ApoA-I Infusions and Burden of Ischemic Events After Acute Myocardial Infarction: Insights From the AEGIS-II Trial.

Background: Following an acute myocardial infarction (AMI), patients remain at risk for subsequent cardiovascular (CV) events. In the AEGIS-II trial, CSL112, a human apolipoprotein A-I derived from plasma that enhances cholesterol efflux, did not significantly reduce the first occurrence of CV death, myocardial infarction (MI), or stroke through 90 days compared with placebo. However, an analysis involving only the first event may not capture the totality of the clinical impact of an intervention because patients may experience multiple events.

Semaglutide versus placebo in patients with heart failure and mildly reduced or preserved ejection fraction: a pooled analysis of the SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM randomised trials.

Background: Heart failure with mildly reduced or preserved ejection fraction (hereafter referred to as HFpEF) is the most common type of heart failure and is associated with a high risk of hospitalisation and death, especially in patients with overweight, obesity, or type 2 diabetes. In the STEP-HFpEF and STEP-HFpEF DM trials, semaglutide improved heart failure-related symptoms and physical limitations in participants with HFpEF. Whether semaglutide also reduces clinical heart failure events in this group remains to be established.

Apolipoprotein A-I infusions and cardiovascular outcomes in acute myocardial infarction according to baseline LDL-cholesterol levels: the AEGIS-II trial.

Background And Aims: In the AEGIS-II trial (NCT03473223), CSL112, a human apolipoprotein A1 derived from plasma that increases cholesterol efflux capacity, did not significantly reduce the risk of the primary endpoint through 90 days vs. placebo after acute myocardial infarction (MI). Nevertheless, given the well-established relationship between higher low-density lipoprotein cholesterol (LDL-C) and plaque burden, as well as greater risk reductions seen with PCSK9 inhibitors in patients with baseline LDL-C ≥ 100 mg/dL on statin therapy, the efficacy of CSL112 may be influenced by baseline LDL-C.

The Effect of Semaglutide on Mortality and COVID-19-Related Deaths: An Analysis From the SELECT Trial.

Background: Patients with overweight and obesity are at increased risk of death from multiple causes, including cardiovascular (CV) death, with few therapies proven to reduce the risk.

Objectives: This study sought to assess the effect of semaglutide 2.4 mg on all-cause death, CV death, and non-CV death, including subcategories of death and death from coronavirus disease-2019 (COVID-19).

Comparative Cardiovascular Benefits of Bempedoic Acid and Statin Drugs.

Background: In the CLEAR (Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen) Outcomes trial, treatment of statin-intolerant patients with bempedoic acid produced a 21% decrease in low-density lipoprotein cholesterol (LDL-C) relative to placebo and a 13% relative reduction in the risk of major adverse cardiovascular events.

Objectives: This study sought to determine whether the relationship between LDL-C lowering and cardiovascular benefit achieved with bempedoic acid resembles that observed with statins when standardized per unit change in LDL-C.

Methods: To compare the treatment effect of bempedoic acid with statins, the methodology of the Cholesterol Treatment Trialists' Collaboration (CTTC) was applied to outcomes among the 13,970 patients enrolled in the CLEAR Outcomes trial.

Semaglutide and Cardiovascular Outcomes by Baseline HbA1c and Change in HbA1c in People With Overweight or Obesity but Without Diabetes in SELECT.

Objective: To evaluate the cardiovascular effects of semaglutide by baseline glycated hemoglobin (HbA1c) and change in HbA1c in a prespecified analysis of Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity (SELECT).

Research Design And Methods: In SELECT, people with overweight or obesity and atherosclerotic cardiovascular disease without diabetes were randomized to weekly semaglutide 2.4 mg or placebo.

Effect of Semaglutide on Regression and Progression of Glycemia in People With Overweight or Obesity but Without Diabetes in the SELECT Trial.

Objective: To determine whether semaglutide slows progression of glycemia in people with cardiovascular disease and overweight or obesity but without diabetes.

Research Design And Methods: In a multicenter, double-blind trial, participants aged ≥45 years, with BMI ≥27 kg/m2, and with preexisting cardiovascular disease but without diabetes (HbA1c <6.5%) were randomized to receive subcutaneous semaglutide (2.

Long-term kidney outcomes of semaglutide in obesity and cardiovascular disease in the SELECT trial.

The SELECT trial previously reported a 20% reduction in major adverse cardiovascular events with semaglutide (n = 8,803) versus placebo (n = 8,801) in patients with overweight/obesity and established cardiovascular disease, without diabetes. In the present study, we examined the effect of once-weekly semaglutide 2.4 mg on kidney outcomes in the SELECT trial.

Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial.

In the SELECT cardiovascular outcomes trial, semaglutide showed a 20% reduction in major adverse cardiovascular events in 17,604 adults with preexisting cardiovascular disease, overweight or obesity, without diabetes. Here in this prespecified analysis, we examined effects of semaglutide on weight and anthropometric outcomes, safety and tolerability by baseline body mass index (BMI). In patients treated with semaglutide, weight loss continued over 65 weeks and was sustained for up to 4 years.

Apolipoprotein A1 Infusions and Cardiovascular Outcomes after Acute Myocardial Infarction.

Background: Cardiovascular events frequently recur after acute myocardial infarction, and low cholesterol efflux - a process mediated by apolipoprotein A1, which is the main protein in high-density lipoprotein - has been associated with an increased risk of cardiovascular events. CSL112 is human apolipoprotein A1 derived from plasma that increases cholesterol efflux capacity. Whether infusions of CSL112 can reduce the risk of recurrent cardiovascular events after acute myocardial infarction is unclear.

Effect of Testosterone on Progression From Prediabetes to Diabetes in Men With Hypogonadism: A Substudy of the TRAVERSE Randomized Clinical Trial.

Importance: The effect of testosterone replacement therapy (TRT) in men with hypogonadism on the risk of progression from prediabetes to diabetes or of inducing glycemic remission in those with diabetes is unknown.

Objective: To evaluate the efficacy of TRT in preventing progression from prediabetes to diabetes in men with hypogonadism who had prediabetes and in inducing glycemic remission in those with diabetes.

Design, Setting, And Participants: This nested substudy, an intention-to-treat analysis, within a placebo-controlled randomized clinical trial (Testosterone Replacement Therapy for Assessment of Long-Term Vascular Events and Efficacy Response in Hypogonadal Men [TRAVERSE]) was conducted at 316 trial sites in the US.

Implementing a comprehensive STEMI protocol to improve care metrics and outcomes in patients with in-hospital STEMI: an observational cohort study.

Background: Patients who experience in-hospital ST-segment elevation myocardial infarction (iSTEMI) represent a uniquely high-risk cohort owing to delays in diagnosis, prolonged time to reperfusion and increased mortality. Quality initiatives aimed at improving the care of this vulnerable, yet understudied population are needed.

Methods: This study included consecutive patients with iSTEMI treated with percutaneous coronary intervention (PCI) between 1 January 2011 and 15 July 2019 at a single, tertiary referral centre.

Impact of Bempedoic Acid on Total Cardiovascular Events: A Prespecified Analysis of the CLEAR Outcomes Randomized Clinical Trial.

Importance: The ATP citrate lyase (ACL) inhibitor, bempedoic acid, reduces low-density lipoprotein cholesterol (LDL-C) level and major adverse cardiovascular events (MACE) by 13% in patients at high cardiovascular risk with intolerance of statin and high-intensity statin medications. The effects of bempedoic acid on total cardiovascular events remain unknown.

Objective: To determine the impact of bempedoic acid on the total incidence of MACE.

Coronary spasm and vasomotor dysfunction as a cause of MINOCA.

Increasing evidence has shown that coronary spasm and vasomotor dysfunction may be the underlying cause in more than half of myocardial infarctions with non-obstructive coronary arteries (MINOCA) as well as an important cause of chronic chest pain in the outpatient setting. We review the contemporary understanding of coronary spasm and related vasomotor dysfunction of the coronary arteries, the pathophysiology and prognosis, and current and emerging approaches to diagnosis and evidence-based treatment.

Depressive Syndromes in Men With Hypogonadism in the TRAVERSE Trial: Response to Testosterone-Replacement Therapy.

Context: The effect of testosterone on depressive symptoms in men with hypogonadism remains incompletely understood.

Objective: We assessed the effects of testosterone-replacement therapy (TRT) in improving depressive symptoms in hypogonadal men with and without depressive symptoms enrolled in the TRAVERSE cardiovascular safety trial.

Methods: A randomized, placebo-controlled, double-blind study was conducted at 316 trial sites.