Association of chronic neutrophil activation with risk of mortality.

BACKGROUND: Levels of free myeloperoxidase (MPO), a cardiovascular risk marker, have been reported to decline with standard care. Whether such declines signify decreased risk of mortality remains unknown. DESIGN: Cox proportional hazard models were generated using data from a retrospective cohort study of prospectively collected measures. PARTICIPANTS: Patients (3,658) who had MPO measurements and LDL-C ≥ 90 mg/dL during 2011-2015 were selected based on a stratified random sampling on MPO risk level. Baseline MPO was either low (<470 pmol/L), moderate (470-539 pmol/L), or high (≥540 pmol/L). MAIN OUTCOMES AND MEASURES: First occurrence of MACE (myocardial infarction, stroke, coronary revascularization, or all-cause death). RESULTS: Mean age was 66.5 years, and 64.7% were women. During a mean 6.5-year follow-up, crude incidence per 1000 patient years was driven by death. The incidence and all-cause death was highest for patients with high MPO (21.2; 95% CI, 19.0-23.7), then moderate (14.6; 95% CI, 11.5-18.5) and low (2.3; 95% CI, 1.2-4.6) MPO. After adjusting for age, sex, and cardiovascular risk factors, risk of cardiovascular death did not differ significantly between patients with high and low MPO (HR, 1.57; 95% CI, 0.56-4.39), but patients with high MPO had greater risk of non-cardiovascular (HR, 6.15; 95% CI, 2.27-16.64) and all-cause (HR, 3.83; 95% CI, 1.88-7.78) death. During follow-up, a 100 pmol/L decrease in MPO correlated with a 5% reduction in mortality (HR, 0.95; 95% CI, 0.93-0.97) over 5 years. CONCLUSIONS: Free circulating MPO is a strong marker of risk of mortality. Monitoring changes in MPO levels over time may provide insight into changes in physiology that mark a patient for increased risk of mortality.

Etripamil Nasal Spray: Therapeutic Potential for Treating Paroxysmal Supraventricular Tachycardia.

Patients with arrythmias are at an increased risk of heart-related comorbidities and complications. Specifically, patients with paroxysmal supraventricular tachycardia (PSVT), a type of arrythmia, are at increased risk of lightheadedness or shortness of breath, due to the increased rate of the heartbeat. Most patients are prescribed oral medications to control their heart rates and maintain a normal heart rhythm. Researchers have been tasked with discovering alternative treatment options with new delivery methods to treat arrythmias such as PSVT. A nasal spray was subsequently designed and is currently undergoing clinical studies. This review aims to present and discuss the current clinical and scientific evidence pertaining to etripamil.

A Review of the Clinical Pharmacology of Pelacarsen: A Lipoprotein(a)-Lowering Agent.

Patients with genetically associated elevated lipoprotein(a) [Lp(a)] levels are at greater risk for coronary artery disease, heart attack, stroke, and peripheral arterial disease. To date, there are no US FDA-approved drug therapies that are designed to target Lp(a) with the goal of lowering the Lp(a) level in patients who have increased risk. The American College of Cardiology (ACC) has provided guidelines on how to use traditional lipid profiles to assess the risk of atherosclerotic cardiovascular disease (ASCVD); however, even with the emergence of statin add-on therapies such as ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, some populations with elevated Lp(a) biomarkers remain at an increased risk for cardiovascular (CV) disease. Residual CV risk has led researchers to inquire about how lowering Lp(a) can be used as a potential preventative therapy in reducing CV events. This review aims to present and discuss the current clinical and scientific evidence pertaining to pelacarsen.

A Critical Review of the Efficacy and Safety of Inclisiran.

The association between low-density cholesterol (LDL-C) and cardiovascular disease (CVD) is well-established, with an emphasis on lowering LDL-C levels to reduce cardiovascular events. Statin therapy has been the traditional treatment for LDL-C reduction, in addition to lifestyle modifications, but studies have shown that a substantial proportion of patients does not reach target LDL-C goals despite receiving maximally tolerated statin medications. Additionally, statin therapy is associated with a few shortcomings as many patients initiated on these medications discontinue treatment within 1 year because of lack of tolerability. Furthermore, guidelines from both the American College of Cardiology and the American Heart Association highlight the importance of obtaining LDL-C goals because of the residual atherosclerotic CVD risk that remains in high-risk populations. That the residual cardiovascular risk remains despite statin therapy highlights the importance of evaluating therapeutic approaches that possess effective lipid lowering that can be used adjunctively with statins. Much focus has been directed towards the proprotein convertase subtilisin/kexin type 9 (PCSK9) pathway, leading to the development of evolocumab and alirocumab, two human monoclonal antibodies directed against PCSK9. These agents have been shown to markedly decrease LDL-C levels and significantly reduce cardiovascular risk, but the need for biweekly or monthly subcutaneous injections has generated concerns for patient compliance. A new pathway is being studied in which a synthetic small interfering ribonucleic acid (siRNA) targets the PCSK9 gene expressed in hepatocytes to prevent PCSK9 production. The siRNA, inclisiran sodium, significantly reduces hepatic production of PCSK9, causing a marked reduction in LDL-C levels, and exhibits sustained pharmacodynamic effects when dosed subcutaneously every 6 months. This review presents and discusses the current clinical and scientific evidence pertaining to inclisiran sodium.

A Review on the Efficacy and Safety of Oral Semaglutide.

There are numerous treatment options currently available for patients with type 2 diabetes mellitus; however, a multitude of patients continue to have inadequately controlled glycemic levels with their current antihyperglycemic regimen. Furthermore, the American Diabetes Association guidelines increasingly highlight the importance of multifactorial management and optimizing medication regimens that include cardiovascular, renal, and/or weight benefits in patients with type 2 diabetes mellitus. Glucagon-like peptide-1 receptor agonists belong to a novel class of type 2 diabetes mellitus agents that are becoming increasingly prevalent owing to their ability to improve glycemic status without the risk of hypoglycemia. Currently, there are three US Food and Drug Administration-approved glucagon-like peptide-1 receptor agonists, subcutaneous semaglutide, dulaglutide, and liraglutide, that also have an indication for reducing major adverse cardiovascular events in patients with type 2 diabetes mellitus and established cardiovascular disease. However, these agents are not often the first options because of their subcutaneous administration. Nevertheless, co-formulation of oral semaglutide with an absorption enhancer has shown to increase its bioavailability and has made its oral absorption possible. In the PIONEER trials, oral semaglutide effectively lowered blood glucose levels, and showed benefits on weight and cardiovascular outcomes; however, there is no Food and Drug Administration indication approved yet as the SOUL trial is still ongoing. Such characteristics of oral semaglutide may improve and increase its use compared to subcutaneous agents and possibly lead to earlier cardiovascular protection in addition to achieving glycemic control.

Efficacy, safety and cost-effectiveness comparison between U-100 human regular insulin and rapid acting insulin when delivered by V-Go wearable insulin delivery device in type 2 diabetes.

INTRODUCTION: We compared the efficacy and safety of human regular insulin (HRI) versus rapid-acting insulin (RAI) in a type 2 diabetes population already using the V-Go insulin delivery device. RESEARCH DESIGN AND METHODS: This was a 14-week, multicenter, randomized, open-label, parallel-group, phase IV, non-inferiority study. Patients ≥21years of age, with inadequately controlled type 2 diabetes who were currently using the V-Go insulin delivery system with RAI, with glycated hemoglobin (HbA1c) ≥6.5% (≥48 mmol/L) to ≤12.5% (≤108 mmol/L) were randomized 1:1 to RAI continuation or switch to HRI. The primary outcome was estimated treatment difference (ETD) in HbA1c least-squares mean change from baseline at 14 weeks (prespecified non-inferiority hypothesis with 95% CI upper limit <0.4%). Primary analysis was by per protocol (PP); safety analysis was by intention to treat. RESULTS: We randomized 136 patients to continued RAI treatment (n=67) or HRI (n=69); 113 patients were included in the PP analysis (RAI, n=54; HRI, n=59). Mean change in HbA1c from baseline to study end was -0.60±1.1% (95% CI -0.90 to -0.29); -6.6±12.0 mmol/mol (95% CI -9.8 to -3.2) with HRI treatment and -0.38±1.3% (95% CI -0.70 to -0.05); -4.2±14.2 mmol/mol (95% CI -7.7 to -0.5) with RAI treatment, with ETD of -0.22% (95% CI -0.67 to 0.22); -2.4 mmol/mol (95% CI -7.3 to 2.4), p=0.007, confirming non-inferiority of HRI to RAI. No between-group differences in changes in total daily insulin doses, number of hypoglycemic values (≤70 mg/dL (≤39 mmol/L) or body weight were observed. No severe hypoglycemic events were reported. Direct pharmacy cost savings (-US$265.85; 95% CI -US$288.60 to -US$243.11; p<0.0001) were observed with HRI treatment. CONCLUSIONS: Individuals with type 2 diabetes requiring insulin can be treated with V-Go wearable insulin delivery device using HRI, safely and effectively, and potentially at a much lower cost compared with RAI, which can lead to improved access to insulin therapy for these individuals. TRIAL REGISTRATION NUMBER: NCT03495908.

A Review of the Efficacy and Tolerability of Bempedoic Acid in the Treatment of Hypercholesterolemia.

Despite the widespread use of statins and ezetimibe to decrease low-density lipoprotein cholesterol (LDL-C) levels and associated atherosclerotic cardiovascular disease (ASCVD), many patients do not achieve adequate LDL-C lowering as per the recommended American College of Cardiology (ACC)/American Heart Association (AHA) and European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines and demonstrate residual cardiovascular risk. The introduction of proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors in 2015 was a promising addition to hypercholesterolemia therapies, but their cost and subcutaneous administration has limited their use, and therefore, new affordable and patient friendly treatment strategies are crucial to help reduce ASCVD risk. Bempedoic acid, a drug currently under investigation, is a small molecule that has been shown to upregulate LDL receptors, decrease LDL-C, and reduce atherosclerotic plaque formation in hypercholesterolemic patients. Furthermore, bempedoic acid is a prodrug that becomes activated by an enzyme expressed primarily in the liver, allowing it to avoid the potential myotoxicity associated with statin therapy. The purpose of this review is to summarize the major clinical studies evaluating bempedoic acid and describe its potential addition to currently approved lipid-lowering therapies.

Sodium-Glucose Cotransporter-2 (SGLT-2) Inhibitors for Cardiovascular Disease Prevention.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Because of these associated risks, managing diabetes and CVD, including heart failure (HF), has become a joint effort to reduce the risk of adverse outcomes. Although many patients with T2DM are receiving preventive therapies for CVD, their residual risk remains high for atherosclerotic CVD (ASCVD). Recent data regarding the use of antidiabetic medications to prevent negative cardiovascular outcomes has revealed a positive association with reduced major adverse cardiovascular events (MACE). One class of medications, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, are at the forefront of the cardiovascular outcomes prevention discussion. The clinical data presented in this review indicate the potential cardiovascular benefits of SGLT-2 inhibitors in patients with CVD and its potential value as a treatment option in preventing CVD in various patient populations.

A spotlight on alirocumab in high cardiovascular risk patients with type 2 diabetes and mixed dyslipidemia: a review on the emerging data.

Diabetes is a significant and independent risk factor for atherosclerotic cardiovascular disease (ASCVD), leading to morbidity and mortality among this population. The prevention of macrovascular complications, such as CVD, peripheral arterial disease, and cerebrovascular accident, in patients with diabetes is obtained through multifactorial risk reduction, including mixed dyslipidemia management and adequate glycemic control. For patients with diabetes, it is crucial to initiate adequate dyslipidemia therapy to achieve recommended low-density lipoprotein cholesterol (LDL-C) goal of <70 mg/dL or target non-high-density lipoprotein goal of <100 mg/dL. Lipid-lowering therapies (LLTs), such as statins and ezetimibe, are the cornerstone for plasma LDL-C lowering; however, individuals with diabetes are often unable to achieve target lipid goals with these therapies alone and frequently require additional treatments. A new class of LLTs, proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, provides a novel approach to lowering lipids in persons with high CV risk, such as those with diabetes. The clinical data presented in this review indicate the potential benefits of alirocumab in patients with diabetes and its value as a treatment option in patients with diabetic dyslipidemia with no significant safety concerns.