Cost-Effectiveness of Bempedoic Acid in High Cardiovascular Risk Patients with Statin Intolerance: An Analysis of the CLEAR Outcomes Trial.

Background: In the CLEAR Outcomes study, 13,970 high cardiovascular risk patients with hypercholesterolemia and statin intolerance were randomized to treatment with bempedoic acid or standard of care (placebo). Bempedoic acid reduced the risk of major adverse cardiovascular events by 13%. However, the cost-effectiveness of bempedoic acid in this patient population is unknown.

Coronary Stent Infection in Acute Double Valve Endocarditis.

We present a patient with aortic and mitral valve endocarditis who presented with acute ST-segment elevation myocardial infarction. The patient underwent percutaneous coronary intervention, aspiration thrombectomy, and stent placement. A transthoracic echocardiogram subsequently revealed endocarditis.

Association of testosterone-induced increase in neutrophil and monocyte counts with thromboembolic events: The TRAVERSE trial.

Background: In epidemiological studies, higher leukocyte and platelet counts are associated with increased risk of cardiovascular events. Effects of testosterone replacement therapy (TRT) on leukocyte subsets and platelets in men with hypogonadism and association of circulating leukocyte subtypes and platelets during TRT with cardiovascular events remain unknown.

Methods: In the TRAVERSE Trial, 5,204 men, 45-80 years with hypogonadism and preexisting or increased risk of cardiovascular disease (CVD) were randomized to transdermal testosterone or placebo gel daily for up to 5 years.

Design and Rationale of Lp(a)HORIZON Trial: Assessing the Effect of Lipoprotein(a) Lowering With Pelacarsen on Major Cardiovascular Events in Patients With CVD and Elevated Lp(a).

Background: Lipoprotein(a), abbreviated Lp(a), consists of apolipoprotein B-100 covalently bound to apolipoprotein(a), and represents an independent, genetically-determined, causal risk factor for atherosclerotic cardiovascular disease (CVD) and calcific aortic stenosis. More than 20% of the world CVD population has elevated Lp(a). Currently there are no approved pharmacologic treatments to lower Lp(a) levels, and no randomized trials have demonstrated that lowering Lp(a) reduces CVD risk.

The Composite Number Needed to Treat for Semaglutide in Populations with Overweight or Obesity and Established Cardiovascular Disease Without Diabetes.

Introduction: Number needed to treat (NNT), an outcome measure derived from the estimated risk results of clinical trials, is widely used to demonstrate value to stakeholders by identifying how many patients require treatment to avoid one event of interest. However, NNTs calculated for primary trial endpoints may underestimate a treatment's value by not considering other outcomes. In this secondary analysis of data from the SELECT cardiovascular (CV) outcomes trial, we aimed to determine the NNT for semaglutide for major adverse cardiovascular events (MACE), in addition to NNTs when other clinically and payer-relevant outcomes are included.

Safety profile of semaglutide versus placebo in the SELECT study: a randomized controlled trial.

Objective: The objective of this study was to assess safety of once-weekly subcutaneous semaglutide 2.4 mg versus placebo, beyond reduction in major adverse cardiovascular events, in patients with established cardiovascular disease and overweight or obesity.

Methods: Safety data focused on serious adverse events (SAEs), all adverse events (AEs) leading to permanent treatment discontinuation irrespective of seriousness, and prespecified AEs of special interest irrespective of seriousness.

Characteristics and outcomes of patients with and without statin-associated muscle symptoms treated with bempedoic acid in the CLEAR Outcomes trial.

Background: Cholesterol Lowering via bEmpedoic Acid Regimen (CLEAR) outcomes, a randomized, double-blind, placebo-controlled cardiovascular outcomes trial, and the largest prospective database of patients with statin intolerance (SI), demonstrated that bempedoic acid reduces low-density lipoprotein cholesterol and cardiovascular risk in patients at high cardiovascular risk.

Objective: Assess baseline differences in SI symptoms and whether these influenced the clinical course during CLEAR outcomes.

Methods: Symptoms and impact of SI on daily living were recorded prior to randomization.

Bempedoic Acid for Prevention of Cardiovascular Events in People With Obesity: A CLEAR Outcomes Subset Analysis.

Background: Obesity and hypercholesterolemia independently increase cardiovascular disease risk. This analysis evaluated the efficacy and safety of bempedoic acid in people with obesity participating in the CLEAR (Cholesterol Lowering via Bempedoic Acid [ECT1002], an ACL-Inhibiting Regimen) Outcomes trial.

Methods: CLEAR Outcomes randomized 13 970 patients to daily bempedoic acid 180 mg or placebo.

Testosterone Replacement Therapy and Risk of COVID-19 and Effect of COVID-19 on Testosterone's Treatment Effect.

Context: Whether circulating testosterone, dihydrotestosterone, and estradiol levels or testosterone replacement therapy (TRT) affects the risk of COVID-19 and whether COVID-19 affects response to TRT remains unknown.

Objective: The study evaluated whether baseline testosterone, dihydrotestosterone, and estradiol levels or TRT are associated with risk of developing COVID-19 and whether COVID-19 affects treatment response to TRT.

Methods: Among 5204 men, aged 45 to 80 years, with hypogonadism in the TRAVERSE trial, 379 developed COVID-19.

Cost-effectiveness of semaglutide in people with obesity and cardiovascular disease without diabetes.

Aims: The cardioprotective effects of semaglutide 2.4 mg reported in the SELECT cardiovascular (CV) outcomes trial (ClinicalTrials.gov NCT03574597) provide clinical benefit for subjects with overweight or obesity and established CV disease without type 2 diabetes (T2D).

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.

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.