New Insights into the Potential of Obicetrapib, a Cholesteryl Ester Transfer Protein Inhibitor, to Reduce Vascular Contributions to Cognitive Impairment and Dementia
Alzheimer’s disease (AD) remains a leading cause of dementia worldwide, with complex pathophysiology involving amyloid deposition and tau pathology that precedes cognitive decline. Cardiovascular risk factors, including hypertension, type II diabetes, and dyslipidemia, are recognized as modifiable risk factors of AD, especially during midlife, underscoring the close interplay between AD and vascular contributions to cognitive impairment and dementia (VCID). Anti-amyloid immunotherapies offer potential for disease modification; however, they can transiently increase cerebral amyloid angiopathy (CAA), which may lead to serious and potentially fatal adverse effects known as amyloid-related imaging abnormalities (ARIA). These risks are particularly elevated in apolipoprotein E4 (APOE4) carriers, the major genetic risk factor for late-onset AD, underscoring the urgent need for improved safety measures and patient stratification strategies. Notably, the vascular pathways implicated in ARIA may overlap with mechanisms of amyloid clearance influenced by lipid metabolism. The objective of this study is to review how lipoproteins, including low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), influence amyloid clearance and vascular health, and discuss how cholesteryl ester transfer protein (CETP), a key regulator of lipoprotein exchange, has emerged as a potential therapeutic target in dementia. In addition to effectively lowering LDL-C and increasing HDL-C, the CETP inhibitor obicetrapib has recently shown promising results in slowing progression of a key AD biomarker, p-tau-217, over 12-month of treatment in patients with atherosclerotic cardiovascular disease, with more pronounced effects in APOE4 carriers. This minireview thus highlights the intersection of cardiovascular and neurodegenerative pathways and supports further exploration of lipid-modulating therapies in AD and VCID.
DOI: 10.29245/2578-3025/2025/3.1229 View / Download PdfCardiac Regeneration Innovation in the Clinical Trial Pipeline
Cardiovascular diseases remain the leading cause of mortality worldwide, with limited capacity for myocardial regeneration following injury. Regenerative strategies, including autologous and allogeneic cell-based therapies, gene therapy, and tissue constructs, are being investigated as potential approaches to restore cardiac function. We searched ClinicalTrials.gov on August 16, 2025, using the terms “heart regeneration”, restricting to interventional trials in phases 1-3. Trials unrelated to cardiac regeneration were excluded. Study characteristics were analyzed by condition, intervention type, phase, geographic distribution, sponsor, age group, and enrollment size. For completed studies, associated publications were reviewed to summarize efficacy and safety outcomes. Of 41 identified trials, 23 met inclusion criteria. Most were early-phase studies (11 phase 1, 9 phase 2, 3 phase 3). Myocardial infarction was the most common target (9 trials), followed by heart failure (8), coronary artery disease (5), and congenital heart disease (1). Autologous strategies predominated, though several allogeneic stem cell and gene therapy trials were also represented. The United States (6 trials) and Spain (5) were the leading contributors, followed by Germany (3), the Republic of Korea (3), and Poland (2). Enrollment ranged from 6 to 420 participants. Publications from completed trials demonstrated consistent safety but variable efficacy in improving left ventricular function and infarct size. Clinical research into cardiac regeneration remains dominated by small, early-phase, investigator-led studies, with limited large-scale, industry-driven development. While feasibility and safety have been established, efficacy signals remain inconsistent, underscoring the need for larger trials to clarify therapeutic benefit.
DOI: 10.29245/2578-3025/2025/3.1231 View / Download PdfSystemic Review of Current Strategies for Predicting Neurological Outcomes in Post-Cardiac Arrest Patients
Despite significant advances in cardiopulmonary resuscitation (CPR) and post-cardiac arrest care, out-of-hospital cardiac arrest (OHCA) remains a major public health problem, with high rates of death and severe long-term neurological impairment among survivors. This systematic review addresses the current methods in predicting poor neurological outcomes in comatose OHCA survivors, including both pre- and post hospital factors, neurophysiological tests, neurological exam, biomarkers, and neuroimaging. A multimodality, multidisciplinary approach incorporating these factors as well as the OCHA survivors and their surrogate decision makers’ values is proposed (WEMuV) to guide neuroprognostication and counseling. The review also identifies emerging technologies such as artificial intelligence and machine learning as promising innovations that could integrate and automate complex patient data analysis to provide more accurate, personalized risk assessments and improve outcomes in OHCA patients.
DOI: 10.29245/2578-3025/2025/3.1232 View / Download Pdf