Citations

Introduction: The safety and efficacy of direct oral anticoagulants (DOACs) compared to vitamin K antagonists (VKAs) remain unknown in patients with BMI ≥ 40 kg/m 2 . We aim to evaluate the risk of recurrent VTE and major bleeding in patients with a BMI ≥ 40 when started on DOACs versus VKAs. Methods: We conducted a systematic literature search according to PRISMA guidelines to identify studies using the terms: “venous thromboembolism”, “Vitamin K antagonists” and “direct oral anticoagulants”. After the screening, We extracted the data till May 2023 in a data extraction sheet. Our inclusion criteria were: adult patients, morbidly obese (BMI ≥ 40 kg/m 2 ), who were on DOACs or VKAs for VTE or atrial fibrillation. We used a variance-weighted random-effects model to analyze data on DOACs vs. VKAs, estimating event rates and odds ratios while assessing heterogeneity. Data were analyzed using the ‘meta’ package in R. Results: Our analysis included a total of 16 studies (n= 62704 patients). Obese patients on DOACs had a significant reduction in the risk of recurrent VTEs compared to VKAs OR 0.72 (95% CI: 0.59 - 0.88, I2 :19%). Also, DOACs were associated with a lower risk of major bleeding compared to VKAs in morbidly obese patients (OR = 0.65, 95% CI: 0.58 - 0.74, I2 :0%). For non-major bleeding, although the statistical significance was not reached, a consistent trend favoring DOACs was observed (OR = 0.76, 95% CI: 0.47-1.21). (Figure1) Conclusions: Among morbidly obese patients (BMI ≥ 40), DOACs are associated with a significantly lower risk of recurrent VTEs, and major bleeding compared to VKA. For non-major bleeding, there was a trend favoring DOACs over VKA. Increased recruitment of obese patients in clinical trials is needed to provide us with robust data for informed clinical decision-making.

Background: Depression is prevalent in almost half of patients with cardiovascular disease (CVD) and is associated with CVD and mortality. We used an artificial intelligence algorithm using ECG that predicts physiological age (ECG-Age) that has been linked to increased total and CVD mortality and CVD risk factors. We hypothesized that depressive symptoms would be associated with physiologic aging, as measured by AI-ECG Methods: A previously validated algorithm was applied to determine ECG-Age to 105,732 consecutive ECGs of individuals age ≥18 who sought care at Mayo Clinic between June 2019 and January 2022 and filled the Patient Health Questionnaire-9 (PHQ-9) within a month of ECG. PHQ-9 ascertains severity and frequency of depressive symptoms with values from 0 - 27 and were categorized as (None≤4, Mild 5-9, Moderate 10-14, Moderately severe 15-19 and Severe ≥20). Delta-Age was defined as ECG-Age minus chronological age and accelerated aging was defined as a Delta-Age >1SD above the mean. Logistic regression analyses associated PHQ-9 scores with positive Delta-Age while adjusting for CVD risk factors Results: Mean chronological age was 57±17 yr and mean ECG-Age 58±14 yr (R2 0.85, P < 0.0001), Delta-Age 0.71±9.40 yr, 58% women, average PHQ-9 5±6, 61% had none, 20% mild, 10 % moderate, 5%moderately severe and 4% had severe depressive symptoms. Delta-Age was 2.10 years higher in those with depressive symptoms, reflecting accelerated aging. Compared to those with no depressive symptoms, those with severe symptoms were 1.5 times more likely to have Delta-Age >1SD (OR 1.52 CI 95%1.73-1.33), independently of CV risk factors and the Charlson comorbidity index. Figure. There is significant attenuation of the association once accounting for age, sex and CVD risk factors Conclusions: Depressive symptoms are associated with physiologic aging, highlighting the role of depression in physiologic aging and the potential of preventive strategies in patients with depression and CVD

Abstract Purpose: The neutralizing peptibody trebananib prevents angiopoietin-1 and angiopoietin-2 from binding with Tie2 receptors, inhibiting angiogenesis and proliferation. Trebananib was combined with paclitaxel±trastuzumab in the I-SPY2 breast cancer trial. Patients and Methods: I-SPY2, a phase II neoadjuvant trial, adaptively randomizes patients with high-risk, early-stage breast cancer to one of several experimental therapies or control based on receptor subtypes as defined by hormone receptor (HR) and HER2 status and MammaPrint risk (MP1, MP2). The primary endpoint is pathologic complete response (pCR). A therapy “graduates” if/when it achieves 85% Bayesian probability of success in a phase III trial within a given subtype. Patients received weekly paclitaxel (plus trastuzumab if HER2-positive) without (control) or with weekly intravenous trebananib, followed by doxorubicin/cyclophosphamide and surgery. Pathway-specific biomarkers were assessed for response prediction. Results: There were 134 participants randomized to trebananib and 133 to control. Although trebananib did not graduate in any signature [phase III probabilities: Hazard ratio (HR)-negative (78%), HR-negative/HER2-positive (74%), HR-negative/HER2-negative (77%), and MP2 (79%)], it demonstrated high probability of superior pCR rates over control (92%–99%) among these subtypes. Trebananib improved 3-year event-free survival (HR 0.67), with no significant increase in adverse events. Activation levels of the Tie2 receptor and downstream signaling partners predicted trebananib response in HER2-positive disease; high expression of a CD8 T-cell gene signature predicted response in HR-negative/HER2-negative disease. Conclusions: The angiopoietin (Ang)/Tie2 axis inhibitor trebananib combined with standard neoadjuvant therapy increased estimated pCR rates across HR-negative and MP2 subtypes, with probabilities of superiority &gt;90%. Further study of Ang/Tie2 receptor axis inhibitors in validated, biomarker-predicted sensitive subtypes is warranted.