Daily Cardiology Research Analysis

BACKGROUND: Cholesteryl ester transfer protein (CETP) inhibition reduces low density lipoprotein-cholesterol (LDL-C) while simultaneously increasing high density lipoprotein-cholesterol (HDL-C) levels and improving HDL-particle functionality. These lipoprotein modifications may provide a novel pathway for Alzheimer disease (AD) prevention through effects on lipid modulation, antioxidant activity, and neuro-inflammation. This approach could prove particularly beneficial for APOE4 carriers, who face elevated risks for both AD and atherosclerotic cardiovascular disease (ASCVD). OBJECTIVES: To examine the effects of obicetrapib, an oral CETP inhibitor, on biomarker changes indicative of AD pathology among patients with ASCVD DESIGN: This was a pre-specified substudy of the BROADWAY trial, a phase 3, double-blind, placebo-controlled pivotal registration trial to evaluate the LDL-C lowering efficacy of obicetrapib in adult patients with established ASCVD and/or heterozygous familial hypercholesterolemia (HeFH), whose LDL-C was not adequately controlled, despite being on maximally tolerated lipid-lowering therapy. SETTING: The trial was conducted across 188 sites in China, Europe, Japan, and the United States. Participants were recruited from cardiology clinics and lipid specialty centers from 2021 to 2024. PARTICIPANTS: Participants with ASCVD in BROADWAY who had known ApoE status and phosphorylated tau-217 (p-tau217) measured at baseline and 12 months. INTERVENTION: Participants in BROADWAY were randomized 2:1 to receive oral obicetrapib 10 mg daily or placebo for 12 months. MEASUREMENTS: AD plasma biomarkers were measured at baseline and 12 months using standardized SIMOA assays. The key outcome measure of interest was change in plasma p-tau217 from baseline to 12 months. Other outcome measures included changes in p-tau217/(Aβ42:40), p-tau181, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL). RESULTS: The analysis population consisted of 1535 (61 %) of the 2530 BROADWAY participants. Median age was 67 years and 67.0 % were male. Baseline p-tau217 levels varied significantly by ApoE subgroups, with ApoE4 carriers generally having higher concentrations and ApoE4/E4 participants exhibiting the highest median concentration (0.56 pg/mL). Obicetrapib significantly attenuated p-tau217 increases compared to placebo (adjusted mean 2.09 % vs 4.94 %; P = 0.025). Treatment differences were most pronounced in ApoE4 carriers, where adjusted mean increases were 1.92 % and 6.91 %, for obicetrapib and placebo, respectively (P = 0.041). Furthermore, among ApoE4/E4 participants, there was a 7.81 % adjusted mean decrease in p-tau217 with obicetrapib compared to a 12.67 % increase with placebo, representing a 20.48 % treatment difference (P = 0.010). Positive trends were observed across secondary biomarkers, with obicetrapib also significantly limiting increases in the p-tau217/Aβ42:40 ratio compared to placebo (2.51 % vs 6.55 %; P = 0.004). In addition, among ApoE4/E4 participants, obicetrapib demonstrated significant effects on GFAP (-6.39 % vs +8.85 %; P = 0.006) and NfL (-10.49 % vs +6.82 %; P = 0.020). Strong correlations were observed between end-of-study obicetrapib plasma concentrations and biomarker improvements (r=-0.64), suggesting CETP inhibition as a potential mechanism, although other drug effects may also contribute to these changes. CONCLUSIONS: Obicetrapib significantly slowed AD biomarker progression over 12 months in participants with ASCVD, with the greatest effects in ApoE4 carriers. Among ApoE4/E4 participants, obicetrapib reduced p-tau217 levels by a placebo-adjusted 20.48 % and demonstrated consistent effects across multiple AD biomarkers. These findings represent the first demonstration of an oral intervention capable of reducing both beta-amyloid and tau pathology biomarkers in ApoE4 carriers, offering a potential preventive strategy for this high-risk population who currently have no effective prevention options. Future research will need to establish whether these biomarker changes translate to clinical benefits in dedicated AD prevention trials. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05142722.

BACKGROUND: Transcatheter aortic valve intervention (TAVI) has revolutionized the care of older adults with aortic stenosis. OBJECTIVES: The objectives of the study were to examine associations between chronic conditions and outcomes after TAVI and to describe palliative care utilization rates. METHODS: This cohort study used the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy registry to identify patients who underwent TAVI and were eligible for linkage with Centers for Medicare & Medicaid Services claims data. The exposure was multiple chronic conditions (MCCs) in the year before TAVI. Associations between chronic conditions and outcomes were assessed using multivariable logistic regression. RESULTS: A total of 188,629 TAVI procedures were linked to Centers for Medicare & Medicaid Services claims. The median (IQR) age was 82.0 (76.0-87.0) years; 86,841 (46%) were female. Chronic conditions were associated with worse 1-year mortality (high MCC [≥6 conditions] vs low MCC [<4 chronic conditions], adjusted HR: 2.33 [95% CI: 2.22-2.44]). Chronic conditions were associated with lower Kansas City Cardiomyopathy Questionnaire at baseline (high MCC median score 37.5 [21.4-56.8] vs low MCC median score 55.7 [37.5-75.0], P < 0.001); however, the average improvement in Kansas City Cardiomyopathy Questionnaire after TAVI was large and appeared independent of chronic disease burden (median score change high MCC 28.7 [9.9-48.4] vs low MCC 24.5 [8.3-42.2], standardized difference +13.8%). Palliative care encounters were rare (8,946, 4.7%) and varied significantly across centers (range 0% to 25% of cases). CONCLUSIONS: Chronic conditions are associated with worse survival after TAVI. However, most patients with high MCC are alive 1 year after treatment, and quality of life improvements appear independent of chronic disease burden. These data help clarify expected health gains for patients with chronic conditions and symptomatic aortic stenosis.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) remains a leading cause of cardiovascular mortality, yet significant gaps persist in understanding how contemporary management strategies influence long-term outcomes. AIM: We sought to provide novel insights into the characteristics, management variability, and 6-month outcomes of patients with OHCA admitted to eight intensive cardiovascular care units during a contemporary period. METHOD: This was a prospective multicentre registry of patients with OHCA admitted to intensive cardiovascular care units from October 2020 to December 2021. Patients were categorised by prognosis as either favourable outcome (Cerebral Performance Category [CPC] 1-2) or non-favourable outcome, including death (CPC 3-5). A multinomial logistic regression identified independent predictors of CPC 3-5. RESULTS: Among 288 patients, only 17.36% were women. Most arrests (88.93%) were witnessed, yet bystander cardiopulmonary resuscitation was initiated in just 69.18% of cases. Despite 80% of patients presenting with a shockable rhythm, an automated external defibrillator was used in only 58%. Median time to return of spontaneous circulation (ROSC) was 28 minutes. Marked variability in post-resuscitation care was observed across centres in the use of targeted temperature management, emergent coronary angiography, and multimodal neuroprognostication. At 6 months, 49% of patients exhibited CPC 1-2. Ninety-three per cent of discharged patients maintained a favourable neurological outcome, and 15% improved their CPC score. Independent predictors of CPC 3-5 included older age (p=0.005), male sex (p=0.016), previous stroke (p=0.046), prolonged time to ROSC (p<0.001), and a non-shockable initial rhythm (p<0.001). Hypoxic-ischaemic brain injury was the leading cause of in-hospital death (72.90%). CONCLUSIONS: Nearly half of the patients with OHCA survived with a favourable neurological outcome, which persisted after 6 months. Despite significant in-hospital interventions, pre-hospital factors remained the strongest predictors of neurological outcome. The high degree of management variability suggests an urgent need for standardised protocols and supports the creation of cardiac arrest centres.