Risultati per: Short Acting Opioid

Circulation, Volume 150, Issue Suppl_1, Page A4139216-A4139216, November 12, 2024. Introduction:TX000045 (TX45) is a long-acting Fc-relaxin fusion protein with vasodilatory, anti-fibrotic and anti-inflammatory activity due to selective agonism of the G protein-coupled relaxin family peptide receptor 1 (RXFP1). It is being developed for Group 2 pulmonary hypertension associated with heart failure with preserved ejection fraction (HFpEF). This first-in-human study evaluated the safety/tolerability, pharmacokinetic and pharmacodynamic profile of TX45 in healthy volunteers after single doses.Methods:This phase 1a, randomized, double-blind, placebo-controlled single ascending dose study was performed in seven cohorts of healthy volunteers. Six cohorts consisted of eight patients receiving intravenously (IV) or subcutaneously (SC) one of several doses of TX45 (n=6 on treatment) or placebo (n=2), including 0.3 mg/kg IV, 1 mg/kg IV, 3 mg/kg IV, 150 mg SC (x2 cohorts), and 300 mg SC. One cohort consisted of seven patients receiving 600 mg SC TX45 (n=5 patients) or placebo (n=2 patients). The goals of the study were to assess the tolerability and safety, immunogenicity, pharmacokinetic (PK) and pharmacodynamic (PD = renal plasma flow, RPF) properties of TX45 in healthy volunteers after single doses. RPF was determined by analysis of steady-state para-aminohippurate (PAH) blood levels in response to a PAH IV infusion.Results:55 healthy volunteers were randomized. TX45 was well tolerated. Most adverse events were mild to moderate in intensity. The most common treatment emergent adverse event was transient orthostatic tachycardia, not associated with hypotension. TX45 demonstrated linear pharmacokinetics across the dose range with a terminal half-life estimated to be 13-23 days. Treatment with TX45, across dose levels, increased renal plasma flow by 16-42%, consistent with known relaxin effects. Leveraging repeated measures of renal plasma flow post dose, TX45 demonstrated prolonged maintenance of a pharmacodynamic effect. There was no evidence of immune mediated clearance of TX45.Conclusions:TX45 was generally well tolerated with a safety, pharmacokinetic and pharmacodynamic profile to support further clinical development. Its maximum effect on RPF is similar to previously described effects of native relaxin. Its half-life will support a prolonged dosing interval. These findings support further evaluation of TX45 in patients with Group 2 pulmonary hypertension associated with HFpEF.

Circulation, Volume 150, Issue Suppl_1, Page A4136013-A4136013, November 12, 2024. Introduction:The use of Transcatheter Aortic Valve Replacement(TAVR) has provided a safer alternative to open surgical approaches. The introduction of frailty scoring systems has proven effective in improving healthcare approaches and outcomes in various aspects of medicine. As there is a paucity of data on the impact of frailty among TAVR patients, we aim to conduct a retrospective study to investigate further.Methods:Our study analyzed adult cases with a primary procedural code for TAVR among hospitalizations between 2016 and 2021 through the National Inpatient Sample(NIS). Frailty status was explored through the criteria of Gilbert’s frailty index. Multivariable regression models helped evaluate differences in short-term outcomes and complications between them.Results:Our study involved 374200 cases of TAVR that were divided into LFR(285425 cases, 76.3%), IFR(86005 cases, 23.0%), and HFR(2770 cases, 0.7%). Compared to patients with LFR, patients with MFR and HFR showed higher odds of several complications, including cardiogenic shock(MFR: aOR 6.933, p

Circulation, Volume 150, Issue Suppl_1, Page A4146434-A4146434, November 12, 2024. Background:PET/CT stress test may be performed to risk stratify patients including those without known coronary artery disease (CAD) who may be at risk for short-term adverse cardiac events. In patients with low- to moderate (LTM) risk for short-term MACE and without a known history of CAD, a small percentage of these patients will undergo a coronary angiogram within 90-days, of which some will be diagnosed with high-grade stenosis. The purpose of this study is to determine factors associated with this approach and findings.Methods:Patients without a history of known CAD (n=43,271) undergoing a PET/CT from 2018-2023 at Intermountain Health, with scan interpreted clinically as LTM short-term risk for adverse cardiac events, and ischemic burden 70% stenosis in any vessel), an a priori list of clinical data and PET/CT results were examined.Results:Within 90 days of the LTM risk PET/CT, 3,163 (8.2%) had a coronary angiogram. Of these, 806 (25.5% of angiograms and 2.1% of total LTM) had high-grade CAD. The PET/CT ancillary findings were associated with the largest odds of performing an angiogram and the presence of high-grade CAD (Tables). Factors most likely to be associated with performing an angiogram were an ischemic burden of 7.5-10% (adjusted-OR [adj. OR]=11.54), coronary artery calcification (CAC) score of >300 (adj.-OR =1.62), and myocardial blood flow (MBF) of MBF 2.3). Other clinical parameters associated, after adjustment, with an angiogram were age, male sex, hypertension, elevated troponin, and inpatient status. Many of the same factors were found to be associated with the identification of high-grade CAD. However, being an inpatient was associated with increased odds of angiogram but a decrease in odds of high-grade CAD.Conclusions:In patients without a known history of CAD who underwent PET/CT clinically adjudicated as LTM short-term risk and ischemic burden

Circulation, Volume 150, Issue Suppl_1, Page A4114970-A4114970, November 12, 2024. Background:Pulsed field ablation (PFA) and high-power short-duration radiofrequency ablation (HPSD) are emerging techniques for treating atrial fibrillation (AF), offering promising results compared to cryoballoon ablation (CBA). This network meta-analysis aims to evaluates the efficacy and safety of PFA, HPSD, and CBA.Method:PubMed, Embase, Cochrane Central Register of Controlled Trials, and EBSCO Information Services were systematically searched for relevant studies until April 2024. The primary outcome is freedom from atrial arrhythmia. A random-effects model was used for data synthesis, and P-scores were employed for outcome ranking. Point estimation (odd ratios) was calculated for comparisons.Results:Fifteen studies were included in our network meta-analysis, involving 5,093 atrial fibrillation patients: 812 (16%), 2,659 (52%), and 1,622 (32%) patients underwent PFA, CBA, and HPSD, respectively. PFA demonstrated the highest efficacy (P-scores 99.3%). Point estimation between PFA and HPSD, and PFA and CBA, were 1.394 (95% CI: 1.047-1.858) and 1.479 (95% CI: 1.134–1.929), respectively. PFA had higher complications compared to HPSD (OR=4.44, 95% CI: 1.405-14.031) and CBA (OR=2.581, 95% CI: 0.992–6.720). HPSD had the shortest fluoroscopic time (P-scores 100%), while CBA had the longest (P-scores 0%). PFA had the shortest procedural time compared to CBA and HPSD with P-scores of 100% 50% and 0%, respectively.Conclusion:PFA showed higher efficacy but higher complication risk than HPSD and CBA. HPSD and CBA demonstrated similar efficacy and safety.

Circulation, Volume 150, Issue Suppl_1, Page A4146327-A4146327, November 12, 2024. Background:Despite advances in treatment strategies for out-of-hospital cardiac arrest (OHCA), prognosis remains poor. The MIRACLE2 score is an established risk stratification tool for cardiogenic OHCA, but its utility in acute coronary syndrome (ACS), a leading OHCA etiology, is unclear.Aims:To validate the prognostic performance of the MIRACLE2 score in OHCA patients with ACS undergoing urgent/emergent percutaneous coronary intervention (PCI).Methods:We conducted a single-center, observational study (COEDO-CPA registry) of consecutive cardiogenic OHCA patients from 2018-2024. Patients with OHCA due to ACS who underwent urgent/emergent PCI were stratified into high-risk (MIRACLE2 score >5), medium-risk (3-4), and low-risk (0-2) groups based on their MIRACLE2 scores. The primary endpoint was 30-day all-cause mortality, compared among risk groups using Kaplan-Meier analysis.Results:Of 124 cardiogenic OHCA patients, 80 with ACS-related OHCA undergoing PCI were analyzed (mean age 64.7 years, 89% male). The mean MIRACLE2 score was 3.2, with 18 high-risk, 30 medium-risk, and 32 low-risk patients. Mechanical circulatory support was used in 58%. The high-risk group tended to be older with higher lactate levels, worse renal function, elevated D-dimer, and longer cardiopulmonary resuscitation duration compared to lower-risk groups. Kaplan-Meier analysis demonstrated a graded increase in 30-day mortality across risk groups, with effective risk stratification by the MIRACLE2 score (log-rank p=0.003).Conclusion:Among OHCA patients with ACS undergoing PCI, the MIRACLE2 score effectively stratified short-term mortality risk. This validated risk stratification tool could guide treatment strategies and resource allocation in this critically ill population. Incorporating the MIRACLE2 score into OHCA management pathways may optimize care for ACS-related OHCA.

Circulation, Volume 150, Issue Suppl_1, Page A4145961-A4145961, November 12, 2024. Introduction:Approximately 20% of ischemic strokes are linked to a cardioembolic source, with 80% of cardioembolic strokes being attributed to atrial fibrillation. This study aimed to investigate the impact of non-valvular atrial fibrillation (NVAF) on mortality and recurrent stroke following a minor stroke event, considering AF as the most prevalent sustained cardiac rhythm disorder associated with stroke.Methods and Materials:Consecutive patients experiencing minor acute ischemic stroke (NIHSS

Circulation, Volume 150, Issue Suppl_1, Page A4139976-A4139976, November 12, 2024. Introduction:In pulmonary vein isolation (PVI), the carina is often refractory to ablation and require linear ablation, and some patients have epicardial connections.Hypothesis:High-power Shor-duration (HP-SD) ablation can prevent gap formation, and high unipolar-voltage-area (HUV), defined >2.7 mV, will identify the epicardial connection site.Aims:To investigate the impact of HP-SD ablation on durable PVI and the efficacy of HUV for the prediction of epicardial connection site.Methods:Ninety-three atrial fibrillation (AF) patients who underwent successful PVI were enrolled. Forty-one patients underwent HP-SD ablation, while fifty-two patients underwent conventional ablation. First pass isolation was achieved in 66 patients, while the remaining 27 patients needed carina ablation. The epicardial conduction gap (EG) of the PVI line was defined as the continuous propagation pattern across the PVI line under the high right atrial pacing. The epicardial connection (EC) was defined that the propagation pattern was defined as a centrifugal pattern with the earliest site located around the mid-carina, more than 5 mm far from PVI line.Results:Carina ablation following PVI was needed more frequently in conventional ablation group than in HP-SD group (38% vs. 17%, P = 0.020). However, there was no statistical difference in EC between HP-SD and conventional ablation groups ［2 of 41 (4.8%) in HP-SD vs. 3 of 52 (5.7%) in conventional, P = 0.852］. This suggests that HP-SD ablation could suppress EG formation more effectively. Among the 5 patients with EC, 4 patients (80%) had HUV adjacent to the earliest activation site at the mid-carina (3 in right and 1 in left). Notably, the EC was eliminated by ablation at the HUV but not at the earliest activation site. During a one-year follow-up, 7 patients experienced AF recurrence. Patients who underwent HP-SD ablation showed lower tendency for recurrence compared to those with conventional ablation (4.8% vs 13.4%, P = 0.126). Notably, no patients who underwent EC ablation in the HP-SD ablation group experienced recurrence, whereas all patients in the conventional ablation group experienced recurrence (0% vs 100%). Among patients requiring carina ablation, 1 of 2 in the HP-SD group and 6 of 7 in the conventional group experienced recurrence (50% vs. 85.7%).Conclusion:HP-SD ablation was effective to prevent EG and EC, and HUV was useful indicator of epicardial breakthrough site to endocardium.

Circulation, Volume 150, Issue Suppl_1, Page A4136554-A4136554, November 12, 2024. Background:In 2023, the AHA published the PREVENT equations for estimating atherosclerotic cardiovascular disease (ASCVD) risk in adults aged 30-79 years.Research Questions:In young adults aged 20-39 years, does PREVENT improve risk prediction for 10- and 30-year ASCVD compared with existing risk assessment tools recommended in the current US guidelines (i.e., Pooled Cohort Equations [PCEs] and Pencina et al. equations)?Aims:To compare the performance of PREVENT vs. PCEs in predicting 10-year ASCVD, and PREVENT vs. Pencina equations in predicting 30-year ASCVD in young adults.Methods:We analyzed data from two complementary sources: (1) pooled data from two large cohorts: Coronary Artery Risk Development in Young Adults (CARDIA) and Framingham Heart Study (FHS; including the Offspring, Third Generation, Omni 1, and Omni 2 cohorts), and (2) electronic health records from Kaiser Permanente Southern California (KPSC). We included adults aged 20-39 years without a history of ASCVD at baseline. The outcome was incident ASCVD (defined as myocardial infarction, fatal coronary heart disease, fatal and nonfatal stroke) at 10 or 30 years. Model discrimination (Harrell’s C) and mean calibration (estimated as the ratio of predicted to observed event rates) were calculated for the overall population and stratified by sex and race/ethnicity.Results:We included 7,606 young adults (mean age 29 years, 53% female, 30% Black) from the pooled cohorts, and 284,667 (mean age 32 years, 61% female, 8% Black, 46% Hispanic) from KPSC. When predicting 10-year risk, PREVENT improved discrimination in both the pooled cohort (ΔHarrell’s C=0.052; 95% CI: 0.014, 0.095) and KPSC (ΔHarrell’s C=0.039; 95% CI: 0.028, 0.049) compared with the PCEs. PREVENT had good calibration (mean calibration ranged from 0.77 to 1.54), whereas the PCEs overestimated 10-year risk (mean calibration ranged from 1.99 to 4.82). When predicting 30-year risk, discrimination was similar for PREVENT and Pencina equations, but both algorithms underestimated 30-year risk with PREVENT showing worse calibration (mean calibration 0.61).Conclusion:PREVENT improved 10-year ASCVD risk prediction in young adults compared to the PCEs but underestimated 30-year risk.

Circulation, Volume 150, Issue Suppl_1, Page A4140686-A4140686, November 12, 2024. Background:Comorbid diabetes mellitus (DM) is associated with worse outcomes in patients with chronic limb-threatening ischemia (CLTI). Both lower extremity bypass (LEB) and peripheral vascular interventions (PVI) have demonstrated improved outcomes in peripheral artery disease (PAD). However, comparative effectiveness data for LEB versus PVI in patients with CLTI and DM is limited.Objective:This study aimed to evaluate and compare 30-day and 90-day (1) all-cause mortality, and (2) major amputation rates among patients with CLTI and comorbid DM undergoing LEB versus PVI.Methods:Patients undergoing LEB and PVI were identified from the Vascular Quality Initiative registry, linked with Medicare claims outcomes data. Propensity scores were generated using 12 variables, and a 1:1 matching method was employed. The 30-day and 90-day mortality risks for LEB versus PVI were evaluated using Kaplan-Meier survival analysis and Cox proportional hazards models, incorporating interaction terms for DM. For amputation outcomes, cumulative incidence functions and Fine-Gray competing risks models were employed, with interaction terms for DM included.Results:Among 4,210 patients undergoing LEB or PVI (2,105 in each group), the mean age was 70.9 ± 10.9 years, with 69.3% being male and 76.4% white. DM was present in 62.3% (2,662 patients). In patients with DM, 30-day all-cause mortality rates were comparable between the LEB and PVI groups (2.1% vs. 2.6%; log-rank p-value=0.844). However, LEB was associated with significantly lower 90-day all-cause mortality rates compared to PVI (5.1% vs. 7.6%; log-rank p-value=0.013). Additionally, LEB was associated with a lower risk of 30-day major amputation rates compared to PVI (2.7% vs. 4.2%; p=0.049), though no significant difference was observed in 90-day major amputation rates (9.4% vs. 10.9%; p=0.196).Conclusion:Among patients with CLTI and comorbid DM, LEB was associated with a lower risk of 30-day major amputation rates and 90-day all-cause mortality compared to PVI. These findings provide contemporary insights into the management of CLTI in diabetic patients, supporting informed shared decision-making for those often considered high-risk for surgical intervention.

Circulation, Volume 150, Issue Suppl_1, Page A4141813-A4141813, November 12, 2024. Introduction:In 2021, the American Society of Nephrology Task Force recommended using the new CKD-EPI 2021 formula to estimate the glomerular filtration rate (eGFR) and to classify CKD. Evidence to compare the efficacy of this new formula with the current utilized formula, including MDRD and CKD-EPI 2009, in predicting the short-term outcomes of Asian patients with acute heart failure (AHF) is lacking.Hypothesis:The eGFR calculated by the CKD-EPI 2021 formula predicts short-term outcomes of patients with AHF more accurately than those calculated by the MDRD and CKD-EPI 2009 formulas.Methods:We conducted a pilot retrospective cohort study from January 1, 2023, to December 31, 2023, at Can Tho Central General Hospital in Can Tho, Vietnam. Our study included patients aged ≥18 who were admitted with AHF, NT-pro BNP levels exceeding 300 pg/mL, and creatinine result within 24 hours of admission. eGFR was calculated using 3 different formulas such as CKD-EPI 2021, CKD-EPI 2009, and MDRD. The short-term outcome was determined by 3-months post-discharge all causes mortality.Results:The final cohort comprised 146 patients, with a mean age of 65.6 ± 14.2 years and male proportion of 46%. Significant correlations were observed among the three formulas, with the strongest correlation observed between the CKD-EPI 2021 and 2009 formulas. In predicting short-term outcomes, the CKD-EPI 2021 and CKD-EPI 2009 formulas demonstrated superior performance compared to the MDRD formula, with respective area under the curve values of 0.634, 0.635, and 0.607. After multivariable analysis, from 90mL/min/1.73m2, every 10 ml/min/1.73 m2decrease in eGFR calculated by CKD-EPI 2021, CKD-EPI 2009, and MDRD was associated with a 32% (95% CI: 9-49), 26% (95% CI: 4-47), and 30% (95% CI: 8-47) increase in the odds of all-cause mortality among patients with AHF. Only CKD-EPI 2021 formula showed significant predictive prognostic value (log-rank test, p=0.049) (Figure).Conclusion:The CKD-EPI 2021 formula showed superior prognostic efficacy for short-term outcomes in Asian patients with acute heart failure (AHF) compared to current formulas. Further research involving larger patient cohorts and longer-term outcomes is warranted.

Circulation, Volume 150, Issue Suppl_1, Page A4144822-A4144822, November 12, 2024. Background:The relationship between anion gap (AG) and short-term mortality in intensive care unit (ICU) sepsis patients complicated by pulmonary hypertension (PH) remains unclear.Methods:Retrospective analysis of incident sepsis patients complicated by PH first admitted to ICU in MIMIC database (2008 to 2019) were enrolled. Short-term outcomes include in-hospital mortality and 28-day mortality. According to the AG value (17.0 mmol/L), patients were divided into high and low AG groups. The Kaplan-Meier survival curve was used to compare the cumulative survival rates of the high and low groups using the log-rank test. Multivariable Cox regression analyses were constructed to assess the relationship between AG and short-term outcomes in sepsis patients complicated by PH.Results:2012 sepsis patients with pulmonary hypertension were included. The in-hospital mortality rates (11.4%) and 28-day mortality rates (12.8%) in the high AG group were higher than those in the low AG group (5.0% or 7.2%, respectively;P< 0.001). The Kaplan-Meier curve showed that the in-hospital and 28-day cumulative survival rates were lower in the high AG group than that in the low AG group (P< 0.001). Multivariable Cox regression analysis confirmed that elevated AG was an independent risk factor of in-hospital mortality, 28-day mortality, length of stay in ICU and hospital. The relationship between elevated AG and in-hospital mortality remain stable after subgroups analyses.Conclusions:Elevated serum AG is associated with increased risk-adjusted short-term mortality in sepsis patients complicated by PH, and it may remind clinicians to identify patients with poor prognosis as early as possible.

Circulation, Volume 150, Issue Suppl_1, Page A4139675-A4139675, November 12, 2024. Background:The net benefit of aspirin cessation in older adults remains uncertain. This study aimed to use observational data to emulate a randomized trial of aspirin cessation versus continuation in older adults without cardiovascular disease (CVD).Methods:Post-hoc analysis using a target trial emulation framework (Table 1) applied to the immediate post-trial period (2017-2021) of a study of low-dose aspirin initiation in 19,114 adults aged 70 years and older (ASPREE; NCT01038583). Participants from Australia and US were included if they were free of CVD at the start of the post-trial intervention period (time zero, T0) and had been taking open-label or randomized aspirin immediately before T0 (Fig 1A). The two groups in the target trial were: aspirin cessation (participants who were taking randomized aspirin immediately before T0; assumed to have stopped at T0 as instructed) versus aspirin continuation (participants on open-label aspirin at T0 regardless of their randomized treatment; assumed to have continued at T0). The outcomes after T0 were incident CVD, major adverse cardiovascular events (MACE), all-cause mortality, and major bleeding during 3, 6, and 12 months (short-term), and 48 months (long-term) follow-up. Hazard ratios (HRs) comparing aspirin cessation to continuation were estimated from propensity-score (PS) adjusted Cox proportional-hazards regression models.Results:We included 6,103 CVD-free participants (cessation: 5,427, continuation: 676). Participant selection flow chart is presented inFig 1B. Over both short- and long-term follow-up, aspirin cessation versus continuation was not associated with elevated risk of CVD, MACE and all-cause mortality (HRs, at 3 and 48 months respectively were, 1.23 and 0.73 for CVD; 1.11 and 0.84 for MACE; 0.23 and 0.79 for all-cause mortality, p >0.05) but cessation had a reduced risk of incident major bleeding events (HRs at 3 and 48 months, 0.16 and 0.63, p

Circulation, Volume 150, Issue Suppl_1, Page A4143745-A4143745, November 12, 2024. Background:Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is a complex procedure to restore blood flow in completely occluded coronary arteries with the aim of improving symptoms and quality of life. While CTO-PCI success rates have increased owing to advancements in antegrade and retrograde techniques, the choice of approach remains crucial. The antegrade approach is often the initial method chosen because of its relative simplicity, whereas the retrograde approach is considered in more complex cases or when the antegrade approach fails.Aims:The data suggest that the retrograde approach is associated with higher periprocedural complications, although the reports are conflicting. Our meta-analysis aimed to compare the efficacy and safety of the antegrade and retrograde approaches for CTO-PCI.Methods:A comprehensive literature search was conducted on PubMed, Embase, Google Scholar, and Scopus from inception until June 5, 2024. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated using Review Manager, with a p-value of

Circulation, Volume 150, Issue Suppl_1, Page ASu1107-ASu1107, November 12, 2024. Introduction:Opioid overdose (OD) is a growing cause of cardiac arrest in the US, spurred by the rise of illegally manufactured fentanyl and analogs. Naloxone is a reversal agent that can be administered by bystanders. Intra-nasal (IN) naloxone is now widely available in pharmacies across the US. Despite increasing access, minority populations remain disproportionately affected by drug overdose deaths. There are many free online opioid OD educational videos. Digital media can be a powerful tool for mass education, but the effectiveness is unknown.Research Question and Aims:The goal of this study was to evaluate online opioid overdose videos for content and gender/racial representation.Methods:We performed an online search with the query “how to give Narcan” (popular term for IN naloxone). Results were limited to the first 52 Google, 50 YouTube, and 60 TikTok videos. Exclusion criteria included: animal victim, duplicate, or no mention of naloxone. For each video, 2 reviewers evaluated content and identified the race and gender of featured characters. Disagreements were resolved through consensus. The race and gender of featured characters was compared using a two proportion z-test. Inter-rater reliability (IRR) for each data point was calculated using the arithmetic mean of Cohen’s kappa.Results:Of 121 videos, the majority (87.6%) mentioned naloxone as a treatment for opioid OD; 62.8% provided instruction on how to administer IN naloxone, and 4.1% featured a testimonial. Only 43.0% provided a realistic visual demonstration of IN naloxone administration; 25.6% showed a realistic re-enactment of opioid overdose, and even fewer (19.0%) showed the dramatic response to naloxone. IRR was high for all categories.Videos predominantly featured white compared to non-white-appearing characters in both the victim (75.5 v. 17.8%, p< 0.00001) and rescuer roles (72.5 v 21.6%, p

Circulation, Volume 150, Issue Suppl_1, Page A4133654-A4133654, November 12, 2024. Introduction:Conventional cardiovascular disease (CVD) risk scores are inaccurate for prostate cancer patients (PC); the Guha-Stabellini machine learning (GS-ML) score shows promise but lacks external validation.Hypothesis:The GS-ML score is superior to conventional CVD scores in patients with PC.Aim(s):To conduct external validation of the GS-ML score in patients diagnosed with PC.Methods:The validation used holdout data from Seidman Cancer Center’s CAISIS platform (internal validation cohort) and RADICAL PC1 (external validation cohort; a prospective study of men diagnosed with PC within 1 year or starting ADT within 1 month of enrollment), matching covariates with the GS-ML score. With limited follow-up, short-term CVD (2,000 days from PC diagnosis) was the outcome. Performance was assessed via area under the receiver operating characteristic curve (AUC) with assistance from Youden statistic cutoff, comparing metrics with ACC/AHA pooled cohort equations (PCE), SCORE-2, and AHA-PREVENT scores. Atherosclerotic cardiovascular disease (ASCVD) included non-fatal ischemic stroke and myocardial infarction. CVD included ASCVD and heart failure.Results:We included 2,495 patients from RADICAL PC1 and 1,506 from the internal validation cohort (Table 1). In the internal validation cohort, the CVD AUCs were 0.58, 0.49, 0.65, 0,73, and 0.75 for PCE, SCORE2, PREVENT simple, PREVENT enhanced, and GS-ML score, respectively. In RADICAL PC1, the AUCs for CVD were 0.60, 0.43, 0.67, and 0.64 for PCE, SCORE2, PREVENT simple and GS-ML score, respectively. For ASCVD, internal validation cohorts’ AUCs were 0.63, 0.62, 0.66, 0.73, and 0.67 for PCE, SCORE2, PREVENT simple, PREVENT enhanced, and Guha-Stabellini, respectively. The RADICAL PC1 ASCVD AUCs were 0.64, 0.46, 0.65, and 0.61, for PCE, SCORE2, PREVENT simple and GS-ML scores, respectively,Conclusion(s):The GS-ML score was validated for PC patients, showing superior performance to PCE and SCORE2, and similar performance to AHA-PREVENT in predicting CVD. The European Cardio-Oncology guidelines should reconsider using SCORE2 for PC patients. Further improvement and validation with nationally representative datasets are needed to corroborate these findings and enhance the generalizability of the GS-ML score.

Circulation, Volume 150, Issue Suppl_1, Page A4147094-A4147094, November 12, 2024. Background:Direct-acting oral anticoagulants (DOACs) have emerged as a preferred alternative to Vitamin K Antagonists (VKAs) for patients with atrial fibrillation (AF). However, the exclusion of patients with liver cirrhosis (LC) from recent clinical trials leaves the efficacy and safety of DOACs in this population unclear.Hypothesis:DOACs are more effective and have a better safety profile compared to VKAs in patients with AF and LC.Methods:Following the PRISMA guidelines, we searched PubMed, Cochrane Library, Embase, Scopus, Web of Science, and CNKI databases for randomized clinical trials (RCTs) and observational studies comparing DOACs and VKAs in patients with AF and LC. Statistical analysis was performed using the metafor package in R software. Heterogeneity was assessed using the I2 statistic, and a random-effects model was employed to calculate pooled Hazard Ratios (HRs). For trivial heterogeneity (I2