomly assigned to treatment strategies targeting either A1C <6.0% (intensive) or A1C 7.0-7.9% (standard). Data obtained during 3.4 (median) years of follow-up before cessation of intensive treatment were analyzed using several multivariable models. Various characteristics of the participants and the study sites at baseline had significant associations with the risk of mortality. Before and after adjustment for these covariates, a higher average on-treatment A1C was a stronger predictor of mortality than the A1C for the last interval of follow-up or the decrease of A1C in the first year. Higher average A1C was associated with greater risk of death. The risk of death with the intensive strategy increased approximately linearly from 6-9% A1C and appeared to be greater with the intensive than with the standard strategy only when average A1C was >7%. These analyses implicate factors associated with persisting higher A1C levels, rather than low A1C per se, as likely contributors to the increased mortality risk associated with the intensive glycemic treatment strategy in ACCORD.

Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Furthermore, patients with T2DM and acute coronary syndrome (ACS) have a particularly high risk of CV events. The glucagon-like peptide 1 receptor agonist, lixisenatide, improves glycemia, but its effects on CV events have not been thoroughly evaluated. ELIXA (www.clinicaltrials.gov no. NCT01147250) is a randomized, double-blind, placebo-controlled, parallel-group, multicenter study of lixisenatide in patients with T2DM and a recent ACS event. The primary aim is to evaluate the effects of lixisenatide on CV morbidity and mortality in a population at high CV risk. The primary efficacy end point is a composite of time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. Data are systematically collected for safety outcomes, including hypoglycemia, pancreatitis, and malignancy. Enrollment began in July 2010 and ended in August 2013; 6,068 patients from 49 countries were randomized. Of these, 69% are men and 75% are white; at baseline, the mean ± SD age was 60.3 ± 9.7 years, body mass index was 30.2 ± 5.7 kg/m2, and duration of T2DM was 9.3 ± 8.2 years. The qualifying ACS was a myocardial infarction in 83% and unstable angina in 17%. The study will continue until the positive adjudication of the protocol-specified number of primary CV events. ELIXA will be the first trial to report the safety and efficacy of a glucagon-like peptide 1 receptor agonist in people with T2DM and high CV event risk.

In this clinical trial involving patients with established cardiovascular disease, the addition of niacin to intensive statin therapy provided no additional clinical benefit over a period of 3 years, despite favorable changes in lipid levels. More than 18 million North Americans have coronary heart disease, and despite profound advances in both pharmacologic and interventional management, both morbidity and mortality remain appreciable. 1 , 2 Elevated low-density lipoprotein (LDL) cholesterol levels are an established predictor of the risk of coronary heart disease. Multiple primary and secondary prevention trials have shown a significant reduction of 25 to 35% in the risk of cardiovascular events with statin therapy 3 ; however, residual risk persists despite the achievement of target LDL cholesterol levels. Epidemiologic studies have shown that, in addition to elevated LDL cholesterol levels, low levels of high-density lipoprotein (HDL) cholesterol . . .

In this trial, 3445 patients with heart failure and a preserved ejection fraction were assigned to spironolactone or placebo. At a mean of 3.3 years, there was no significant difference in death from cardiovascular causes, aborted cardiac arrest, or hospitalization for heart failure. Many patients with heart failure have a normal or near-normal left ventricular ejection fraction. 1 – 4 Such patients share common signs and symptoms, as well as an impaired quality of life and a poor prognosis, with patients who have heart failure and a reduced ejection fraction. 5 – 8 However, the benefit of most medical therapies for heart failure is limited to those with a reduced ejection fraction, generally 40% or less. 1 , 2 , 9 The lack of favorable evidence from clinical-outcome trials involving patients with heart failure and a preserved left ventricular ejection fraction is reflected in current guidelines, which offer no specific . . .

In this randomized study, the addition of lixisenatide, a glucagon-like peptide 1–receptor agonist, to usual care in patients with type 2 diabetes and a recent cardiovascular event did not alter the rate of subsequent major cardiovascular or other serious adverse events. Randomized trials involving patients with new or established type 2 diabetes have shown that improved glucose control reduces the risk of microvascular complications, 1 – 3 with modest cardiovascular benefits suggested by meta-analyses and extended follow-up of clinical trials. 4 – 7 However, various studies indicate that, despite being effective in lowering the glucose and glycated hemoglobin levels, some hypoglycemic medications may increase, rather than reduce, the risk of cardiovascular events. 8 – 10 These unexpected findings prompted the reexamination of the regulatory approval processes for new antidiabetic therapies, which had been based primarily on the surrogate measure of glucose lowering with limited clinical-outcomes data. Since . . .

Introduction. We investigated the association of diabetic retinopathy and neuropathy with increased risk of recurrent cardiovascular (CV) events in 6068 patients with type 2 diabetes mellitus (T2DM) and recent acute coronary syndrome (ACS) enrolled in the Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA). Methods. History of retinopathy and neuropathy as well as duration of T2DM were self-reported at screening. Proportional hazards regression models were used to assess relationships between retinopathy, neuropathy, and recurrent CV events. Results. At screening, retinopathy and neuropathy were reported in 10.7% and 17.5% of patients, respectively, while 5.7% reported both. When adjusted for randomized treatment only, both retinopathy and neuropathy were associated with a primary composite outcome (CV death, nonfatal MI, stroke, or hospitalization for unstable angina) (retinopathy: HR 1.44, 95% CI 1.19–1.75; neuropathy: HR 1.33, 95% CI 1.12–1.57), CV composite (CV death, nonfatal MI, stroke, hospitalization for heart failure (HF)) (retinopathy: HR 1.57, 95% CI 1.31–1.88; neuropathy: HR 1.38, 95% CI 1.19–1.62), myocardial infarction (retinopathy: HR 1.38, 95% CI 1.08–1.76; neuropathy: HR 1.26, 95% CI 1.02–1.54), HF hospitalization (retinopathy: HR 2.03, 95% CI 1.48–2.78; neuropathy: HR 1.71, 95% CI 1.30–2.27), and all-cause mortality (retinopathy: HR 1.65, 95% CI 1.28–2.12; neuropathy: HR 1.43, 95% CI 1.14–1.78). When included in the same model, and adjusted for T2DM duration, there were no independent associations of either with CV outcomes, while T2DM duration remained strongly associated with all outcomes. Addition of demographic characteristics and CV risk factors did not further alter these relationships. Conclusions. In patients with T2DM and recent ACS, a history of retinopathy and/or neuropathy and longer T2DM duration could be considered clinical markers for high risk of recurrent CV events. This trial is registered with the ELIXA (Evaluation of Lixisenatide in Acute Coronary Syndrome), ClinicalTrials.gov registration number NCT01147250.

In a randomized trial, 4733 patients with type 2 diabetes mellitus who were at high risk for cardiovascular events received treatment aimed at a target systolic blood pressure of less than 120 mm Hg or less than 140 mm Hg. At a mean follow-up of 4.7 years, the rates of the primary end point (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) were not significantly different between the two trial groups. Patients with type 2 diabetes mellitus who were at high risk for cardiovascular events received treatment aimed at a target systolic blood pressure of less than 120 mm Hg or less than 140 mm Hg. At a mean follow-up of 4.7 years, the rates of the primary end point were not significantly different between the two groups. Diabetes mellitus increases the risk of cardiovascular disease by a factor of two to three at every level of systolic blood pressure. 1 Because cardiovascular risk in patients with diabetes is graded and continuous across the entire range of levels of systolic blood pressure, even at prehypertensive levels, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) recommended beginning drug treatment in patients with diabetes who have systolic blood pressures of 130 mm Hg or higher, with a treatment goal of reducing systolic blood pressure to below 130 mm Hg. . . .

In the ACCORD trial, a mean of 3.7 years of intensive glucose lowering increased mortality and reduced nonfatal myocardial infarctions after 5 years of follow-up. The therapy cannot be recommended for high-risk patients with advanced type 2 diabetes. Type 2 diabetes mellitus is a strong, independent risk factor for cardiovascular disease and death, 1 and many epidemiologic analyses have identified a progressive relationship between hyperglycemia and these outcomes. 2 – 5 The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial was designed to determine whether a strategy of targeting normal glycated hemoglobin levels (i.e., <6.0%) would reduce the risk of serious cardiovascular events in middle-aged and elderly people with type 2 diabetes mellitus, glycated hemoglobin levels of 7.5% or more, and additional cardiovascular risk factors. 6 However, on the basis of a mean of 3.5 years' worth of data, the independent . . .

Whether androgen deficiency among men increases the risk of cardiovascular (CV) events or is merely a disease marker remains a subject of intense scientific interest. Among male subjects in the AIM-HIGH Trial with metabolic syndrome and low baseline levels of high-density lipoprotein (HDL)-cholesterol who were randomized to niacin or placebo plus simvastatin, we examined the relationship between low baseline testosterone (T) concentrations and subsequent CV outcomes during a mean 3-year follow-up. In this post hoc analysis of men with available baseline plasma T concentrations, we examined the relationship between clinical/demographic characteristics and T concentrations both as a continuous and dichotomous variable (<300 ng/dL [“low T\"] vs. ≥300 ng/dL [“normal T\"]) on rates of pre-specified CV outcomes, using Cox proportional hazards models. Among 2118 male participants in whom T concentrations were measured, 643 (30%) had low T and 1475 had normal T concentrations at baseline. The low T group had higher rates of diabetes mellitus, hypertension, elevated body mass index, metabolic syndrome, higher blood glucose, hemoglobin A1c, and triglyceride levels, but lower levels of both low-density lipoprotein and HDL-cholesterol, and a lower rate of prior myocardial infarction (MI). Men with low T had a higher risk of the primary composite outcome of coronary heart disease (CHD) death, MI, stroke, hospitalization for acute coronary syndrome, or coronary or cerebral revascularization (20.1%) compared with the normal T group (15.2%); final adjusted HR 1.23, P = .07, and a higher risk of the CHD death, MI, and stroke composite endpoint (11.8% vs. 8.2%; final adjusted HR 1.37, P = .04), respectively. In this post hoc analysis, there was an association between low baseline testosterone concentrations and increased risk of subsequent CV events in androgen-deficient men with established CV disease and metabolic syndrome, particularly for the composite secondary endpoint of CHD death, MI, and stroke. In this AIM-HIGH Trial post hoc analysis of 2118 men with metabolic syndrome and low HDL-cholesterol with available baseline plasma testosterone (T) samples, 643 males (30%) had low T (mean: 229 ng/dL) and 1475 (70%) had normal T (mean: 444 ng/dL) concentrations. The “low T\" group had a 24% higher risk of the primary 5-component endpoint (20.1%) compared with the normal T group (15.2%); final adjusted HR 1.23, P = .07). There was also a 31% higher risk of the secondary composite endpoint: coronary heart disease death, myocardial infarction, and stroke (11.8% vs. 8.2%, final adjusted HR 1.37, P = .04) in the low vs. normal T group, respectively.

Erectile dysfunction (ED) is a common disorder in middle-aged men and is significantly influenced by cardiovascular risk factors (CVRFs) and cardiovascular disease. The substudy of the ONTARGET/TRANSCEND trials evaluates the relationship of erectile function to baseline characteristics and current treatment in cardiovascular high-risk patients who have been enrolled in these trials. The effects of treatment with telmisartan and ramipril, alone or in combination, including a telmisartan versus placebo arm will be determined prospectively during a follow-up of 4 years. One thousand three hundred fifty-seven patients were evaluated in 13 countries at baseline, 2 years, and 4 years, with ED determined using the ED score of the Cologne Male Survey (Kölner [Cologne] Evaluation of Erectile Dysfunction) and the 5-item International Index of Erectile Function. Erectile dysfunction scores were related to CVRF and the use of cardiovascular drugs. Prevalence of ED was 50.7% (Kölner [Cologne] Evaluation of Erectile Dysfunction) and 54.3% (5-item International Index of Erectile Function), respectively, with a decline of sexual activity after the diagnosis of cardiovascular disease. In multivariate analysis, diabetes mellitus ( P < .00001), stroke ( P = .00026), pelvic surgery ( P = .025), and age of >65 years ( P < .00001) correlated with the degree of ED. No significant associations were observed for cholesterol levels, hypertension, and smoking status as well as current treatment with angiotensin-converting enzyme inhibitors, angiotensin I antagonists, diuretics, β-blockers, or calcium-channel blockers. The ONTARGET/TRANSCEND-ED substudy shows a significant influence of cardiovascular disease on erectile function. In contrast to prior smaller studies, drug therapy and CVRF seem to play a minor role in cardiovascular high-risk patients. Follow-up data will provide information whether angiotensin-converting enzyme inhibitors, angiotensin I antagonists, or a combination thereof are able to improve erectile function.