CYP2C19 genetic polymorphisms impact the antiplatelet effect of clopidogrel and associate with ischemic and bleeding risk in patients undergoing percutaneous coronary intervention (PCI). This study aimed to evaluate the association of CYP2C19 and platelet reactivity (PR) with these risks, in atrial fibrillation (AF) patients undergoing PCI,treated with an oral anticoagulation (OAC) and clopidogrel. This two-center prospective cohort study included patients with AF and OAC undergoing PCI. Carriers of ≥ 1 loss-of-function (LOF) allele were classified as poor/intermediate metabolizers (PM/IM), whereas carriers of ≥ 1 gain-of-function allele without LOF alleles were classified as rapid metabolizers (RM). PR was assessed by thromboelastography (TEG) and/or multiple electrode aggregometry (MEA). The primary outcome included death, MI, or stroke at 6 months ±2 weeks; the secondary outcome consisted of non-major clinically relevant (NMCR) or major bleeding. Among 283 patients (median age 78 years; 72% male), 73 (26%) were PM/IM, 108 (38%) were NM, and 102 (36%) were RM. PM/IM status was not significantly associated with the primary ischemic outcome (PM/IM: 6 [8.2%] vs. NM + RM: 16 [7.6%], p = 0.869), but any bleeding rates were numerically lower. While there was a trend for association of high platelet reactivity (HPR) with the ischemic outcome (OR 2.005 [95% CI 0.820-4.902], p = 0.127), low platelet reactivity (LPR) was associated with major bleeding (OR 2.646 [95% CI 1.075-6.509], p = 0.034). PM/IM status did not detect an increased ischemic risk but might, however, protect from bleeding risk in AF patients undergoing PCI. HPR might indicate a higher ischemic risk, while LPR was associated with major bleeding.

Oral P2Y12 inhibitors only versus cangrelor in critically ill patients requiring percutaneous coronary interventions supported by microaxial flow pumps.

Sex differences in venoarterial extracorporeal membrane oxygenation utilisation and clinical outcomes in Australia.

Predictors of bleeding-related in-hospital complications after coronary angiography and percutaneous coronary intervention: A single-center retrospective cohort study in Iran.

Drug-Coated Balloon Versus Drug-Eluting Stent for Coronary Revascularization in Patients With Chronic Kidney Disease: A Real-World Propensity-Matched Study.

The impact of coagulopathy on prognosis in critically ill patients with sepsis: A nationwide cohort study.

Selective screening falls short: A review of universal screening for blunt cerebrovascular injury.

This study aims to use routinely collected health data and trial emulation methodology to inform the design of a pragmatic randomized controlled trial (RCT) in people requiring multivessel coronary revascularization with severe symptomatic multivessel disease and high-risk characteristics, typically underrepresented in previous RCTs. Hospital episode statistics (HES) linked to Office for National Statistics will be the main data source. The study population is patients who require multivessel myocardial revascularization with at least one of the following high-risk characteristics: age >75 years, female, diagnosed with acute coronary syndrome, heart failure, chronic kidney disease, peripheral vascular disease, or intermediate frailty risk. The intervention procedure is coronary artery bypass grafting (CABG) and the control (reference) is percutaneous coronary intervention (PCI). Outcomes include all-cause and cardiovascular (CV) death, CV hospitalization, major adverse cardiovascular events, and major vascular complications or bleeding within 5 years of the index procedure. This study includes 3 stages of statistical analyses: (1) latent class analysis (LCA) to identify mutually exclusive patient clusters (latent classes) representing different clinical phenotypes, (2) instrumental variable analysis (IVA) to estimate the average treatment effect (ATE) in the whole population and each patient cluster; and (3) repeating stage 2 in an emulated trial population obtained by matching the HES population with individual participant data from an RCT. We will then co-design the protocol for a definitive clinical trial in partnership with patients, public, and stakeholders. This study introduces a novel, stepwise data science framework that integrates machine learning (unsupervised learning through LCA), causal inference, and trial emulation methods applied in big data, to design a future stratified and adaptive RCT of CABG versus PCI in high-risk patients. Our proposed approach fosters new collaborations among data scientists, trial methodologists, clinicians, and patient and public representatives in complex trial designs for diverse, high-risk populations. This study represents a new framework for co-production in trials of cardiovascular interventions, which offers a scalable model and has the potential to transfer to other disease areas. URL: https://www. gov/study/NCT05853536. Unique identifier: NCT05853536.

Whether long-term oral anticoagulation (OAC) is necessary after apparently successful atrial fibrillation (AF) ablation remains uncertain. Guidelines recommend continuation based on CHA2DS2-VASc score rather than procedural success, yet contemporary evidence, including randomized trials, has produced conflicting results. We aimed to provide an updated and comprehensive assessment of OAC discontinuation following AF ablation. We conducted a systematic review and meta-analysis in patients who discontinued versus continued OAC after AF ablation. Outcomes included thromboembolic events (TE) and major bleeding events (MBE). Random-effects models with Hartung-Knapp correction were applied. Heterogeneity, publication bias, influence analyses, subgroup analyses, and risk-of-bias domains were assessed. In 28 studies (267 443 patients), OAC discontinuation significantly reduced the composite of TE and MBE (RR 0.44, 95% CI 0.32-0.61), driven by a marked decrease in bleeding (RR 0.25, 95% CI 0.16-0.39), without excess thromboembolic risk (RR 0.84, 95% CI 0.64-1.12). Findings remained consistent across subgroup analyses (study design, CHA2DS2-VASc, geographic region), with sensitivity and meta-regression confirming robustness and no significant effect modifiers. Funnel plots showed no significant asymmetry for TE, whereas MBE demonstrated evidence of small-study effects. Discontinuation of OAC after successful AF ablation markedly reduces MBE without a statistically significant increase in TE, highlighting the need for individualized post-ablation anticoagulation strategies. Randomized trials are needed to confirm the safety of tailored oral anticoagulant discontinuation in selected patients, supported by careful long-term follow-up and shared decision-making.

Background: Critically ill adults are more commonly being admitted to intensive care units (ICU) with a recent history of direct oral anticoagulant (DOAC) use. No consensus guidance exists on optimal anticoagulation strategies in critically ill adults with non-valvular atrial fibrillation (NVAF) on DOAC's prior to ICU admission, and there is considerable variability in clinical practice. Objective: To evaluate rates of major bleeding and thrombosis between 2 anticoagulation strategies for NVAF upon ICU admission: package insert (continuation of oral or parenteral anticoagulation per manufacturer recommendations) vs non-package insert (prophylactic dosing or delayed therapeutic anticoagulation). Study design: This was a retrospective cohort study conducted from January 2019 to August 2023. Patients with NVAF and objective evidence of DOAC exposure within 48 hours of ICU admission were included. Those admitted to the ICU for a bleeding event or who received anticoagulation for indications other than NVAF were excluded. Results: A total of 353 patients met inclusion criteria (122 vs 231 in the package insert and non-package insert groups, respectively). There was no significant difference in the composite incidence of major bleeding and stroke or systemic embolism between groups (4.1% in package insert vs 6.1% in non-package insert; P = 0.437). Conclusion: This study demonstrated no difference in the incidence of major bleeding, in-hospital stroke, or systemic embolism with a package insert vs a non-package insert approach to anticoagulation in critically ill patients receiving DOAC therapy for atrial fibrillation. However, more studies are needed to develop evidence-based guidance on anticoagulation management in this population.

Atrial fibrillation (AF) is a prevalent comorbidity among patients undergoing transcatheter aortic valve implantation (TAVI); however, its prognostic implications remain uncertain. This study aimed to elucidate the impact of preprocedural AF on clinical outcomes following TAVI in patients with aortic stenosis (AS). We conducted a single-center, retrospective cohort study comprising 297 consecutive AS patients who underwent TAVI (mean age 83 ± 4years; 69% female). Pre-existing AF was identified in 89 (30%) patients. Patients were stratified into two groups based on the presence or absence of AF, and propensity score matching (PSM) was employed, resulting in 68 matched pairs. The study endpoint was the incidence of net adverse clinical events (NACE) and all-cause mortality. NACE was defined as a composite of all-cause mortality, non-fatal myocardial infarction, non-fatal ischemic stroke, systemic thromboembolism, valve thrombosis, and major bleeding events. These clinical outcomes were analyzed according to the presence and subtype of pre-existing AF and further stratified across body mass index (BMI) categories. To further assess the combined impact of AF and BMI, patients were additionally categorized into four groups according to the presence or absence of AF and low BMI (< 18.5kg/m2), and multivariable Cox regression analysis was performed across these groups. The median duration of follow-up was 2.3 [1.0-3.7] years. While baseline characteristics, including age and gender, were comparable between groups, patients with pre-existing AF exhibited a higher prevalence of prior heart failure hospitalizations and reduced renal function. There were no statistically significant differences in the incidence of NACE and all-cause mortality between the AF and non-AF groups, both before and after PSM. However, among patients with AF, those with a low BMI < 18.5kg/m2 experienced a significantly higher rate of adverse clinical events compared to those with normal or high BMI. This was supported by multivariable analysis. Although preprocedural AF was not independently associated with adverse clinical outcomes following TAVI, the coexistence of AF and low BMI was linked to significantly worse prognosis. These findings suggest a potential synergistic effect warranting further investigation and individualized risk stratification.

Outcomes of venous-arterial extracorporeal membrane oxygenation (VA-ECMO) therapy in acute pulmonary embolism. High-risk pulmonary embolism (PE) has a high mortality risk. VA-ECMO provides essential cardiopulmonary support, although data outcomes remain limited. We sought to describe the characteristics and clinical outcomes of patients supported with VA-ECMO for the management of high-risk PE. We retrospectively analyzed outcomes of adult patients treated with VA-ECMO for high-risk PE at the University of Minnesota between January 2015 and May 2024. High-risk PE was defined by the European Society of Cardiology criteria. Clinical, demographic, procedural, and outcome data were analyzed. Mortality predictors were assessed using logistic regression. Of 1350 patients supported by VA-ECMO, 58 (4.3%) presented with high-risk PE (69% cardiac arrest, 31% shock). Mortality was significantly higher among patients cannulated for cardiac arrest than for shock (72.5% vs. 33.3%, P = 0.005). An independent predictor of mortality was out-of-hospital cardiac arrest (OR 6.67, 95% CI 1.15-38.7, P = 0.035). The duration of CPR was shorter among survivors (25.9 vs. 44.2min, P = 0.02). Neither catheter-directed therapy nor systemic thrombolysis was associated with survival. Major bleeding occurred in 67% of patients and was not significantly associated with mortality. Neurologic injury was the leading cause of death in cardiac arrest patients; multiorgan failure predominated in the shock group. Despite the use of VA-ECMO, mortality in high-risk PE remains elevated, but differed by indication for cannulation. Survival was higher in patients presenting with shock, in-hospital cardiac arrest, shorter CPR duration, and sustained return of spontaneous circulation. Further research is needed to define the role of VA-ECMO and adjunctive therapies across varied clinical presentations.

Edoxaban is a direct oral anticoagulant used for stroke prevention in patients with atrial fibrillation (AF) and treatment of venous thromboembolism. We examined the relationship between trough edoxaban concentrations (E-trough) and prothrombin time (PT) and major bleeding in very old Japanese patients with atrial fibrillation and high bleeding risk. In this post hoc analysis of the multicenter, randomized, double-blind, placebo-controlled ELDERCARE-AF (Study of DU-176b Aged 80 Years or Older) trial, patients were randomly assigned 1:1 to edoxaban 15 mg or placebo once daily. After 8 weeks of treatment, E-trough was determined and the incidence of major bleeding examined in each quartile. The incidence of major bleeding by PT was also examined. Data were obtained from 427 patients. E-trough (ng/mL) was ≤9.24 in the first quartile (107 patients), >9.24 to ≤13.6 in the second (111 patients), >13.6 to ≤21.6 in the third (103 patients), and >21.6 in the fourth (106 patients). Older age, lower body weight, lower creatinine clearance, and the presence of congestive heart failure were independent predictors of higher E-trough. Higher E-trough was associated with greater incidence of major bleeding (0.8%, 1.9%, 3.4%, and 4.7%/year, respectively, P=0.0408). There was a significant positive correlation between E-trough and PT (r=0.426, P<0.0001). Significantly more major bleeding events occurred in the longer (>13 seconds) versus shorter (≤13 seconds) PT subgroups (4.61% versus 0.98%/year, P=0.0060). Several factors were associated with higher E-trough and increased risk of major bleeding events. PT >13 seconds may be a useful predictor of the development of major bleeding. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02801669.

The balance between thromboembolic complications and bleeding risk in anticoagulated patients with atrial fibrillation remains challenging, with left atrial appendage occlusion (LAAO) representing a potential alternative. Our prospective multicenter study aimed to evaluate the feasibility, safety, technical, and procedural outcomes of the contemporary practice of stand-alone LAAO. The SALAMANDER (Stand-Alone Left Atrial Appendage Occlusion for Thromboembolism Prevention in Nonvalvular Atrial Fibrillation Disease) registry is a real-world, multicenter, observational cohort study conducted at 16 cardiac centers in Europe between 2010 and 2024, evaluating the safety and efficacy of LAAO using contemporary devices. A total of 1660 patients were enrolled, with a median age of 76 (interquartile range, 70-81) years and 38% being women. The median CHA2DS2-VASc score was 4 (interquartile range, 3-5). The most common indication for LAAO was significant bleeding (83.7% of patients), most frequently during treatment with direct oral anticoagulants (68.8%) more than vitamin K antagonists (24.9%). The predominant bleeding sites were the lower (27.9%) and upper (21.7%) gastrointestinal tracts, with 17.4% having a history of hemorrhagic stroke. The most common antithrombotic regimen before the procedure was direct oral anticoagulants (48.9%), while postprocedural therapy most often included dual antiplatelet therapy (50%). The technical success rate was 95.5%, with residual leak (2.2%) and tamponade (1.4%) as the main causes of failure. Procedural success was 90.5%, most often limited by vascular complications (3.7%), periprocedural death (1.1%), and major bleeding (0.7%). Technical and procedural success rates did not differ significantly between the devices used. In this large prospective cohort, technical and procedural success rates were similar across all LAAO devices, suggesting comparable safety and efficacy. Postprocedural therapy typically involves dual antiplatelet therapy, with all patients requiring some pharmacological treatment. URL: https://www.clinicaltrials.gov; Unique identifier: NCT05144958.

Emerging data suggest that, in patients with chronic coronary syndromes (CCS), clopidogrel provides superior antithrombotic protection compared with aspirin for secondary prevention, without an associated increase in bleeding risk. The consistency of the observed benefits across ethnicities remains uncertain. Randomized controlled trials (RCTs) comparing aspirin vs clopidogrel for secondary prevention in patients with CCS were screened. The primary endpoint was trial-defined major adverse cardiovascular events (MACE). Prespecified subgroup interaction by ethnicity (East Asian vs non-East Asian) was performed. Trial sequential analysis was used to assess the statistical power of the results. Seven RCTs were included, encompassing 30 165 patients, of whom 75.1% were East Asians. Median follow-up was 36.0 months. Overall, clopidogrel was associated with significant reductions in MACE (incidence rate ratio [IRR] 0.83, 95% confidence interval [CI] 0.69-0.99) and net adverse clinical events (IRR 0.83, 95% CI 0.69-0.99), compared with aspirin. There were no differences between groups in major bleeding, myocardial infarction, or mortality. The results were consistent in the East Asian population, whereas a significant interaction by ethnicity was observed for MACE (East Asians: IRR 0.76, 95% CI 0.59-0.98; non-East Asians: IRR 1.00, 95% CI 0.74-1.36; Pint = 0.010) and mortality (Pint = 0.014), with no significant benefits observed in non-East Asian patients. The analyses were statistically powered for most outcomes in East Asian populations but for none in non-East Asian populations. In patients with CCS, the overall body of evidence suggests improved outcomes with clopidogrel compared with aspirin, without an apparent effect on mortality. However, a high level of confidence in these findings is currently limited to East Asian populations, and additional evidence is needed to clarify their applicability to non-East Asian patients. PROSPERO (CRD420251145176).

Obese patients hospitalized for surgery are at high risk of venous thromboembolism (VTE). The optimal dose and duration of thromboprophylaxis with low molecular weight heparin for these patients are uncertain. To assess the time-course, rates and risk factors for VTE and major bleeding (MB) in a population of surgical patients with obesity receiving pharmacological thromboprophylaxis with enoxaparin. Patients with body mass index (BMI) > 30kg/m2 hospitalized with surgeries between 2010 and 2021 who received thromboprophylaxis with enoxaparin were selected from the US Optum database. Exclusion criteria were VTE, MB, or surgery in previous 90-days, and ongoing anticoagulant treatment or dual antiplatelet therapy. VTE and MB event rates over a 90-day follow-up post enoxaparin initiation were estimated via the Kaplan-Meier (KM) method. Risk factors associated with outcome events were identified via Cox proportional hazard models. A total of 30,492 patients met selection criteria, 12,058 patients received the standard dose, with 18,300 receiving higher doses. KM event rates at 90-days for VTE and MB were 2.5% and 1.2%, respectively. The highest VTE rates were observed in patients hospitalized for thoracic surgery (4.9%). History of VTE was the strongest predictor of post-surgery VTE (HR 5.62, 95% CI 4.71-6.7) while history of MB was the strongest predictor of post-surgery bleeding (HR 2.62, 95% CI 1.29-5.32). The rates of VTE are non-negligible in surgical patients with obesity receiving thromboprophylaxis with enoxaparin. Individual risk stratification is warranted to identify optimal doses/duration of pharmacologic thromboprophylaxis.

To estimate major clinical event rates for patients with atrial fibrillation (AF) and atherosclerotic disease treated with edoxaban in routine practice, and to evaluate how well such patients were represented in ENGAGE AF-TIMI 48, the seminal randomized trial comparing edoxaban against warfarin for AF. ETNA-AF-Europe is a prospective cohort of AF patients receiving edoxaban in routine care. We compared patients with coronary or peripheral artery disease (CAD/PAD) to: (1) those without CAD/PAD in ETNA-AF-Europe, and (2) CAD/PAD patients in ENGAGE AF-TIMI 48. Of 13,164 patients in ETNA-AF-Europe, 23.3% had CAD/PAD. Compared with those without, patients with CAD/PAD had higher rates of stroke/systemic embolism (0.87%/year vs. 0.59%/year; HR 1.5, 95%-CI 1.14-1.88), acute coronary syndrome (1.24%/year vs. 0.37%/year; HR 3.3, 95%-CI 2.60-4.27), major bleeding (1.06%/year vs. 0.81%/year; HR 1.3, 95%-CI 1.04-1.63), cardiovascular death (1.59%/year vs. 0.85%/year; HR 1.9, 95%-CI 1.54-2.26), and all-cause death (6.02%/year vs. 3.53%/year; HR 1.7, 95%-CI 1.55-1.89). Compared with CAD/PAD patients in ENGAGE-AF TIMI-48, those in ETNA-AF-Europe had fewer cardiovascular comorbidities, less prevalent aspirin use (20.2% vs. 50.3%), and lower rates of stroke/systemic embolism (0.87%/year vs. 1.5%/year), major bleeding (1.04%/year vs. 3.0%/year), and cardiovascular death (1.59%/year vs. 3.7%), but higher non-cardiovascular mortality (4.43%/year vs. 1.6%/year). In routine practice, deaths and bleeding were the most common events in edoxaban-treated patients with AF. This pattern was consistent between those with and without atherosclerosis. ENGAGE-AF TIMI-48 participants with CAD/PAD had substantially higher cardiovascular but lower non-cardiovascular risks than those treated in daily practice.Trial registration number: NCT02944019 (ClinicalTrials.gov Identifier).

Dysregulated pulmonary coagulation and inflammation is a hallmark of respiratory failure in various etiologies. Excessive fibrin deposition contributes to alveolar collapse, impaired gas exchange, and progression to pulmonary fibrosis. Nebulized heparin can mitigate these coagulation and inflammation disturbances. Although several randomized controlled trials have explored its effects, results remain inconsistent and limited by small patient populations. We conducted a random-effects meta-analysis to calculate the risk ratio (RR) and 95% CIs. We systematically searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for randomized controlled trials comparing nebulized unfractionated heparin to standard care or placebo in adult patients with respiratory failure either invasively mechanical ventilated or not. The primary outcome was all-cause mortality at the longest follow-up. We included randomized clinical trials enrolling adult patients with respiratory failure, comparing nebulized heparin vs. standard care or placebo, and reporting at least one clinical outcome, including all-cause mortality. Two independent investigators extracted data on trial design, setting, etiology of respiratory failure, heparin dosing regimens, follow-up duration, and outcomes. Discrepancies were resolved by consensus. We identified 16 studies (787 receiving nebulized heparin, 833 control). Six (38%) were multicenter, five focused on COVID-19, 12 enrolled ICU patients, and dosing clustered around 25,000 international units (IUs) three times a day (~75,000 IU/d for ~10 d). At the longest follow-up, nebulized heparin reduced all-cause mortality vs. control (110/645 [17.1%] vs. 157/711 [22.1%]; RR, 0.79; 95% CI, 0.66-0.95; with ten studies included). Nebulized heparin was also associated with more ventilation-free days by day 28 (mean difference, +4.85; 95% CI, 1.47-8.24). Major bleeding was rare (1.1 vs. 0.7%; RR, 1.48; 95% CI, 0.42-5.18), while no minor bleeding or heparin-induced thrombocytopenia was reported. Nebulized unfractionated heparin may improve survival in patients with respiratory failure without increasing adverse events.

Direct Oral Anticoagulant Monotherapy versus Combination Therapy with Antiplatelets in Chronic Coronary Syndrome Patients with Prior Percutaneous Coronary Intervention Requiring Anticoagulation: A Meta-Analysis.

Rivaroxaban, a factor Xa inhibitor, is used to prevent stroke in patients of atrial fibrillation (AF). This study aimed to establish a population pharmacokinetic (PPK) model for rivaroxaban using real-world data, apply it to concentration prediction, and investigate the association between drug exposure and clinical outcomes. Patients with AF receiving rivaroxaban were enrolled from an observational cohort (2016-2023) to measure plasma concentrations. An independent cohort was randomly selected to validate the PPK model. Clinical outcomes of interest included stroke or systemic thromboembolism, and major bleeding. A total of 226 patients contributed to 452 rivaroxaban concentration measurements. Rivaroxaban pharmacokinetics were adequately described using a one-compartment model with first-order elimination. The estimated apparent clearance (CL/F) and the volume of distribution (V/F) were 6.13 L/h and 45.57 L, respectively. CL/F was significantly influenced by creatinine clearance and concomitant use of cytochrome 3A4 or P-glycoprotein inhibitors, whereas V/F was associated with lean body weight. External validation demonstrated a good predictive performance at the individual level. Patients with low trough concentrations tended to have an increased risk of systemic thromboembolism, whereas those with high trough concentrations tended to have a higher risk of major bleeding. In an Asian population, rivaroxaban pharmacokinetics are influenced by renal function, lean body weight, and drug interactions. The developed PPK model facilitates the estimation of rivaroxaban concentrations at standardized timepoints from random samples. This provides a practical tool for standardized exposure assessment and the identification of patients at risk for adverse clinical outcomes. ClinicalTrials.gov identifier no. NCT05333666.