Sodium-glucose cotransporter 2 (SGLT2) inhibitors have evolved from glucose-lowering agents into foundational therapies across the cardiovascular-kidney-metabolic (CKM) continuum. Large cardiovascular and renal outcome trials have consistently demonstrated reductions in heart failure (HF) hospitalization among patients both with and without diabetes and across the full spectrum of left ventricular ejection fraction, thereby transforming the management of established HF. Increasing attention has focused on whether SGLT2 inhibition may also influence upstream mechanisms implicated in the pathophysiology of HF with preserved ejection fraction (HFpEF) and potentially modify the trajectory toward its clinical onset. HFpEF arises from complex interactions among metabolic dysfunction, renal impairment, systemic inflammation, endothelial dysfunction, ventricular-arterial stiffening, and progressive atrial and ventricular remodeling within the CKM axis. SGLT2 inhibitors may influence several of these pathways through natriuresis and osmotic diuresis, improvement in ventricular loading conditions, attenuation of neurohormonal activation, enhancement of myocardial energetics, and anti-inflammatory and antifibrotic effects. Emerging mechanistic and imaging studies further suggest favorable effects on left atrial remodeling, diastolic reserve, pulmonary vascular load, and right ventricular–pulmonary arterial coupling. Although randomized trials specifically designed to evaluate primary prevention of HFpEF are lacking, consistent reductions in HF events across high-risk CKM populations support a potential disease-modifying role. This review integrates mechanistic and clinical evidence to examine how SGLT2 inhibition may alter the trajectory toward HFpEF and highlights priorities for future research.

Potent P2Y12 inhibition with prasugrel has become central to the management of acute coronary syndrome in patients undergoing percutaneous coronary intervention. Early large-scale randomized trials established standard-dose prasugrel-based 12-month dual antiplatelet therapy (DAPT) as an effective strategy for reducing ischemic events compared with clopidogrel, albeit at the cost of increased bleeding risk. Over the past two decades, accumulating pharmacokinetic, pharmacodynamic, and clinical evidence has reshaped the therapeutic landscape. Studies have demonstrated that older adults, patients with low body weight, and East Asian populations exhibit greater platelet inhibition and higher exposure to the active metabolite at lower prasugrel doses. These biological differences provide a rationale for reduced maintenance dosing strategies. Concurrently, advances in stent technology and improved understanding of temporal risk patterns have supported progressive shortening of DAPT duration. Contemporary studies have evaluated abbreviated DAPT followed by prasugrel monotherapy, as well as aspirin-withdrawal strategies aimed at minimizing bleeding without compromising ischemic protection. Although very early aspirin-free approaches have yielded mixed results, selected short DAPT strategies followed by reduced-dose prasugrel have demonstrated favorable net clinical outcomes. Taken together, the evolution of prasugrel-based therapy reflects a paradigm shift from uniform high-intensity treatment toward individualized modulation of antiplatelet intensity. Low-dose prasugrel should be regarded not as a therapeutic compromise, but as a calibrated strategy designed to optimize the balance between ischemic protection and bleeding risk.

Lipoprotein(a) (Lp(a)) represents a unique atherogenic lipoprotein that has emerged as an independent and causal risk factor for atherosclerotic cardiovascular disease. Unlike other lipoproteins, circulating Lp(a) concentrations are largely genetically determined and remain resistant to conventional lipid-lowering therapies. This review summarizes the current understanding of Lp(a) metabolism, its pathophysiological mechanisms, and emerging therapeutic approaches targeting this critical cardiovascular risk factor. Recent advances in Lp(a) research have clarified the complex interplay among genetic determinants, metabolic pathways, and downstream cardiovascular outcomes. Novel RNA-targeted therapies, including antisense oligonucleotides and small interfering RNAs, have demonstrated unprecedented reductions in Lp(a) levels of approximately 80% to 95% and are currently being evaluated in pivotal phase 3 cardiovascular outcome trials. The development of specific Lp(a)-lowering therapies represents a paradigm shift in cardiovascular prevention, offering renewed promise for the estimated 1.5 billion individuals worldwide with elevated Lp(a) levels. Ongoing outcome trials will ultimately determine whether targeted Lp(a) reduction translates into clinically meaningful cardiovascular benefit.

Obesity is a major global health issue and a leading contributor to cardiovascular disease (CVD). While traditional research has emphasized diet and physical inactivity, psychological factors, particularly emotional eating, are increasingly recognized as important contributors to metabolic and cardiovascular health. Emotional eating, defined as eating in response to negative emotions, represents a maladaptive coping mechanism that promotes excessive caloric intake, visceral fat accumulation, and metabolic dysregulation. Chronic stress activates the hypothalamic-pituitary-adrenal axis, leading to increased cortisol secretion and appetite, while recurrent emotional eating behaviors reinforce this biological pathway and contribute to insulin resistance, dyslipidemia, hypertension, and systemic inflammation. Together, these mechanisms link psychological stress to cardiometabolic dysfunction and ultimately to increased CVD risk. Although direct evidence linking emotional eating to clinical CVD outcomes remains limited, accumulating evidence supports its role as a behavioral mediator connecting psychological stress, metabolic abnormalities, and cardiovascular risk. Effective management of emotional eating requires an integrated approach that combines cognitive behavioral therapy, mindfulness-based strategies, stress management, healthy lifestyle modification, and pharmacological treatment for obesity when indicated. Recognizing emotional eating as a modifiable behavioral risk factor may open new opportunities for early prevention and holistic management of CVD.

Statins have revolutionized the management of dyslipidemia and remain the first-line therapy for preventing atherosclerotic cardiovascular disease. Despite these advantages, concerns regarding adverse effects, particularly muscle-related symptoms, hepatotoxicity, and new-onset diabetes mellitus, often hinder adherence and compromise cardiovascular protection. This review summarizes current evidence on statin-associated adverse effects and explores strategies to optimize their management. Statin-associated muscle symptoms (SAMS) are the most frequently reported side effects; however, randomized controlled trials demonstrate a low true pharmacologic incidence (<3%). The majority of SAMS are attributable to patient misperception or the nocebo effect. Proper evaluation, including measurement of creatine kinase, dose adjustment, and consideration of alternative lipid-lowering strategies such as ezetimibe or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, may allow patients to resume therapy. Statin therapy is also associated with a modest increase in new-onset diabetes, particularly at higher doses. However, the absolute risk is small and is outweighed by the substantial reduction in cardiovascular events. Hepatotoxicity related to statins is rare, generally mild, and reversible upon discontinuation. Clinically significant adverse effects of statins are uncommon, and most can be managed through careful patient assessment, objective diagnostic evaluation, and appropriate reassurance. Importantly, the cardiovascular benefits of statins far exceed their potential risks. Therefore, rather than avoiding statins because of concerns about side effects, clinicians should adopt evidence-based strategies to overcome these challenges and ensure safe, sustained cardiovascular protection.

The traditional definition of obesity, relying solely on body mass index, inadequately captures individual health status and is insufficient for guiding therapeutic interventions. In January 2025, The Lancet Diabetes & Endocrinology Commission proposed a paradigm-shifting redefinition that introduces the concepts of “clinical obesity” and “preclinical obesity.” Clinical obesity is defined as a chronic, systemic illness characterized by excess adiposity resulting in functional impairments in tissues, organs, or overall individual health. In contrast, preclinical obesity involves excess adiposity without current functional impairment. This review examines the significance of this new diagnostic paradigm for cardiovascular disease prevention and risk assessment. From a cardiovascular perspective, the new framework offers several advantages: it facilitates personalized intervention strategies based on individual risk profiles, refines cardiovascular risk assessments by incorporating body fat distribution and functional parameters, promotes more efficient resource allocation, and shifts treatment goals toward functional improvements beyond mere weight loss. Although further research is required to evaluate practical implementation and long-term outcomes, this novel approach represents a substantial advancement in obesity management and cardiovascular disease prevention.

Stroke is one of the major macrovascular complications of diabetes and increases morbidity and mortality. Hyperglycemia contributes to a heightened risk of stroke incidence. Moreover, people with diabetes may have poorer post-stroke outcomes and higher risk of stroke recurrence than those without diabetes. Recent cardiovascular outcome trials of some antidiabetic medications have shown beneficial effects on stroke prevention. Prevention and improving outcomes of stroke in patients with diabetes requires proper management of hyperglycemia and additional risk factors. This review is an evidence-based approach to epidemiology of stroke in diabetes, the role of glycemic control, and antidiabetic medications in stroke prevention in patients with diabetes mellitus.

Despite being the leading cause of mortality among women, cardiovascular disease remains underrecognized and undertreated due to sex-related differences in clinical presentation, risk factors, and healthcare delivery. Women are often excluded from clinical trials, undergo fewer diagnostic evaluations, and are less likely to receive guideline-directed therapies. Additionally, female-specific risk factors, such as pregnancy-related disorders, early menopause, and autoimmune diseases, are frequently overlooked. Addressing these disparities through sex-specific risk assessment, increased clinician awareness, and inclusion of women in research is imperative to optimize prevention and treatment strategies and reduce cardiovascular disease-related morbidity and mortality in women.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have transformed the treatment of both cardiovascular and renal diseases. Although originally developed for glycemic control in type 2 diabetes mellitus, these agents have demonstrated significant benefits by reducing cardiovascular events and slowing the progression of kidney disease, even in patients without diabetes. Landmark trials, including EMPA-REG OUTCOME, CANVAS, DECLARE-TIMI 58, and DAPA-HF, consistently demonstrated reductions in heart failure hospitalizations and renal deterioration among patients at high cardiovascular risk. However, many of these studies excluded patients with advanced chronic kidney disease (CKD), limiting the generalizability of their findings for this population. More recent investigations, such as CREDENCE, DAPA-CKD, and EMPA-KIDNEY, have focused on patients with CKD and confirmed that SGLT2 inhibitors offer significant renal and cardiovascular protection regardless of diabetic status. This review summarizes key clinical trials, outlining their design and outcomes with a particular emphasis on inclusion and exclusion criteria and the implications for CKD populations. Further, it discusses the practical application and safety considerations of SGLT2 inhibitors in nephrology, underscoring their emerging role as a fundamental therapeutic strategy in CKD management.

Direct oral anticoagulants (DOACs) have largely supplanted warfarin for stroke prevention in atrial fibrillation due to their superior safety and efficacy profiles. Although standard dosing regimens are well-established, lower doses—often referred to as ultra‐low-dose (ULD) DOACs—have been investigated in selected populations to balance thrombotic and bleeding risks. The concept of ULD DOACs was first introduced in the 2013 European Heart Rhythm Association Practical Guide specifically for post‐acute coronary syndrome patients with residual thrombotic risk. Clinical trials, including ATLAS ACS-TIMI 51 and COMPASS, demonstrated that rivaroxaban 2.5 mg twice a day reduced ischemic events when combined with aspirin, although this benefit was accompanied by an increased risk of major bleeding. Similarly, the ELDERCARE-AF trial revealed that edoxaban 15 mg once a day effectively prevented stroke in frail older patients. Conversely, evidence supporting ULDs of dabigatran and apixaban remains limited. Despite their potential benefits, inappropriate dose reductions based on subjective physician judgment rather than rigorous clinical guidelines may result in suboptimal anticoagulation and a heightened risk of thromboembolic events. This review explores the indications, supporting evidence, and potential risks associated with ULD DOACs, underscoring the need for well-designed studies to establish clear guidelines.