Risk Of Adverse Events Research Articles

Perioperative administration of sub-anesthetic ketamine/esketamine for preventing postpartum depression symptoms: A trial sequential meta-analysis

Objective Postpartum depression (PPD) is a major mental health issue affecting 10%–15% of women globally. This meta-analysis synthesized updated evidence on sub-anesthetic ketamine/esketamine’s efficacy in preventing PPD. Methods Randomized controlled trials (RCTs) comparing ketamine/esketamine to a placebo for PPD prevention were searched without language restriction. Primary outcomes were PPD risk at 1- and 4–6-week postpartum. Secondary outcomes included the difference in depression scores and risk of adverse events. Trial sequential analysis (TSA) was conducted to validate the reliability. Results A meta-analysis of 22 RCTs (n = 3,463) showed that ketamine/esketamine significantly decreased PPD risk at 1- (risk ratio [RR], 0.41; 95% confidence interval [CI], 0.3–0.57) and 4–6-week (RR, 0.47; 95%CI, 0.35–0.63) follow-ups. Consistently, participants receiving ketamine/esketamine had lower depression-related scores at 1- (standardized mean difference [SMD], −0.94; 95%CI, −1.26 to −0.62) and 4–6-week (SMD, −0.89; 95%CI, −1.25 to −0.53) follow-ups. Despite potential publication bias, TSA confirmed the evidence’s reliability. Subgroup analysis showed that ketamine/esketamine’s preventive effect on 1-week PPD was consistent, regardless of administration timing, type of agents, or total dosage (<0.5 vs. ≥0.5 mg/kg). For the 4–6-week period, PPD risk was favorably reduced only with postoperative administration or the use of esketamine, with the total dosage having no observed influence. Participants on ketamine/esketamine experienced more frequency of hallucinations (RR, 4.77; 95%CI, 1.39–16.44) and dizziness (RR, 1.36; 95%CI, 1.02–1.81). Conclusion Our findings advocate for the postoperative administration of low-dose ketamine/esketamine to avert PPD, which needed additional research for confirmation.

The safety of indocyanine green in patients with advanced chronic kidney disease or kidney transplantation – a scoping review

Near-infrared fluorescence imaging with indocyanine green (ICG) is increasingly being used in the field of image-guided surgery. Although ICG is considered non-nephrotoxic in current literature, caution is advised for the use of ICG in patients with advanced chronic kidney disease (CKD), including kidney transplant recipients. Therefore, a scoping review was performed to assess the safety of ICG in patients with advanced CKD or a renal allograft. This scoping review was guided by the PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-analyses extension for Scoping Reviews). Web of Science, PubMed, and Embase were searched for articles and abstracts in which ICG was administered in patients with CKD or a renal allograft. The extracted data included the incidence of adverse events, kidney function after injection of ICG, preservation of transplant function, and type of other possible complications. The initial search resulted in 635 records of which nineteen studies were found eligible for the review. ICG was used for multiple purposes but never specifically as an objective to investigate possible nephrotoxicity. No adverse events were reported in the transplant group (n=250) or the CKD group (n= 74). Despite ICG-injection, preservation of transplant function after transplantation surgery was 94% in 198 patients, and no increase in possible ICG-related other complications was reported. This scoping review found no evidence that ICG increases the risk of adverse events in patients with CKD, including kidney transplant recipients. Therefore, the administration of ICG should not be withheld from these patients.

Treatment Preferences of Physicians Treating Adult Patients with Attention-Deficit/Hyperactivity Disorderin the United States and Canada: A Discrete Choice Experiment.

Factors influencing attention-deficit/hyperactivity disorder (ADHD) treatment preferences have been studied among patients but not physicians in the United States (US) and Canada. This study assessed treatment preferences of physicians treating adult patients with ADHD in both countries. An online discrete choice experiment (DCE) was conducted (October 4-20, 2023) among physicians from Dynata's US and Canadian panel who treated adult patients with ADHD. Preference weights for efficacy (improvement in ADHD symptoms) and safety [risks of adverse events (AEs)] attributes were estimated using a conditional logistic regression model, and were used to calculate the willingness to trade-off and relative importance of the attributes. Among 510 US and 347 Canadian physicians (64.1% and 69.2% male, respectively), improvement in ADHD symptoms had a significant positive impact, and the risks of AEs (except the risk of feeling jittery in Canada) had a significant negative impact on physician preferences for ADHD treatments. US physicians were willing to tradeoff 0.44, 0.35, 0.20, 0.17, and 0.17 percentage points of improvement in ADHD symptoms to avoid a one-percentage-point risk of insomnia, nausea, feeling jittery, anxiety, and dry mouth, respectively; among Canadian physicians, these were 0.31, 0.21, 0.12, 0.20, and 0.07, respectively. The relative importance of the efficacy versus safety attributes (i.e., the risks of AEs included in the DCE taken together) was 45.5% versus 54.5% in the US and 56.3% versus 43.7% in Canada. Efficacy was the most important single attribute for physicians treating adult patients with ADHD in both the US and Canada; however, the risks of AEs taken together had greater relative importance than efficacy alone among US but not Canadian physicians. These findings highlight potential discrepancies in physician and patient preferences based on existing evidence and underscore the importance of shared decision-making, which may in turn increase patients' treatment satisfaction.

Artificial intelligence, medications, pharmacogenomics, and ethics.

Artificial Intelligence (AI) and Machine Learning (ML) are revolutionizing various scientific and clinical disciplines including pharmacogenomics (PGx) by enabling the analysis of complex datasets and the development of predictive models. The integration of AI and ML with PGx has the potential to provide more precise, data-driven insights into new drug targets, drug efficacy, drug selection, and risk of adverse events. While significant effort to develop and validate these tools remain, ongoing advancements in AI technologies, coupled with improvements in data quality and depth is anticipated to drive the transition of these tools into clinical practice and delivery of individualized treatments and improved patient outcomes. The successful development and integration of AI-assisted PGx tools will require careful consideration of ethical, legal, and social issues (ELSI) in research and clinical practice. This paper explores the intersection of PGx with AI, highlighting current research and potential clinical applications, and ELSI including privacy, oversight, patient and provider knowledge and acceptance, and the impact on patient-provider relationship and new roles.

Radiotherapy in patients with brain metastases with and without concomitant immunotherapy: comparison of patient outcome and neurotoxicity.

Recently, immune checkpoint inhibitors (ICI) have been added to the treatment of brain metastases. While combining radiotherapy and ICI can enhance therapeutic effects, it might also increase the risk of severe autoimmune adverse events. This retrospective study aims to compare treatment responses and neurotoxicity in patients treated with radiotherapy alone versus those receiving a combination of radiotherapy and ICI. All patients with brain metastases who received radiotherapy at Hannover Medical School from 2017 to 2019 were included. The medical reports of all study participants were evaluated. Patients who received radiotherapy alone and those who received a combination of radiation and ICI were compared. A total of 248 patients were analyzed, with the most common tumor types being non-small cell lung cancer (NSCLC) and malignant melanoma. Half of the patients received whole-brain radiotherapy (WBRT) and the other half stereotactic radiotherapy (SRT). Of these, 29 patients received concurrent immunotherapy and radiotherapy, 30 completed immunotherapy before radiotherapy, and 29 started ICI after completing radiotherapy. Two cases lacked information on the duration of immunotherapy. Overall survival post-initial tumor diagnosis within the total cohort was 52months, with significantly worse survival for patients with multiple brain metastases (p = 0.020). No significant differences in survival or incidence of neurological adverse events were observed between patients with or without ICI. Combining radiotherapy and ICI did not significantly increase neurotoxicity or improve survival in this cohort, though the heterogeneity of the subgroups limits the generalizability of these findings.

Updated evidence on cardiovascular and renal effects of GLP-1 receptor agonists and combination therapy with SGLT2 inhibitors and finerenone: a narrative review and perspectives.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have a reliable hypoglycaemic and weight-loss effect that can intervene in obesity, which is the basis of type 2 diabetes pathology. GLP-1RA therapy has shown potential benefits in reducing the risk of major adverse cardiovascular events and improving kidney outcomes in patients with diabetes at high risk for cardiovascular disease. More recent evidence is expanding their benefits to heart failure with preserved ejection fraction and clinically important renal outcomes in patients with and without diabetes. Some sub-analyses of large clinical trials suggest that GLP-1RA and sodium-glucose cotransporter 2 inhibitor combination therapy may provide more significant reductions in heart failure hospitalization and renal composite events than each alone. Moreover, the addition of finerenone to this combination therapy could potentially provide stronger cardiorenal protective benefits. Further studies are needed to assess the potential cardiovascular and renal benefits of combination therapy and to determine suitable patient population for the therapy.

Adverse events after nivolumab and ipilimumab combined immunotherapy in advanced renal cell carcinoma: a multicentre experience in Poland.

Immune checkpoint inhibitors (ICIs) have been employed in the adjuvant and metastatic setting of renal cell carcinoma (RCC) treatment. Among ICIs, combined immunotherapy has the highest risk for immune-related adverse events (irAEs). We aimed to document the incidence of irAEs in RCC patients treated with nivolumab and ipilimumab as data from the European population remain limited. We analysed data from 88 RCC patients treated with nivolumab + ipilimumab between May 2022 and June 2024 across six high-volume oncology units in Poland. We reviewed irAEs and estimated their impact on survival parameters via univariate and multivariate Cox proportional hazards regression models, along with log-rank tests. With a median follow-up of 11.3 months, the median overall survival (OS) was not reached, whereas the median progression-free survival (PFS) was 12.8 months (6.3-19.3). A total of 74 irAEs were recorded in 50 patients. The most frequent events were endocrine (n = 20, 27%), hepatic (n = 15, 17%), general (n = 12, 13.6%), and cutaneous (n = 11, 12.5%). The occurrence of irAEs was associated with a 60% lower risk of disease progression (hazard ratio 0.44, 95% confidence interval 0.2-0.87, p = 0.018) without impacting OS and higher disease control rate (n = 45, 90% vs. n = 24, 63.2%, p = 0.004). In contrast, patients with hepatotoxicity had poorer outcomes, with a 2.6-fold greater risk of death (p = 0.05). IrAEs may serve as a predictive factor for the efficacy of the nivolumab + ipilimumab regimen in RCC patients. Special attention is needed for hepatotoxicity, as it can significantly impact survival outcomes.

Efficacy and safety of rituximab in patients with lupus nephritis: A systematic review and meta-analysis.

Our aim was to systematically evaluate the efficacy and safety of rituximab (RTX) in patients with lupus nephritis (LN). PubMed, Embase, China National Knowledge Infrastructure (CNKI), Cochrane Library, and Wanfang Databases were searched to collect literature on the efficacy and safety of RTX in patients with LN. Odds ratios (ORs), weighted mean differences (WMDs), and standardized mean differences (SMDs) were used to represent treatment efficacy and overall outcome. The outcomes included complete renal remission rate, proteinuria, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, serum creatinine, any adverse events and serious adverse events. We explored the heterogeneity with I2 and assessed publication bias with funnel plot and Egger's test. Nine studies involving 723 patients (254 in the RTX group and 469 in the control group) were included in our systematic review and meta-analysis. RTX resulted in a higher complete renal remission rate (OR: 2.62; 95% CI 1.43 - 4.79, p = 0.024, I2 = 54.7%) than the control group. It significantly decreased SLEDAI scores (WMD = -3.79, 95% CI: -5.78 to -1.8, p < 0.001, I2 = 94.7%) as well as proteinuria (WMD = -0.9, 95% CI: -1.6 to -0.2, p < 0.001, I2 = 97.6%). There were no significant differences in any adverse events and serious adverse events between the RTX group and control group. RTX was an effective therapeutic agent in patients with LN, and it did not increase the risk of adverse events compared to the control group.

TREATMENT OPTIONS FOR RECURRENT MALIGNANT DIFFUSE ASTROCYTOMA (WHO GRADE IV)

Objectives We present the case of a 37-year-old female who underwent partial resection in 2018 for a diffuse fibrillary astrocytoma (WHO II) that invaded almost the entire right cerebral hemisphere. The patient followed conventional radiotherapy and chemotherapy. She presents after 6 years of regularly follow-ups with left hemiparesis, intracranial hypertension syndrome and tumor recurrence on MRI. The patient underwent another surgical intervention and the new histopathological diagnosis was diffuse astrocytoma grade IV. Therapeutic options for these patients are limited considering the fact that a gross total resection or a conventional re-irradiation could impact the quality of life. Therefore, exploring new therapeutic methods, such as targeted molecular therapy like EGFR antagonists or proteasome inhibitors, or proton therapy, should be considered. Material and Methods We conducted extensive research in two public medical databases for information related to the molecular pathways and management of primary and recurrent malignant astrocytoma and relevant articles were selected. Subsequently, we correlated this information with our direct experience in our case and discussed the observed results. Results Treatment modalities for these patients include reintervention, re-irradiation and second line chemotherapeutics. In relapsing cases the goal of reintervention is both to alleviate symptoms and obtain tumoral tissue for immunohistochemical analysis for identification of the new mutations. Conventional re-irradiation for large lesions carries high risks of producing both short-term and long-term side effects, impacting the quality of life. Alternatively, proton therapy minimizes the risk of adverse events due to Bragg peak reducing the irradiation of the surrounding tissue. Conclusions Genetic characterization of these lesions can facilitate targeted molecular therapy and help in establishing the prognosis. Re-irradiation of malignant astrocytomas with proton therapy is an effective treatment measure allowing for comparable tumor control to conventional radiotherapy.

Real-world research on beta-blocker usage trends in China and safety exploration based on the FDA Adverse Event Reporting System (FAERS).

Beta-blockers are widely used, with continuously updated clinical recommendations. However, their application faces challenges in personalized treatment and safety. The study aimed to investigate the frequency and patterns of prescribing beta-blockers in China and to explore potential adverse event risk signals associated with beta-blockers, providing reference for rational medication use in clinical settings. Prescription data for beta-blockers from January 2018 to June 2023 were extracted through the Hospital Prescription Analysis Collaborative Project in China to analyze clinical usage trends. While adverse drug reaction reports for beta-blockers were obtained from the FDA Adverse Event Reporting System (FAERS) database. The classification and standardization of adverse drug event (ADE) reports were based on the preferred terms (PT) and corresponding system organ classes (SOC) from the Medical Dictionary for Regulatory Activities (MedDRA). Signal detection utilized a proportion imbalance method. In clinical practice, metoprolol dominated beta-blocker prescriptions in China, accounting for 62.2%. Beta-blockers were primarily prescribed to the elderly (65.7%) and male patients (57.0%). However, off-label use of beta-blockers was relatively widespread. For instance, sotalol was prescribed for hypertension at 18.25%, while esmolol was used for angina and heart failure at rates of 12.94% and 14.98%, respectively. In addition, we identified newly discovered adverse reactions associated with beta-blockers, such as BRASH syndrome (metoprolol: n = 186, ROR = 391.285; carvedilol: n = 72, ROR = 256.459), acute kidney injury (bisoprolol: n = 247, ROR = 5.641), premature baby (labetalol: n = 110, ROR = 91.385), and sleep disorder (propranolol: n = 254, ROR = 10.98). Metoprolol led the beta-blocker market in China. Attention was warranted regarding the newly discovered adverse reactions, such as the risk of acute kidney injury with bisoprolol and the potential for BRASH syndrome with metoprolol and carvedilol.

Association among major adverse cardiovascular events with immune checkpoint inhibitors: A systematic review and meta-analysis.

This meta-analysis aimed to determine the incidence and overall risk of major adverse cardiovascular events (MACEs) related to immune checkpoint inhibitors (ICIs). We systematically searched all cohort studies, including the available MACE data in cancer patients receiving ICIs, in PubMed, Embase, and the Cochrane Library, from their inception to September 5, 2023. The primary outcome was the incidence of MACEs associated with ICI exposure, and the secondary outcome was the overall risk of MACEs associated with ICI exposure versus non-ICI exposure controls. Risk ratios with 95% confidence intervals were used in the random- or fixed-effects models. Overall, 26 cohort studies met the inclusion criteria, involving 109,883 cancer patients. In the median follow-up period ranging from 3.3 to 55.2 months, the incidence of MACEs associated with ICI exposure was 8.22%, ranging from 0.55% to 3.98%, among the nine MACEs, including myocarditis, tachyarrhythmia, pericarditis, pericardial effusions, cardiovascular death, myocardial infarction, heart failure, stroke, and conduction disorder. The incidence of MACE associated with non-ICI exposure was 3.84%, ranging from 0.81% to 4.72%. The risks of all-grade MACEs and pericardial effusions were significantly higher in the ICI group than in the non-ICI controls. ICI treatment, age, male sex, and prior radiation therapy were significantly associated with MACEs. The risk of MACEs during ICI treatment in patients with cancer is more common than is currently recognized. ICI use is closely associated with an increased risk of MACEs. Patients at risk were older, male, and had a history of radiation therapy.

Translation and Adaptation of the STOPP/START Criteria Version 3 for Potentially Inappropriate Prescribing in Older People to European Portuguese: A Study Protocol.

As the global population ages, managing medication use in older adults becomes increasingly complex due to polypharmacy and the associated risks of adverse drug events. To improve the safety and appropriateness of medication use in the older population, tools like the Screening Tool of Older Persons' Prescriptions (STOPP) and Screening Tool to Alert doctors to Right Treatment (START) criteria have been developed. The availability of updated criteria is crucial to better support healthcare professionals in Portuguese-speaking regions. The aim of this study is to translate and validate the STOPP/START version 3 criteria for Portuguese, providing an updated and useful tool for healthcare professionals. This study will be conducted through four phases: I) translation of the STOPP/START version 3 criteria to European Portuguese; II) collection of sociodemographic, clinical, and medication data; III) intrarater reliability study; and IV) interrater agreement study. This study obtained ethics approval by the Ethics Committee of the Administração Regional de Saúde do Centro, Portugal. The availability of the translated criteria will enable the integration of STOPP/START version 3 into clinical practice in Portugal, facilitating improved medication safety and appropriateness. This integration is expected to lead to better management of polypharmacy and a reduction in adverse drug events, ultimately enhancing patient outcomes and supporting evidence-based prescribing practices.

Biologics and Oral Small Molecules Are Not Associated With Increased Major Adverse Cardiovascular Events or Venous Thromboembolism in Inflammatory Bowel Disease.

Biologics and oral small molecules (OSM) effectively treat inflammatory bowel disease (IBD), but some are linked to higher risks of major adverse cardiovascular events (MACE) and venous thromboembolism (VTE). This study evaluates the MACE and VTE risks in IBD patients treated with biologics or OSM. Using the TrinNetX multi-institutional database, we examined MACE and VTE in adult IBD patients on biologics and compared them to IBD patients not on biologics. We also compared IBD patients on OSM to those not on OSM. We performed 1:1 propensity score matching. MACE (myocardial infarction [MI], stroke, and all-cause mortality) and VTE were assessed from 30 days to 3 years after drug prescription. After matching, IBD patients on biologics had reduced risk of MI, stroke, and all-cause mortality at 1 year, compared to those not on biologics (P < .05). No significant difference in VTE was observed (P = .5). At 3 years, biologic-treated patients had lower risks of MI, stroke, all-cause mortality, and VTE (P < .05). Inflammatory bowel disease patients on OSM showed no significant differences in MI, stroke, or VTE at 1 and 3 years, but had lower all-cause mortality (P < .05). In older IBD patients with at least 1 cardiovascular risk factor, OSM usage showed no significant difference in MI, stroke, or VTE risk compared to nonusers; however, all-cause mortality was decreased at 3 years (P < .05). Inflammatory bowel disease patients treated with biologics or OSM were not at increased risk of MACE or VTE. Although further studies and longer follow-up periods are needed to confirm these findings, our results provide reassurance regarding the safety of these medications in IBD.

Sequential Grafting of the Left Internal Thoracic Artery to the Left Anterior Descending Artery and Graft Failure.

There is concern that left internal thoracic artery (LITA) to diagonal to left anterior descending artery (LAD) grafts may be more susceptible to failure compared to single LITA-LAD grafts. Pooled individual patient data from eight clinical trials with systematic graft imaging were analyzed to assess the incidence of sequential LITA-Diagonal-LAD vs. single LITA-LAD grafts. Mixed-effects multivariable logistic regression, adjusting for patient characteristics and clustering within trials, was used. Of 3969 patients with LITA-LAD grafts, 283 (7.1%) patients received sequential LITA-Diagonal-LAD grafts. Patients with sequential LITA-Diagonal-LAD grafts were older (66 vs. 65 y, p=0.009) and more often male (88% vs. 83%, p=0.03). Overall, graft failure occurred in 9.3% of patients with LITA-LAD grafts, with more graft failure occurring in single (9.5%) than in sequential LITA-Diagonal-LAD grafts (6.4%, p=0.08) at a median (25th-75th percentile) time to imaging of 1.0 (1.0-1.1) years. After multivariable adjustment, sequential LITA-Diagonal-LAD grafting was not associated with graft failure (adjusted odds ratio: 1.22, 95% confidence interval: 0.68-2.18, p=0.55). There was no difference in mortality (2.8% vs. 5.3%, p=0.06), myocardial infarction (1.4% vs. 1.6%, p=0.90), revascularization (4.5% vs. 7.3%, p=0.08), or stroke (1.7% vs. 1.2%, p=0.40) between groups. In selected patients, LITA-Diagonal-LAD grafting was not associated with higher risk of graft failure or adverse clinical events at one year.

Analysis of influential factors of stent-related adverse events after percutaneous coronary intervention more than twice: a single-center retrospective study.

We aimed to assess the factors affecting patient outcomes in multiple stent placements over a 10-year period. The single-center study included 1,200 patients who had multiple stents implanted at least twice or more. Participants were divided into the adverse outcomes as endpoints (n = 204 [17%]) and control groups. Univariate and multivariate analyses of stent-related adverse events risk during 10 years and logistic regression analysis of the adverse outcomes risk factors were performed. Univariate analysis revealed the impact of acute coronary syndrome (ACS), diabetes mellitus, hypertriglyceridemia, cumulative lesions in the left anterior descending (LAD) and left circumflex (LCX) arteries, number of stents in the LAD, LCX, and right coronary artery (RCA), presence of multiple coronary artery lesions, total number of stents used, and intervals between the first and second and between the fourth and fifth implantations. For secondary stent implantation, significant factors in univariate analysis included the number of LAD and LCX lesions, stents in LAD, LCX, and RCA, extent of coronary lesions, ACS, hypertension, diabetes, and total stent count. Many factors affect the outcomes in this patient group over time. Reducing the need for frequent percutaneous coronary intervention and considering the number of stents implanted are essential to improving outcomes.

Abstract 4143281: The Influence of Personal and Family Support on Maternal Cardiovascular Health: Insights from a TriNetX Study

Background: Maternal cardiovascular health during and after pregnancy is influenced by various factors, including personal and family support. However, the specific impact of abnormal personal and family support on maternal outcomes remains understudied. Methods: Utilizing the TriNetX global health research network within the US Collaborative Network, we investigated the influence of abnormal personal and family support (ICD10CM:Z63) on maternal cardiovascular outcomes within one year post-pregnancy. Cohort 1 comprised women aged 15 to 60 with documented problems relating to primary and family support during or after childbirth between 2008 and 2023. Cohort 2 included a similar demographic with good primary and family support. Data were extracted from electronic health records, and the cohorts were matched based on diverse sociodemographic traits and medical comorbidities. Results: Our analysis revealed significant associations between problems relating to primary and family support during and after pregnancy and adverse maternal cardiovascular outcomes. Specifically, the presence of such challenges significantly increased the risk of major adverse cardiac and cerebrovascular events (MACCE) (OR: 4.823, 95% CI: 3.361 to 6.919, p&lt;0.001) and all-cause mortality (OR: 8.461, 95% CI: 5.184 to 13.812, p&lt;0.001). Interestingly, it was associated with a reduced risk of peripartum or postpartum preeclampsia (OR: 0.603, 95% CI: 0.403 to 0.903, p&lt;0.001). However, no significant association was observed between these personal and family support challenges and acute MI (OR: 1.092, 95% CI: 0.482 to 2.747, p=NS), ischemic stroke (OR: 1.403, 95% CI: 0.623 to 3.160, p=NS), hemorrhagic stroke (OR: 1.000, 95% CI: 0.416 to 2.404, p=NS), heart failure (OR: 1.075, 95% CI: 0.636 to 1.817, p=NS), or peripartum cardiomyopathy (OR: 0.586, 95% CI: 0.322 to 1.068, p=NS). Conclusion: Our findings highlight the significant impact of abnormal personal and family support on maternal cardiovascular health outcomes during and one year after pregnancy. Addressing challenges related to primary and family support during and after pregnancy may be crucial for reducing adverse outcomes and enhancing overall maternal well-being.

Abstract 4136463: Novel Systemic Inflammatory Biomarkers Can Predict Significant Coronary Disease in High Risk Patients

Background: Coronary artery disease (CAD) is a major cause of morbidity and mortality worldwide. Chronic inflammation is a known risk factor for atherosclerosis, plaque formation, disease progression, and plaque instability. Novel inflammatory biomarkers have been recently linked to excess risk of adverse cardiovascular events, including incident myocardial infarction. Elevated inflammatory biomarkers may help identify patients at higher risk for severe CAD. Aim: This study aimed to evaluate the use of novel systemic inflammatory markers in predicting the pretest probability of severe CAD in patients referred to diagnostic coronary angiography in a single tertiary care center. Methods: This was a prospective observational cohort study enrolling consecutive patients referred to diagnostic coronary angiography in a tertiary care center. Preprocedural laboratory results were obtained from medical charts, including complete blood counts with differentials. Three novel systemic inflammatory markers were computed using existing mathematical formulas: systemic immune-inflammation index (SII = neutrophil count*platelet/lymphocyte); systemic inflammation response index (SIRI = neutrophil*monocyte/lymphocyte); and systemic immune inflammatory response index (SIIRI = neutrophil*monocyte*platelet/lymphocyte). The primary study outcome was severe CAD defined as the presence of ≥70% stenosis in one of three main coronary arteries requiring percutaneous coronary intervention). The outcome was adjudicated by an independent reviewers blinded to computations of biomarkers. Result: The sample included 264 patients (age 59.3±10.8, 47% Females). Overall, 84 patients (32%) met the primary study outcomes. In univariate analysis, those with severe CAD had significantly higher SIRI (2.9±0.7 vs. 2.6±0.6, p = 0.001) and SIIRI (8.4±0.8 vs. 8.1±0.7, p = 0.015) compared to their counterparts. In multivariate analysis adjusted for age and sex, only SIRI was an independent predictor of severe CAD. Using SIRI &gt; 20.8 (upper quartile) was associated with nearly three-fold excess risk of severe CAD (OR = 2.72, 95% CI 1.45-5.09). Conclusion: Elevated SIRI, a marker of ongoing systemic inflammatory response, could be indicative of severe CAD. As an inexpensive biomarker based exclusively on complete blood count, SIRI can be used to prioritize patients referred for diagnostic angiography and potentially expedite treatments in those at higher risk for coronary events.

Abstract 4120898: Assessment of Subclinical Atherosclerosis in Psoriasis Patients Using Echocardiographic Coronary Flow Parameters: A Systematic Review and Meta-Analysis

Background: Chronic inflammatory diseases are associated with a higher risk for atherosclerosis and adverse cardiovascular events. Psoriasis is a systemic inflammatory condition that significantly increases coronary artery disease risk. Subclinical atherosclerosis can be estimated by echocardiographic parameters like coronary flow velocity reserve (CFVR), diastolic peak flow velocity (DPFV), and hyperemic DPFV. Limited literature investigates these parameters in psoriasis, with inconsistent results. Methods: We systematically searched the major bibliographic databases including PubMed, Embase, Cochrane Library, and Google Scholar from inception to 7th May 2024 to retrieve relevant studies. The outcomes were pooled using the inverse variance random-effects model, and the results were presented as standardized mean difference (SMD) with the corresponding 95% confidence interval (CI). Results: 4 studies with 557 participants (281: psoriasis and 276: controls) were included. The mean age of the psoriasis group was 44.7 ± 7.7 years and of the control group was 45.2 ± 5.9 years. Psoriasis patients had a significantly lower CFVR [SMD: -0.71; 95% CI: -0.97, -0.45; p&lt;0.00001] and hyperemic DPFV [SMD: -0.71; 95% CI: -1.30, -0.12; p=0.02] compared to healthy controls. However, the difference between baseline DPFV was insignificant between the two groups [SMD: 0.20; 95% CI: -0.92, 1.32; p=0.73]. Conclusion: This study demonstrates that psoriasis is associated with coronary microvascular disease as measured by significantly lower CFVR and hyperemic DPFV. These results suggest that impaired myocardial perfusion in psoriasis patients may be an early manifestation of cardiac involvement. Hence, early risk stratification in psoriasis patients is crucial. Further large, randomized trials are essential to corroborate the results of this meta-analysis.

Abstract 4139186: Bempedoic Acid and Limb Outcomes in Statin-Intolerant Patients with Peripheral Artery Disease

Introduction: Patients with peripheral artery disease (PAD) are at high risk of major adverse limb events (MALE) and CV events and have high rates of recurrence of these events. Recently, bempedoic acid was shown to reduce MACE in primary and secondary prevention patients. Whether bempedoic acid reduces the risk of MALE is unknown. Methods: CLEAR Outcomes randomized 13,970 patients to bempedoic acid 180 mg or placebo. A clinical history of PAD was reported by investigators at baseline. Two blinded vascular medicine specialists independently adjudicated all adverse events for limb outcomes including worsening PAD symptoms leading to revascularization, chronic limb threatening ischemia, and acute limb ischemia events with the composite defined as MALE. Outcomes were assessed as time to first event as well as total (including recurrent) events using a negative binomial approach. Results: A total of 1,624 of the enrolled patients had PAD at baseline. Over a median of 41.1 months the rate of first and total MALE events in patients with PAD in the placebo group were 8.3% and 13.7% respectively. Bempedoic acid reduced first MALE events by 36% (HR 0.64, 95% CI 0.44-0.93) with an absolute risk reduction (ARR) of 2.5% and number needed to treat (NNT) of 40, compared to placebo (figure, panel A). Similarly, when considering total events, bempedoic acid reduced MALE by 45% (RR 0.55, 95% CI 0.35 – 0.85, figure panel b). Consistent benefits were observed for MALE in the overall population as well as composites of MACE and MALE in both populations (Figure panel b). There was no evidence of effect modification for the benefit of bempedoic acid for MALE on the basis of PAD at baseline (p-interaction 0.09). Conclusions: Bempedoic acid significantly reduces MALE. Benefits appear potentially greater when considering total (i.e. recurrent) events. These findings support the importance of LDL-C lowering therapy in patients with PAD. In addition, these findings support the early use of therapies with proven MALE benefit, including bempedoic acid, to optimize outcomes in PAD.

Abstract 4137243: Dynamic changes of pericoronary fat attenuation index predicting changes of coronary plaque burden

Background: Percent atheroma volume (PAV) is a validated index of coronary plaque burden, linking to adverse cardiac events. Meanwhile, pericoronary fat attenuation index (FAI) on coronary computed tomography angiography (CCTA) image is a novel prognostic marker of coronary inflammation. Research Questions: It is unknown the impact of coronary inflammation (i.e., FAI) on the progression of coronary PAV in patients at an increased risk of adverse cardiac events. Methods: Patients with type 2 diabetes mellitus (T2DM) who underwent at least two clinically indicated CCTA examinations (time interval &gt; 1 year) at our center were potentially eligible for enrollment. Eligible patients presented with more than one study plaque, defined as non-obstructive stenosis at baseline and not being intervened during serial CCTA. Longitudinal CCTA images were assessed for FAI and compositional plaque characteristics (e.g., PAV) using dedicated post-processing softwares. The relationships between changes in FAI and progression of compositional PAV were examined using the logistic and linear regression analysis. Results: A total of 204 T2DM patients (mean age, 61.2 ± 9.3 years; male, 68.1%) with 366 study plaques were enrolled. All patients were treated with statins, and their time interval between longitudinal CCTAs was 14.1 (12.9, 17.6) months. Compared with patients with improved coronary inflammation (ΔFAI ≤ 0), those with deteriorated coronary inflammation (ΔFAI &gt; 0) had lower high density lipoprotein cholesterol and baseline FAI, whereas higher blood pressure (all p &lt; 0.05). Meanwhile, compared to patients with ΔFAI ≤ 0, those with ΔFAI &gt; 0 had more Δoverall and Δnon-calcified PAV (all p &lt; 0.05). Importantly, these findings were consistent in a dedicated propensity score matching analysis. In logistic regression analysis, ΔFAI &gt; 0 was associated with annual progression of overall PAV and non-calcified PAV, whereas ΔFAI ≤ 0 associated with annual regression of overall PAV and non-calcified PAV after adjusting for cardiac risk factors, baseline PAV and medications (all p &lt; 0.05). Similarly, in linear regression analysis, changes of FAI were independently positively associated with annual changes of overall PAV (β=0.545, p&lt; 0.001) and non-calcified PAV (β=0.461, p&lt; 0.001) (Figure 1). Conclusion: In this longitudinal CCTA study, changes of coronary inflammation are closely correlated with changes of overall and non-calcified PAV among T2DM patients treated with statins.