Factor XI/XIa inhibitors for the prevention and treatment of venous and arterial thromboembolism: A narrative review.

During the past decade, direct oral anticoagulants (DOACs) have advanced and simplified the prevention and treatment of venous thromboembolism (VTE). However, there remains a high incidence of bleeds, which calls for agents that have a reduced risk of bleeding. Factor XI (FXI) deficiency is associated with lower rates of venous thrombosis and stroke compared to the general population with a lower risk of bleeding. In conjunction with this, phase 2 studies have demonstrated safety and the potential for reduced thrombotic events with FXI inhibitors as compared to currently available medications. The aim of this review is to summarize key data on the clinical pharmacology of FXI, the latest developments in clinical trials of FXI inhibitors, and to describe the efficacy and safety profiles of FXI inhibitors for the prevention of venous and arterial thromboembolism.

Influenza vaccination in mitigating vascular events and risk.

PURPOSE OF REVIEW: Influenza imparts a significant health burden on the United States and global population. Furthermore, influenza is associated with acute cardiovascular events, including heart failure exacerbations, acute coronary syndromes, strokes, and overall cardiovascular mortality. We review the role of seasonal influenza vaccination in mitigating cardiovascular risk. RECENT FINDINGS: A large study assessed the impact of influenza vaccine on cardiovascular outcomes and mortality using the US National Inpatient Sample (NIS) database. This study included 22 634 643 hospitalizations. Vaccination against influenza was associated with a reduction in myocardial infarctions (MI) [relative risk (RR) = 0.84, 95% CI 0.82-0.87, P  < 0.001], transient ischemic attacks (RR = 0.93, 95% CI 0.9-0.96, P  < 0.001), cardiac arrests (RR = 0.36, 95% CI 0.33-0.39, P  < 0.001), strokes (RR = 0.94, 95% CI 0.91-0.97, P  < 0.001), and overall mortality (RR = 0.38, 95% CI 0.36-0.4, P  < 0.001). SUMMARY: Available data suggests that seasonal influenza vaccination is very effective in mitigating cardiovascular risk. Increasing the rates of influenza vaccination, especially among those with cardiovascular risk factors, is critical in preventing infection and attenuating influenza-related cardiovascular complications and adverse outcomes.

Sex Differences in Atrial Fibrillation.

PURPOSE OF REVIEW: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. The estimated lifetime risk of developing AF is higher in men; however, due to differences in life expectancy, the overall prevalence is higher among women, particularly in the older age group. Sex differences play an important role in the pathophysiology, presentation, and clinical outcomes of AF. Awareness of these differences minimizes the potential for disparities in AF management. Our review summarizes the current literature on sex differences in AF, including the epidemiology, pathophysiology, risk factors, clinical symptomatology, mechanisms, treatment, and outcomes. We also explore the implications of these differences for clinical practice and future research. RECENT FINDINGS: Women are more likely to present with atypical symptoms, have a higher stroke risk, and have a worse quality of life with AF when compared to men. Despite this, they are less likely to receive rhythm control strategies and anticoagulants. The sex-based differences in AF pathology and management might be a combination of inherent biological and hormonal differences, and implicit bias of the research entities and treating clinicians. Our review stresses the need for further sex-specific research in the pathophysiology of AF and opens a dialogue on personalized medicine, where management strategies can be tailored to individual patient characteristics, including sex.

Semaglutide for weight loss and cardiometabolic risk reduction in overweight/obesity.

PURPOSE OF REVIEW: Cardiovascular disease is the most common cause of morbidity and mortality worldwide, and the risk is heightened in the presence of obesity. We review semaglutide, a drug recently approved for chronic weight management in adults with obesity or who are overweight. RECENT FINDINGS: On 4 June 2021, the US Food and Drug Administration approved semaglutide injection at 2.4 mg once weekly for chronic weight management in adults with obesity or overweight with at least one weight-related condition such as high blood pressure, type 2 diabetes mellitus, or high cholesterol. This subcutaneous injection is the first approved drug for chronic weight management in adults with general obesity or overweight since 2014. The drug is indicated for weight management in patients with a BMI of 27 kg/m2 or greater who have at least one weight-related ailment or in patients with a BMI of 30 kg/m2 or greater. SUMMARY: Semaglutide offers adults with obesity or overweight a new treatment in conjunction with a weight management program consisting of reduced calorie diet and increased physical activity.

Current Use and Trends in Unprotected Left Main Coronary Artery Percutaneous Intervention.

PURPOSE OF REVIEW: To review the clinical evidence on the use of percutaneous coronary intervention (PCI) revascularization options in left main (LM) disease in comparison with coronary artery bypass graft (CABG). Coronary artery disease (CAD) involving the LM is associated with high morbidity and mortality. Though CABG remains the gold standard for complex CAD involving the LM artery, recent trials have shown a trend towards non-inferiority of the LM PCI when compared with CABG in certain subset of patients. RECENT FINDINGS: Two recent major randomized trials compared the outcomes of PCI versus CABG in the LM and multi-vessel disease with LM involvement. The NOBLE trial included patients with all range of Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) scores and utilized biolimus drug-eluting stent (DES). The trial concluded that MACCE (major adverse cardiac and cerebrovascular event) was significantly higher with PCI (28%) when compared with CABG (18%) but overall stroke and motility were not different. EXCEL trial evaluated the same treatment option in low to intermediate SYNTAX score population with third-generation everolimus DES platform as PCI option. Results showed no significant differences in the composite primary endpoints of death, stroke, and myocardial infarction (MI) at the end of 30 days (22% versus 19.2%, p = 0.13), although repeat revascularization was higher in PCI group (16.9% versus 10%). Recent evidence suggests that PCI is an acceptable alternative to treat symptomatic LM stenosis in select group of patients. In low to medium SYNTAX score, particularly in patients without diabetes mellitus, PCI remains a viable option. Future trials focusing on evaluating subset of patients who would benefit from one particular revascularization option in comparison with other is warranted.

An Overview of Arrhythmias in Pregnancy.

Cardiovascular disease significantly jeopardizes pregnancies in the United States, impacting 1% to 4% of pregnancies annually. Among complications, cardiac arrhythmias are prevalent, posing concerns for maternal and fetal health. The incidence of arrhythmias during pregnancy is rising, partly due to advances in congenital heart surgery and a growing population of women with structural heart disease. While most arrhythmias are benign, the increasing prevalence of more serious arrhythmias warrants a proactive approach. Guidance and reassurance suffice in many cases, but persistent symptoms require cautious use of antiarrhythmic drugs or other therapies for a safe outcome. Managing more serious arrhythmias requires a comprehensive, multidisciplinary approach involving specialists, including maternal-fetal medicine physicians, cardiologists, electrophysiologists, and anesthesiologists.

Comparative safety review of antithrombotic treatment options for patients with atrial fibrillation undergoing percutaneous coronary intervention.

INTRODUCTION: Balancing antithrombotic therapy for atrial fibrillation (AF) patients undergoing percutaneous coronary intervention (PCI) remains a clinical challenge due to coexisting thrombogenic risks. This review emphasizes the delicate balance required to prevent ischemic events while minimizing bleeding complications, particularly in the context of risk assessment. AREAS COVERED: This review spans from 2010 to October 2023, exploring the complexities of antithrombotic management for AF patients undergoing PCI. It stresses the need for personalized treatment decisions to optimize antithrombotic therapies effectively. EXPERT OPINION: The evolving evidence supports double antithrombotic therapy (DAT) over triple antithrombotic therapy (TAT) for these patients, showcasing a more favorable safety profile without compromising efficacy. Non-vitamin K antagonist oral anticoagulant (NOAC)-based DAT strategies exhibit superiority in reducing major bleeding events while effectively preventing ischemic events. Recommendations from the 2023 European Society of Cardiology (ESC) Guidelines advocate for NOAC-based DAT post-PCI, endorsing safer antithrombotic profiles.Challenges persist for specific patient categories requiring both oral anticoagulants and antiplatelets, necessitating personalized approaches. Future advances in intravascular imaging and novel coronary stent technologies offer promising avenues to optimize outcomes and influence antithrombotic strategies in AF-PCI patients.

Successful Treatment With the Oral Factor Xa Inhibitor Edoxaban in Heparin-Induced Thrombocytopenia With Thrombosis.

Heparin-induced thrombocytopenia with thrombosis (HITT) is a rare immune reaction to the drug heparin that causes increased blood clotting, putting patients at risk for arterial and venous thromboembolism which can have severe consequences. We present a case of HITT successfully treated with the direct oral anticoagulant (DOAC), edoxaban. A 56-year-old man had surgery to remove a colorectal mass. After discharge, he developed chest discomfort, shortness of breath, and low oxygen levels and was diagnosed with a right-sided lobar pulmonary embolism. His platelet count dropped, his tests confirmed a diagnosis of HITT, and he was initially treated with fondaparinux. After showing clinical and laboratory improvement, he was switched to edoxaban. Despite being diagnosed with colonic adenocarcinoma during follow-up, the patient's platelet count returned to normal, and he did not experience any more blood clots or serious bleeding events. The use of DOACs like edoxaban as potential therapies for HITT is promising; further research is being conducted to evaluate their effectiveness, safety, and potential benefits for treating this acquired high-risk thrombophilia.

The Use of Cardioprotective Devices and Strategies in Patients Undergoing Percutaneous Procedures and Cardiac Surgery.

In the United States, about one million people are seen to visit the operating theater for cardiac surgery annually. However, nearly half of these visits result in complications such as renal, neurological, and cardiac injury of varying degrees. Historically, many mechanisms and approaches have been explored in attempts to reduce injuries associated with cardiac surgery and percutaneous procedures. Devices such as cardioplegia, mechanical circulatory support, and other methods have shown promising results in managing and preventing life-threatening cardiac-surgery-related outcomes such as heart failure and cardiogenic shock. Comparably, cardioprotective devices such as TandemHeart, Impella family devices, and venoarterial extracorporeal membrane oxygenation (VA-ECMO) have also been proven to show significant cardioprotection through mechanical support. However, their use as interventional agents in the prevention of hemodynamic changes due to cardiac surgery or percutaneous interventions has been correlated with adverse effects. This can lead to a rebound increased risk of mortality in high-risk patients who undergo cardiac surgery. Further research is necessary to delineate and stratify patients into appropriate cardioprotective device groups. Furthermore, the use of one device over another in terms of efficacy remains controversial and further research is necessary to assess device potential in different settings. Clinical research is also needed regarding novel strategies and targets, such as transcutaneous vagus stimulation and supersaturated oxygen therapy, aimed at reducing mortality among high-risk cardiac surgery patients. This review explores the recent advances regarding the use of cardioprotective devices in patients undergoing percutaneous procedures and cardiac surgery.

The common pathobiology between coronary artery disease and calcific aortic stenosis: Evidence and clinical implications.

Calcific aortic valve stenosis (CAS), the most prevalent valvular disease worldwide, has been demonstrated to frequently occur in conjunction with coronary artery disease (CAD), the third leading cause of death worldwide. Atherosclerosis has been proven to be the main mechanism involved in CAS and CAD. Evidence also exists that obesity, diabetes, and metabolic syndrome (among others), along with specific genes involved in lipid metabolism, are important risk factors for CAS and CAD, leading to common pathological processes of atherosclerosis in both diseases. Therefore, it has been suggested that CAS could also be used as a marker of CAD. An understanding of the commonalities between the two conditions may improve therapeutic strategies for treating both CAD and CAS. This review explores the common pathogenesis and disparities between CAS and CAD, alongside their etiology. It also discusses clinical implications and provides evidence-based recommendations for the clinical management of both diseases.

Lipid Lowering Therapy: An Era Beyond Statins.

Dyslipidemia, specifically elevated low-density lipoprotein (LDL) cholesterol levels, causes atherosclerotic cardiovascular disease (ASCVD) and increases the risk of myocardial infarction and stroke. Statins, a class of drugs that exert their effects by inhibiting HMG-CoA reductase, a key enzyme in the synthesis of cholesterol, have been the mainstay of therapy for the primary prevention of cardiovascular disease and lipids reduction. Statins are associated with side effects, most commonly myopathy and myalgias, despite their proven efficacy. This review explores non-statin lipid-lowering therapies and examines recent advances and emerging research. Over the previous decades, several lipid-lowering therapies, both as monotherapy and adjuncts to statin therapy and lipid-targeting gene therapy, have emerged, thus redefining how we treat dyslipidemia. These drugs include Bile acids sequestrants, Fibrates, Nicotinic acid, Ezetimibe, Bempedoic acid, Volanesoren, Evinacumab, and the PCSK 9 Inhibitors Evolocumab and Alirocumab. Emerging gene-based therapy includes Small interfering RNAs, Antisense oligonucleotides, Adeno-associated virus vectors, CRISPR/Cas9 based therapeutics, and Non-coding RNA therapy. Of all these therapies, Bempedoic acid works most like statins by working through a similar pathway to decrease cholesterol levels. However, it is not associated with myopathy. Overall, although statins continue to be the gold standard, non-statin therapies are set to play an increasingly important role in managing dyslipidemia.