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Importance: The optimal strategy of combining left atrial appendage occlusion (LAAO) with catheter ablation (CA) in patients with atrial fibrillation (AF) during a single procedure remains unclear., Objective: To determine the effects of ablation-first vs occlusion-first strategies on long-term clinical outcomes among patients with atrial fibrillation undergoing a combined LAAO and CA procedure., Design, Setting, and Participants: The prospective, multicenter COMBINATION randomized clinical trial was conducted in 14 high-volume centers in China. Enrollment of patients with nonvalvular AF referred for the combined procedure began on July 24, 2020, and concluded on January 20, 2022., Interventions: Patients were randomly assigned to either the ablation-first group or the occlusion-first group. Outcomes of LAAO using an occlusion device and CA using a contact force-sensing catheter following different combination strategies during long-term follow-up were evaluated., Main Outcomes and Measures: The primary end point was a composite of thromboembolic events including stroke or transient ischemic attack, device-related thrombus (DRT), clinically relevant bleeding, and cardiovascular rehospitalization or death. Freedom from AF or atrial tachyarrhythmia (ATA) after a single procedure without antiarrhythmic drugs, at both 1 year and long-term follow-up, was also evaluated., Results: Of the 202 patients enrolled, 194 (96.0%) completed the trial (97 in the ablation-first group and 97 in the occlusion-first group). The mean (SD) age of the cohort was 67.3 (9.2) years, and 110 patients (56.7%) were male. All procedures achieved acute successful LAAO and restoration of sinus rhythm, with similar incidences of periprocedural complications. Compared with the ablation-first group, the occlusion-first group exhibited significantly higher event-free survival of the primary end point (83.5% vs 71.1%; hazard ratio [HR], 0.53 [95% CI, 0.29-0.95]; log-rank P = .04) during the median 2.5 (IQR, 2.3-2.8) years of follow-up. Subgroup analysis indicated that male patients and those with higher CHA2DS2-VASc scores (a composite of factors associated with stroke risk; higher scores indicate higher risk) were at lower risk of thromboembolic events. Rates of long-term freedom from AF (77.3% vs 63.5%; HR, 0.58 [95% CI, 0.34-0.97]; log-rank P = .04) and from ATA (70.1% vs 55.7%; HR, 0.62 [95% CI, 0.39-0.99]; log-rank P = .04) were higher in the occlusion-first group vs the ablation-first group. Additionally, a higher incidence of chronic peridevice leak (15 [15.5%] vs 5 [5.2%]; P = .03) and DRT (8 [8.2%] vs 1 [1.0%]; P = .04) was observed in the ablation-first group vs the occlusion-first group., Conclusions and Relevance: In this randomized clinical trial, the occlusion-first approach was superior due to its higher event-free survival of the primary end point and long-term freedom from ATA. These findings suggest that the occlusion-first approach should be recommended for combined procedures with plug-like device implantation., Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2000031486.

Atrial fibrillation (AF) is among the most prevalent forms of clinically significant arrhythmia, and stroke incidence is among the most serious AF-related complications, causing high rates of morbidity and mortality among affected patients. The European Society of Cardiology guidelines recommend a thromboembolic event risk assessment based on the CHA 2 DS 2 -VAS C score. However, stroke also occurs in some patients with a low CHA 2 DS 2 -VAS C score. Therefore, it is necessary to improve thromboembolic risk stratification in AF patients. The left atrial appendage (LAA) is considered to be the most frequent site of thrombus formation. Approximately 47% of thrombi in valvular AF and 91% of thrombi in nonvalvular AF are localized in the LAA. Therefore, identification or exclusion of LAA thrombi is critical in many clinical situations. It is essential to assess LAA morphology and function using imaging modalities (particularly echocardiography) before, during, and after interventional procedures such as AF ablation and LAA occlusion. This review article describes the anatomical, physiological, and LAA assessment in daily practice., (© 2024 Wiley Periodicals LLC.)

Aims: The CHA2DS2VASc score is recommended for stroke risk stratification in patients with atrial fibrillation (AF). This score assigns one extra point to female sex based on evidence from the early 2000s, suggesting higher thromboembolic risk in women. This incremental risk of thromboembolism in women has decreased over time between 2007 and 2018, becoming non-significant in recent years. The objective of this study was to assess the impact of removing the sex category (Sc) from the CHA2DS2VASc score, thus validating a non-sex CHA2DS2VASc (i.e. CHA2DS2VA) score., Methods and Results: We analysed UK primary and secondary care data comprising 195 719 patients with AF followed between 1998 and 2016 (mean age: 75.9 ± 12.3 years; 49.2% women). Among 126 428 non-anticoagulated patients, we compared the CHA2DS2VASc vs. CHA2DS2VA scores every calendar year. Throughout 413 007 patient-years, a total of 8742 events of ischaemic stroke or systemic embolism were recorded. Sex differences in thromboembolic risk were not observed in the lower-risk population, but higher stroke rates were consistently seen in female patients in the higher-risk category (i.e. CHA2DS2VA ≥2). C-statistics for both CHA2DS2VA and CHA2DS2VASc scores were similar over the years (ranging from 0.62 to 0.71). With CHA2DS2VA, no relevant differences were observed in integrated discrimination improvement, and net reclassification improvement (NRI) resulted in improved reclassification (11%) in lower thromboembolic risk groups. The NRI suggested misclassification in higher thromboembolic risk patients (-7%), but this did not affect their indication for anticoagulation (i.e. patients retained their high-risk status)., Conclusion: Removing Sc from the CHA2DS2VASc score does not affect its ability to discriminate thromboembolic events in the population with AF. The use of CHA2DS2VA may simplify initial decision-making for thromboprophylaxis., Competing Interests: Conflict of interest: G.Y.H.L. is a consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, and Anthos. No fees were received personally. The remaining authors have no other conflicts of interest to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Recommencement of oral anticoagulation (OAC) for patients post-intracerebral haemorrhage (ICH) remains a challenging decision for clinicians. High-quality evidence to assist with this decision is lacking and current guidelines primarily focus on balancing thromboembolic and bleeding risk., Objective: This study evaluated the literature and current guidelines for recommencement of OAC in patients who have experienced an incident ICH., Discussion: Patients with recurrent ICH while on anticoagulation therapy have associated poor outcomes. However, predicting which patients will experience recurrent ICH with OAC resumption remains challenging, and failure to resume OAC carries risks of thromboembolic events. Current data suggest that it is reasonable to resume OAC in many patients post-ICH, depending on careful consideration of individual risk factors for haemorrhagic and thromboembolic events. The application of existing risk stratification tools for thromboembolism and haemorrhage, and radiological biomarkers such as cerebral microbleeds, might also assist in decision making.

The glycoprotein IIb/IIIa antagonist tirofiban has been shown to prevent thromboembolic events during endovascular procedures, but the benefits and risks of its prophylactic early intraprocedural administration for stand-alone coil embolization of acutely ruptured aneurysms are still unclear. We conducted a retrospective single-center analysis of patients treated for aneurysmal subarachnoid hemorrhage with stand-alone coil embolization. Two study cohorts were compared according to the primary prophylactic antithrombotic medication during the procedure: patients receiving only intravenous heparin (HEP) versus patients receiving tirofiban in addition to heparin prior to final aneurysm obliteration (HEP + TF). Outcome endpoints were the incidence of angiographically visible thrombus formation or distal embolization, and the incidence of periprocedural intracranial hemorrhage (ICH). Of 204 cases, 159 were prophylactically treated with HEP and 45 with HEP + TF. Intraprocedural thromboembolic events were less frequent with HEP + TF before and after propensity score matching (PSM) (2.5% vs. 19.7%, p = 0.017). The incidence of ICH and symptomatic ICH did not differ between HEP + TF and HEP before and after PSM (20.5% vs. 30.7%, p = 0.29; and 5.1% vs. 4%, p = 0.88). Early intraprocedural tirofiban administration may be effective in preventing thromboembolic complications during stand-alone coil embolization of acutely ruptured aneurysms without increasing the risk of ICH., (© 2024. The Author(s).)

Background: The prospective, single-arm, observational, phase 4 ETNA-AF Europe study collected real-world data about safety, effectiveness and therapeutic adherence in European patients with non-valvular atrial fibrillation newly prescribed with edoxaban and followed up for 4 years., Methods: Overall, 13 164 patients were included in the full-analysis set, which means that they had at least one documentation after baseline at 4 years. The current paper reports about the 3329 Italian patients out of the whole European population., Results: In the Italian cohort, median age was 76.0 (69.0-82.0) years, with 57.4% of the patients being ≥75 years old. The CHA2DS2-VASc score was >4 in 586 (18.1%) patients. At baseline, 670 (20.8%) patients were classified as frail by the investigators. Edoxaban 30 mg/day was prescribed to 1013 (31.8%) patients: these were older, with more comorbidities and a lower estimated creatinine clearance compared with those receiving 60 mg/day. All-cause mortality was 4.1%/year and there were very low yearly rates of bleeding and thromboembolic events: major bleeding, 0.9%; intracranial hemorrhage, 0.2%; ischemic stroke, 0.3%; systemic embolism, <0.1%. These events were more frequent in patients ≥75 years or in patients with renal impairment or treated with edoxaban 30 mg/day. Advancing age was not associated with an increased incidence of intracranial bleeding., Conclusions: These findings confirm the favorable long-term safety and effectiveness profile of edoxaban in non-valvular atrial fibrillation patients treated in routine clinical care in Italy.

The HeartMate 3 (HM3) left ventricular assist device has decreased thromboembolic events and minimized the risk of pump thrombosis. However, bleeding complications due to combined antithrombotic therapy with a vitamin K antagonist (VKA) and aspirin remain high. Only limited data on the safety of VKA monotherapy in HM3 patients are available. A systematic search on the main databases was performed. Observational data and randomized trials were eligible for this analysis. As primary endpoint, we analyzed hemocompatibility-related adverse events (HRAE). As secondary endpoints, we investigated the individual components of the primary endpoint. The analysis was carried out using the odds ratio (OR) as outcome measure. A random-effects model was fitted to the data. Five manuscripts fulfilled the inclusion criteria. These trials included 785 patients (381 on VKA monotherapy, 404 on VKA and aspirin). VKA monotherapy significantly reduced HRAE (OR: 0.11 [95% confidence interval {CI}: 0.02-0.59], p = 0.01, I2 = 87%). The reduction was driven by a decrease in bleeding complications (OR: 0.12 [95% CI: 0.02-0.62], p = 0.01, I2 = 86%) without increasing the rates of thromboembolic events (OR: 0.69 [95% CI: 0.26-1.81], p = 0.45, I = 0%). Vitamin K antagonist monotherapy is associated with a significant reduction of bleeding events without increasing the risk of thromboembolic complications in HM3 patients., Competing Interests: Disclosure: T.S. received consulting/advisory fees from Medtronic Inc., Abbott Inc., BiVACOR, Berlin Heart, and CorWave; and received grant support from Medtronic Inc., Abbott Inc., Berlin Heart, and CorWave. D.W. is a proctor for Abbott Inc. and received consulting/advisory fees from Abbott Inc. and Xenios/Fresenius Medical Care. D.Z. is a proctor for and received speaker/consulting fees from Medtronic Inc., Abbott Inc., Berlin Heart, Edwards, Abiomed, and grant support from Medtronic Inc. and Abbott Inc. T.G. received speaker/consulting fees from AstraZeneca, Amgen, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, Daiichi- Sankyo, Novartis, and Pfizer, and grant support from Boehringer-Ingelheim, Bristol Myers Squibb, Medtronic and Abbott. The other authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

Background: Tranexamic acid is a recommended treatment for women with a clinical diagnosis of postpartum haemorrhage, but whether it can prevent bleeding is unclear. We conducted a systematic review and individual patient data (IPD) meta-analysis of randomised controlled trials to assess the effects of tranexamic acid in women giving birth., Methods: In this systematic review and IPD meta-analysis, we searched the WHO International Clinical Trials Registry Platform from database inception to Aug 4, 2024 for randomised trials that assessed the effects of tranexamic acid in women giving birth. Trials were eligible if they were prospectively registered, placebo-controlled, included more than 500 women, and had a low risk of bias for random sequence generation and allocation concealment. IPD were requested from the trial investigators. The primary outcomes were the numbers of women with life-threatening bleeding and thromboembolic events. We used a one-stage model to analyse the data and explored whether the effect of tranexamic acid varied by the underlying risk of life-threatening bleeding, type of birth, presence of moderate or severe anaemia, or timing of administration (before or after a diagnosis of postpartum haemorrhage). This study is registered with PROSPERO, CRD42022345775., Findings: We analysed data on 54 404 women from five trials. We obtained IPD for 43 409 women from four trials and aggregate data on 10 995 women from one trial. All trials had a low risk of bias. Life-threatening bleeding occurred in 178 (0·65%) of 27 300 women in the tranexamic acid group versus 230 (0·85%) of 27 093 women in the placebo group (pooled odds ratio [OR] 0·77 [95% CI 0·63-0·93]; p=0·008). There was no evidence that the effect of tranexamic acid varied by the underlying risk of life-threatening bleeding, type of birth, presence of moderate or severe anaemia or timing of administration. No significant difference was identified between tranexamic acid and placebo groups with regard to thromboembolic events: 50 (0·2%) of 26 571 women in the tranexamic acid group had fatal or non-fatal thromboembolic events versus 52 (0·2%) of 26 373 women in the placebo group (pooled OR 0·96 [0·65-1·41]; p=0·82) with no significant heterogeneity identified in the subgroup analyses., Interpretation: Tranexamic acid reduces the risk of life-threatening postpartum bleeding. We found no evidence that tranexamic acid increases the risk of thrombosis. Although we do not recommend the use of tranexamic acid in all women giving birth, consideration should be given to its use before a diagnosis of postpartum haemorrhage in women at high risk of death., Funding: The Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests IR and HS-S declare receipt of support from the National Institute for Health and Care Research, Wellcome, and the John Moulton Foundation for support of their other research activities into the effects of tranexamic acid. All payments were made to their employing institution (London School of Hygiene & Tropical Medicine). IR also declares an unpaid role as convenor of an ad-hoc group (The Joint Royal Colleges tranexamic acid in surgery implementation group) to increase the use of tranexamic acid in surgical patients as per National Institute for Health and Care Excellence guidance. LS reports receipt of payment or honoraria from Ferring Pharmaceuticals, Norgine, Bayer, Pfizer, GlaxoSmithKline, and Organon for lectures, presentations, speakers bureaus, manuscript writing, or educational events. HA declares receipt of support from the National Institute of Child Health and Human Development/National Institutes of Health for grant OPTIMUM OB-TXA: Optimal TIMing, route and dose of tranexamic acid prior to UMbilical cord clamp for postpartum haemorrhage prevention; consulting fees from Hemosonics, Coagulant Therapeutics, Hemosquid; and payment or honoraria from COR2ED for lectures, presentations, speakers bureaus, manuscript writing, or educational events. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

New-onset atrial fibrillation (AF) occurring during acute medical illness or post-operatively has long been considered a benign phenomenon, and its recurrence risk was deemed low. However, recent data suggest a high risk of AF recurrence, and a thromboembolic risk similar to the risk associated with AF occurring without a provoking factor. As we lack interventional data, there are currently no guidelines on the long-term management of new-onset AF occurring during an acute medical condition. This paper aims to review current knowledge on epidemiology, recurrence risk, thromboembolic risk and anticoagulation strategies in the setting of new-onset AF occurring transiently with acute stress., Competing Interests: les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Direct current (DC) cardioversion is an everyday clinical procedure used to restore sinus rhythm from atrial fibrillation. This review summarises the current state of art in Denmark. Sufficient anticoagulation must be ensured before DC cardioversion to reduce the risk of thromboembolism. Biphasic maximum energy shocks delivered via anterolateral electrodes are recommended. Overall success is high, and the complication rate is low. Relapse of atrial fibrillation is common, and a long-term treatment strategy which may include antiarrhythmics, ablation and lifestyle change should be established in collaboration with the patient., (Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/.)

Surgical occlusion of the left atrial appendage (LAA) during cardiac surgery in patients with atrial fibrillation (AF) is known to reduce thromboembolism. However, data on the clinical significance of LAA occlusion (LAAO) in patients with mitral regurgitation (MR) are lacking. A total of 237 AF patients with chronic severe MR who underwent mitral valve (MV) surgery were retrospectively analyzed. Patients were divided into two groups according to concomitant LAAO or LAA preservation. The primary outcome was a composite of all-cause death and thromboembolic events (ischemic stroke or systemic embolism). The LAA was surgically occluded in 98 (41%) patients and preserved in 139 (59%) patients. During the follow-up period (median, 37 months), 29 primary outcomes occurred. In the Kaplan-Meyer analysis, the LAA preservation group showed a greater cumulative incidence of the primary outcome (P = 0.002) and thromboembolic events (P = 0.003) than the LAAO group. In the univariate Cox regression analysis, coronary artery disease, CHA 2 DS 2 -VASc score, a cauliflower-shaped LAA, Maze, and no LAAO were significantly associated with the primary outcome. In the multivariate Cox regression analysis, concomitant LAAO was significantly linked to the primary outcome (hazard ratio [HR]: 0.30, 95% confidence interval [CI]: 0.10-0.91, P = 0.033) and thromboembolic events (HR: 0.19, 95% CI: 0.04-0.87, P = 0.032). These benefits from LAAO were consistent, even after propensity score-matched analysis. For patients undergoing surgery for chronic MR who also have AF, concomitant surgical LAAO is associated with favorable clinical outcome., (© 2024. The Author(s).)

Introduction: The transition to or from direct oral anticoagulants (DOACs) is common in clinical practice., Areas Covered: A literature search was conducted on PubMed, Google Scholar, and UpToDate up to March 2024 for conditions and approaches for transitioning from one agent to the other. No randomized clinical trials were retrieved except for two studies regarding switching to DOAC in well-conducted vitamin K antagonist (VKA) therapy. A narrative review was conducted addressing the conditions for switching from one agent to the other, such as thromboembolic events and major bleeding during anticoagulation, development or worsening of kidney or liver failure, initiation of interfering drugs, adverse events such as allergic reactions, frailty, patients' preferences, and affordability. During transitions from one anticoagulant to the other, the risk of both thromboembolic and bleeding complications should be minimized. The current approaches for such transitions are derived from those employed in clinical trials evaluating DOAC and from product information., Expert Opinion: Many uncertainties remain regarding those circumstances requiring a change in anticoagulant strategies, as they lack evidence-based guidance. It can be envisaged that the problem of switching to and from DOAC will need additional studies especially addressing the conditions and the best approach to such transitions.

Background: Patients with an indication for oral anticoagulation who undergo percutaneous coronary intervention require a combination of oral anticoagulation and antiplatelet therapy. The use of a coronary stent with a thromboresistant and pro-healing coating may allow an abbreviated duration of dual antiplatelet therapy (DAPT) without an increase in the risk of thromboembolic events., Methods: Patients with an indication for oral anticoagulation undergoing percutaneous coronary intervention were randomized to treatment with the COBRA polyzene F (PzF) stent followed by 14 days of DAPT or a Food and Drug Administration-approved new-generation drug-eluting stent followed by 3 or 6 months of DAPT. The bleeding coprimary end point was Bleeding Academic Research Consortium type ≥2 beyond 14 days (or after hospital discharge) until 6 months. The thromboembolic coprimary end point was the composite of all-cause death, myocardial infarction, definite or probable stent thrombosis, or ischemic stroke at 6 months. The trial hypothesis was that the COBRA PzF stent strategy would be superior with respect to bleeding events and noninferior with respect to thromboembolic events., Results: A total of 996 patients underwent randomization. The bleeding end point occurred in 37 of 475 patients (7.8%) in the COBRA PzF group and 47 of 482 patients (9.8%) in the control group (difference, -2.0 [95% CI, -5.6 to 1.6]; P =0.14). The thromboembolic end point occurred in 37 of 492 patients (7.5%) in the COBRA PzF group and 24 of 490 patients (4.9%) in the control group (difference, 2.6%; prespecified noninferiority margin 5%, upper limit of 1-sided 95% CI of the difference, 5.2%; P noninferiority =0.07)., Conclusions: In patients with an indication for oral anticoagulation undergoing percutaneous coronary intervention, treatment with the COBRA PzF stent plus 14 days of DAPT was not superior with respect to bleeding events and was not noninferior with respect to thromboembolic events at 6 months compared with treatment with standard Food and Drug Administration-approved drug-eluting stent plus 3 to 6 months of DAPT., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02594501., Competing Interests: Dr Byrne reports research or educational funding to the institution of current employment from Abbott Vascular, Biosensors, Boston Scientific, and Translumina. Dr Maeng is supported by a grant from the Novo Nordisk Foundation (grant number NNF22OC0074083), has received lecture and advisory board fees from Astra-Zeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, and Novo Nordisk, has received research grants from Philips, Bayer, and Novo Nordisk, has ongoing research contracts with Novo Nordisk and Philips, and is a minor shareholder in Eli Lilly and Novo Nordisk. Dr Brunner is a previous employee of CeloNova. Dr Urban reports personal consulting fees from and is a shareholder of MedAlliance, Nyon, Switzerland, outside of the submitted work. Dr Cutlip reports contracted research support paid to institution of current employment from Celonova. Dr Kirtane reports Institutional funding to Columbia University and/or Cardiovascular Research Foundation from Medtronic, Boston Scientific, Abbott Vascular, Amgen, CathWorks, Cardiovascular Systems Inc, Philips, ReCor Medical, Neurotronic, Biotronik, Chiesi, Bolt Medical, Magenta Medical, Canon, SoniVie, and Shockwave Medical. In addition to research grants, institutional funding includes fees paid to Columbia University and/or Cardiovascular Research Foundation for consulting and/or speaking engagements in which Dr Kirtane controlled the content. Personal: Travel Expenses/Meals from Amgen, Medtronic, Biotronik, Boston Scientific, Abbott Vascular, CathWorks, Edwards, Cardiovascular Systems Inc, Novartis, Philips, Abiomed, ReCor Medical, Chiesi, Zoll, Shockwave, and Regeneron. The other authors report no conflicts.

Background: Vitamin-K antagonists (VKAs) have widely been replaced by non-VKA oral anticoagulants (NOACs). This includes Austria, Germany and Switzerland, where as VKA, instead of warfarin, the much longer-acting phenprocoumon is used, which was not compared to NOACs in clinical trials., Methods: Using administrative data from a large German health insurance, we included all anticoagulation-naïve patients with a first prescription of a NOAC or VKA between 2012 and 2020. We analysed overall survival, major adverse cardiac and cerebrovascular events, major thromboembolic events and major bleeding., Results: Overall, 570,137 patients were included (apixaban: 26.9%, dabigatran: 4.6%, edoxaban: 8.8%, rivaroxaban: 39.1% and VKA: 20.7% of these 99.4% phenprocoumon). In the primary analysis using a 1:1 propensity score matching-cohort (PSM-cohort), a significantly higher overall mortality was found for apixaban, edoxaban and rivaroxaban (all p < 0.001) but not for dabigatran (p = 0.13) compared to VKA. In this PSM-cohort, 5-year mortality was 22.7% for apixaban versus 12.7% for VKA, 19.5% for edoxaban versus 11.4% for VKA, 16.0% for rivaroxaban versus 12.3% for VKA (all p < 0.001) and 13.0% for dabigatran versus 12.8% for VKA (p = 0.06). The observed effect was confirmed in sensitivity analyses using un-weighted and three different weighted Fine-Gray regression models on the basis of the entire cohort., Conclusions: In this large real-world analysis, apixaban, edoxaban and rivaroxaban, but not dabigatran, were associated with worse survival compared to VKA. These findings, consistent with a few other studies including phenprocoumon, cast profound doubts on the unreflected, general use of NOACs. Randomized trials should assess whether phenprocoumon might actually be superior to NOACs., (© 2024 BARMER Institut für Gesundheitssystemforschung and The Author(s). Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Background: Interventional left atrial appendage occlusion (LAAO) mitigates the risk of thromboembolic events in nonvalvular atrial fibrillation (AF) patients with contraindication for long-term oral anticoagulation (OAC). Patients with prior stroke have a relevantly increased risk of recurrent stroke, so the effectiveness of LAAO could be reduced in this specific very high-risk patient group., Aim: This sub-study of the LAARGE registry investigates the effectiveness and safety of LAAO for secondary prevention in nonvalvular AF patients with a history of stroke., Methods: LAARGE is a prospective, non-randomised registry on the clinical reality of LAAO. The current sub-study employs data from index procedure and 1-year follow-up. Effectiveness and safety were assessed by documentation of all-cause mortality, non-fatal thromboembolism, procedure-related complications, and bleeding events., Results: A total of 638 patients were consecutively included from 38 hospitals in Germany and divided into two groups: 137 patients with a history of stroke (21.5%) and 501 patients without. Successful implantation was consistent between both groups (98.5% vs. 97.4%, p = NS), while peri-procedural MACCE and other complications were rare (0% vs. 0.6% and 4.4% vs. 4.0%, respectively; each p = NS). Kaplan-Meier estimate showed no significant difference in primary effectiveness outcome measure (freedom from all-cause death or non-fatal stroke) between both groups at follow-up (87.8% vs. 87.7%, p = NS). The incidence of transient ischemic attack or systemic embolism at follow-up was low (0% vs. 0.5% and 0.9% vs. 0%, respectively; each p = NS). Severe bleeding events after hospital discharge were rare (0% vs. 0.7%, p = NS)., Conclusions: Patients with prior stroke demonstrated similar effectiveness and safety profile for LAAO as compared to patients without prior stroke. LAAO could serve as a feasible alternative to OAC for secondary stroke prevention in this selected group of nonvalvular AF patients., Gov Identifier: NCT02230748., (© 2024. The Author(s).)

Anticoagulants have long been fundamental in preventing and treating thromboembolic disorders, with a recent shift of focus towards direct oral anticoagulants, thanks to their ease of use, efficacy, and safety. Despite these advancements, bleeding complications remain a major concern with any anticoagulant, highlighting the need for safer drugs. Factor XI (FXI) inhibitors have emerged as promising agents in this regard, offering a novel approach by targeting upstream factors in the coagulation system. Phase II trials have shown encouraging outcomes, indicating a reduced bleeding risk compared to that associated with traditional anticoagulants, particularly in the context of cardiovascular disease management when combined with antiplatelet therapy. However, the variability in findings and limited efficacy data call for a cautious interpretation pending insights from phase III trials. These trials are essential for validating the potential of FXI inhibitors to balance bleeding risk reduction and maintain anticoagulant efficacy. This review explores the pharmacology, potential indications, clinical data, and future directions of FXI inhibitors, providing a perspective on their evolving role in anticoagulant therapy. It also provides a detailed analysis of data from published clinical trials on FXI inhibitors in various indications. Preliminary data from ongoing trials are also outlined. As the field moves forward, a cautiously optimistic outlook can be expected, focusing on comprehensive data from phase III trials to define the role of FXI inhibitors in various clinical scenarios.

Objective: To evaluate whether treatment with erythropoiesis-stimulating agents (ESAs) for chemotherapy-induced anemia affects progression-free survival (PFS) in patients receiving front-line chemotherapy following surgery for ovarian cancer (OC)., Methods: We retrospectively reviewed all consecutive patients who received front-line chemotherapy after surgery between 2013 and 2019 at six institutions. The patients were divided according to the use of ESAs during front-line chemotherapy. The primary endpoint was PFS. The secondary endpoint was the occurrence of thromboembolism. Propensity score matching (PSM) analysis was used to compare survival between matched cohorts., Results: Overall, 2147 patients (433 receiving ESA and 1714 for no-ESA) were identified, with a median follow-up of 44.0 months. The ESA group showed a significantly higher proportion of stage III/IV disease (81.8% vs 61.1%; P < 0.001) and postoperative gross residual disease (32.3% vs 21.2%; P < 0.001) than the no-ESA group. In the multivariable Cox regression analysis, the use of ESAs did not affect PFS (adjusted hazard ratio, 1.03; 95% confidence interval [CI]: 0.89-1.20; P = 0.661). The incidence of thromboembolism was 10.2% in the ESA group and 4.6% in the no-ESA group (adjusted odds ratio, 6.58; 95% CI: 3.26-13.28; P < 0.001). When comparing the well-matched cohorts after PSM, PFS did not differ between the ESA (median PFS 23.5 months) and no-ESA groups (median PFS 22.2 months) (P = 0.540, log-rank test)., Conclusions: The use of ESAs during front-line chemotherapy did not negatively affect PFS in patients with OC after surgery but increased the risk of thromboembolism., (© 2024 International Federation of Gynecology and Obstetrics.)

Background: It is uncertain whether prothrombin complex concentrate (PCC) improves hemostasis in patients on treatment with oral factor Xa-inhibitors (XaI) who require emergency surgery., Objectives: To evaluate whether, in patients with therapeutic levels of oral XaI, preoperative PCC prevents excessive bleeding during and after emergency surgery and is not associated with thrombotic complications., Methods: We conducted a prospective cohort study wherein a fixed 2000 IU dose of 4-factor PCC was given to patients taking oral XaI with plasma XaI levels of at least 75 ng/mL before the emergency surgery with an expected blood loss of at least 50 mL. Patients were followed for 30 days. The primary efficacy outcome was the incidence of normal or mildly abnormal surgical hemostasis, as assessed by the surgeon; primary safety outcome was the incidence of thromboembolic events within 7 days., Results: We included 20 patients, of which 50% were female, on apixaban (75%) or rivaroxaban (25%) with median XaI level of 128 ng/mL (range, 77-497 ng/mL). The median duration of surgery was 2 hours 42 minutes (range, 15 minutes to 8 hours 17 minutes). Normal or mildly abnormal hemostasis was observed in 16 patients (80%); 2 patients had moderately abnormal and 2 had severely abnormal hemostasis, 1 each of those was considered due to local or technical factors. There were 4 deaths (20%) secondary to underlying disease and 1 incidental pulmonary embolism in a patient with cancer., Conclusion: A fixed dose of PCC appears to control hemostasis in patients with therapeutic plasma levels of apixaban or rivaroxaban requiring emergency surgery., Competing Interests: Declaration of competing interests S.S. served on data safety monitoring boards for Alexion, Bayer, Boehringer-Ingelheim, Regeneron, and Sanofi; served on a steering committee for Octapharma; served on event adjudication for Daiichi Sankyo and Takeda. V.B. received honorarium from Bayer. F.G.’s institution received research funding from Novo Nordisk, Roche, Takeda, Bayer, Pfizer, BioMarin, and CSL. R.I. received honoraria for advisory boards for Aspen, LeoPharma, Sanofi, and Inari. P.L.G. is named on a patent, “Novel methods to measure protease inhibitors.” N.C., A.I., S.M., and J.I.W. have no relevant conflicts., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Inhibiting the coagulation factor XI (FXI) is a novel strategy for prevention and treatment of thromboembolism without affecting extrinsic coagulation pathways. SHR-2004 is a humanized monoclonal antibody that selectively binds to FXI and factor XIa (FXIa)., Research Design & Methods: This randomized, double-blind, dose-escalation, placebo-controlled study evaluated SHR-2004 administered either intravenously (i.v.; Part A) or subcutaneously (s.c.; Part B). In Part A, 24 subjects received a single i.v. dose of SHR-2004 (0.1, 0.3, or 1.0 mg/kg) or placebo. In Part B, 40 subjects received a single s.c. dose of SHR-2004 (0.5, 1.0, 3.0, or 4.5 mg/kg) or placebo., Results: SHR-2004 was well tolerated. Plasma exposure to SHR-2004 increased in a dose-dependent manner. The geometric mean half-time ranged from 11.6 to 13.0 days. FXI activity decreased, and the activated partial thromboplastin time (APTT) was prolonged after i.v. and s.c. administration in a dose- and time-dependent manner. FXI activity was nearly completely abolished immediately after administering the highest i.v. dose, with the average APTT prolonged to nearly three times of baseline., Conclusion: SHR-2004 is a promising candidate for further development as an anticoagulant drug that exerts effective anticoagulation with minimal risk of bleeding., Clinical Trial Registration: www.clinicaltrials.gov identifier is NCT05369767.

Background: Thromboembolic complications are one of the major periprocedural complications following neuroendovascular procedures. Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel remain the principal agents for prevention of thromboembolic complications. However, clopidogrel resistance is associated with higher risk of thromboembolic complications. This study investigated the safety and efficacy of DAPT with ticagrelor and aspirin in patients undergoing intracranial stenting procedures., Methods: This retrospective study was based on patients with intracranial aneurysms who undergoing intracranial stenting procedures at our institution between August 2017 and July 2020. These patients received DAPT with ticagrelor and aspirin were included. DAPT with 90 mg ticagrelor twice daily and aspirin 100 mg daily was continued for 3 months after the intracranial stenting procedure and aspirin continued for 1 year., Results: In this study, 151 patients were identified. The most common aneurysm location was the internal carotid artery with 127 (71.8%) patients. Of the 151 cases with 160 treated aneurysms, 30 (18.8%) patients were treated by flow diverters (FDs), and 130 (81.2%) by stent-assisted coiling. Five (3.3%) patients had thromboembolic complications. Intraprocedural aneurysmal rupture was observed in one patient because of coil extrusion during coil insertion. None of the patients showed a newly DAPT-related intracerebral hemorrhage. Two patients developed dyspnea, and the symptom resolved without intervention. Furthermore, ecchymoma and gastrointestinal bleeding occurred in one patient respectively. DAPT-related thromboembolic and hemorrhagic complications were not significantly different between the FD group and stent-assisted coiling group., Conclusions: In our study, DAPT combining ticagrelor and aspirin seems to be a safe and efficient treatment for preventing thromboembolic complications in patients with intracranial aneurysms, without any increase in hemorrhagic complications. Ticagrelor may be an effective alternative for patients undergoing neurointervention.

Background and Aims: The role of gender in decision-making for oral anticoagulation in patients with atrial fibrillation (AF) remains controversial., Methods: The population cohort study used electronic healthcare records of 16 587 749 patients from UK primary care (2005-2020). Primary (composite of all-cause mortality, ischaemic stroke, or arterial thromboembolism) and secondary outcomes were analysed using Cox hazard ratios (HR), adjusted for age, socioeconomic status, and comorbidities., Results: 78 852 patients were included with AF, aged 40-75 years, no prior stroke, and no prescription of oral anticoagulants. 28 590 (36.3%) were women, and 50 262 (63.7%) men. Median age was 65.7 years (interquartile range 58.5-70.9), with women being older and having other differences in comorbidities. During a total follow-up of 431 086 patient-years, women had a lower adjusted primary outcome rate with HR 0.89 vs. men (95% confidence interval [CI] 0.87-0.92; P < .001) and HR 0.87 after censoring for oral anticoagulation (95% CI 0.83-0.91; P < .001). This was driven by lower mortality in women (HR 0.86, 95% CI 0.83-0.89; P < .001). No difference was identified between women and men for the secondary outcomes of ischaemic stroke or arterial thromboembolism (adjusted HR 1.00, 95% CI 0.94-1.07; P = .87), any stroke or any thromboembolism (adjusted HR 1.02, 95% CI 0.96-1.07; P = .58), and incident vascular dementia (adjusted HR 1.13, 95% CI 0.97-1.32; P = .11). Clinical risk scores were only modest predictors of outcomes, with CHA2DS2-VA (ignoring gender) superior to CHA2DS2-VASc for primary outcomes in this population (receiver operating characteristic curve area 0.651 vs. 0.639; P < .001) and no interaction with gender (P = .45)., Conclusions: Removal of gender from clinical risk scoring could simplify the approach to which patients with AF should be offered oral anticoagulation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Rationale: Thromboembolism is a serious complication of endovascular treatment for ruptured cerebral aneurysms. The administration of antiplatelet agents before endovascular treatment for ruptured cerebral aneurysms may reduce the risk of thromboembolic complications., Aim: This study aimed to assess the safety and efficacy of preoperative aspirin administration in endovascular treatment for ruptured cerebral aneurysms., Sample Size Estimates: Assuming a 15% incidence rate of both intraoperative thromboembolic morbidity and symptomatic ischemic lesions on magnetic resonance imaging diffusion-weighted imaging scans assessed by an Independent Review Committee, a sample size of 484 will be required to detect a 10% improvement with aspirin administration with 90% power using the Pearson's chi-square test at a two-sided significance level of 2.5% for each primary outcome, after accounting for a 5% dropout rate., Methods and Design: ASTOP is a multicenter, randomized, double-blind, placebo-controlled clinical trial. A total of 484 patients with ruptured cerebral aneurysms receiving coil embolization within 72 h of onset will be randomly assigned 1:1 to receive 200 mg of aspirin or placebo before the procedure., Study Outcomes: The primary outcomes will be the incidence rates of intraoperative thromboembolic complications and symptomatic ischemic lesions on magnetic resonance imaging diffusion-weighted imaging scans evaluated by the Independent Review Committee. The secondary outcomes will be the incidence rate of cerebral ischemic events and all bleeding events within 14 days of enrollment and functional outcomes defined by the modified Rankin Scale score at 90 days., Discussion: This trial will provide valuable data on the role of antiplatelet agents during endovascular treatment for ruptured cerebral aneurysms., Trial Registration: Registration: Japan Registry of Clinical Trials, Identifier: jRCTs031210421., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hirai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: Continuous, therapeutic anticoagulation is the standard of care for patients on extracorporeal membrane oxygenation (ECMO). The risks of hemorrhage exacerbated by anticoagulation must be weighed with the thrombotic risks associated with ECMO. We hypothesized increased thrombotic events in patients who had interrupted (vs. continuous) anticoagulation during venovenous ECMO., Design: This is a retrospective, observational study., Setting: Enrollment of individuals took place at three adult ECMO centers in Minnesota from 2013 to 2022., Patients: This study consists of 346 patients supported with venovenous ECMO., Interventions: Anticoagulation administration was collected from electronic health records, including frequency and duration of anticoagulation interruptions (IAs) and timing and type of thrombotic events, and data were analyzed using descriptive statistics., Measurements and Main Results: A total of 156 patients had IA during their ECMO run and 190 had continuous anticoagulation. Risk adjusted logistic regression demonstrated that individuals in the IA group were not statistically more likely to experience a thrombotic complication (odds ratio [OR], 0.69; 95% CI, 0.27-1.70) or require ECMO circuit change (OR, 1.36; 95% CI, 0.52-3.49). Subgroup analysis demonstrated greater frequency of overall thrombotic events with increasing frequency and duration of anticoagulation being interrupted (p = 0.001)., Conclusions: Our multicenter analysis found a similar frequency of thrombotic events in patients on ECMO when anticoagulation was interrupted vs. administered continuously. Further investigation into the impact of the frequency and duration of these interruptions is warranted., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Introduction: Several randomised controlled trials have demonstrated that novel oral anticoagulants are safer compared with vitamin K antagonists for the management of non-valvular atrial fibrillation (NVAF) to prevent thromboembolic events in the general population. There is a growing interest in the use of apixaban in patients with end-stage renal disease (ESRD) undergoing peritoneal dialysis (PD) but there is a lack of randomised data in this population., Methods and Analysis: APIDP2 is a prospective parallel, randomised, open-label, blinded endpoint trial involving patients with ESRD undergoing chronic PD who have NVAF. A total of 178 participants will be recruited from 20 French PD centres. Eligible patients will be randomly assigned to receive either apixaban at a reduced dose of 2.5 mg two times per day (dose determined with the previous pharmacokinetic study APIDP1) or dose-adjusted to international normalised ratio (INR) target (2-3) coumadin therapy. Anticoagulation to prevent thromboembolic events will be initiated or changed according to the randomisation for a duration of 1 year. The primary outcome is a major or clinically relevant non-major bleeding from randomisation up to month 12, assessed according to the International Society on Thrombosis and Haemostasis Score. Secondary outcomes encompass an efficacy composite criterion combining stroke or transient ischaemic attack (TIA), cardiovascular death and thrombosis including myocardial infarction cumulated at 12 months. Bleeding events will be also classified according to Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) and Thrombolysis In Myocardial Infarction (TIMI) criteria and pharmacodynamics outcomes will evaluate the time within the INR target range of 2-3 in the warfarin arm over 1 year, and anti-Xa apixaban activity in case of bleeding events and at 1 month, 6 months and 12 months of follow-up in the apixaban arm. To demonstrate that apixaban is safer than warfarin at 1 year, assuming two interim analyses after 60 and 118 patients, a bilateral alpha risk of 5% and a power of 80%, 178 patients are needed in this randomised trial (effect size found from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Study among patients with creatinine clearance 25-30 ml/min), that is, 89 patients per group., Ethics and Dissemination: The study has been approved by the ethics committee Comité de Protection des Personnes Sud Est III - Lyon - FRANCE, CT number 2023-507544-37-00. Written informed consent is required for each participant. Findings will be presented at scientific meetings and published in peer-reviewed journals., Trial Registration: ClinicalTrials.gov, NCT06045858; European Clinical Trial System, CT number 2023-507544-37-00., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: COVID-19 triggers prothrombotic and proinflammatory changes, with thrombotic disease prevalent in up to 30% SARS-CoV-2 infected patients. Early work suggests that aspirin could prevent COVID-19 related thromboembolic disorders in some studies but not others. This study leverages data from the largest integrated healthcare system in the United States to better understand this association. Our objective was to evaluate the incidence and risk of COVID-19 associated acute thromboembolic disorders and the potential impact of aspirin., Methods: This retrospective, observational study utilized national electronic health record data from the Veterans Health Administration. 334,374 Veterans who tested positive for COVID-19 from March 2, 2020, to June 13, 2022, were included, 81,830 of whom had preexisting aspirin prescription prior to their COVID-19 diagnosis. Patients with and without aspirin prescriptions were matched and the odds of post-COVID acute thromboembolic disorders were assessed., Results: 10.1% of Veterans had a documented thromboembolic disorder within 12 months following their COVID-19 diagnosis. Those with specific comorbidities were at greatest risk. Preexisting aspirin prescription was associated with a significant decrease risk of post-COVID-19 thromboembolic disorders, including pulmonary embolism (OR [95% CI]: 0.69 [0.65, 0.74]) and deep vein thrombosis (OR [95% CI]: 0.76 [0.69, 0.83], but an increased risk of acute arterial diseases, including ischemic stroke (OR [95% CI]: 1.54 [1.46, 1.60]) and acute ischemic heart disease (1.33 [1.26, 1.39])., Conclusions: Findings demonstrated that preexisting aspirin prescription prior to COVID-19 diagnosis was associated with significantly decreased risk of venous thromboembolism and pulmonary embolism but increased risk of acute arterial disease. The risk of arterial disease may be associated with increased COVID-19 prothrombotic effects superimposed on preexisting chronic cardiovascular disease for which aspirin was already prescribed. Prospective clinical trials may help to further assess the efficacy of aspirin use prior to COVID-19 diagnosis for the prevention of post-COVID-19 thromboembolic disorders., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Orthopaedic and sports medicine clinicians can improve outcomes for transgender patients by understanding the physiological effects of gender-affirming hormone therapy (GAHT). This narrative review investigated the role of GAHT on bone mineral density, fracture risk, thromboembolic risk, cardiovascular health and ligament/tendon injury in this population. A search from the PubMed database using relevant terms was performed. Studies were included if they were levels 1-3 evidence. Due to the paucity of studies on ligament and tendon injury risk in transgender patients, levels 1-3 evidence on the effects of sex hormones in cisgender patients as well as basic science studies were included for these two topics. This review found that transgender patients on GAHT have an elevated fracture risk, but GAHT has beneficial effects on bone mineral density in transgender women. Transgender women on GAHT also have an increased risk of venous thromboembolism, stroke and myocardial infarction compared with cisgender women. Despite these elevated risks, studies have found it is safe to continue GAHT perioperatively for both transgender women and men undergoing low-risk operations. Orthopaedic and sports medicine clinicians should understand these unique health considerations for equitable patient care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia, and its presentation differs according to age and sex. Recent studies have revealed differences in AF among various demographic groups, including the Latin American population., Objectives: To better understand potential disparities in AF prevalence and treatment strategies in the Brazilian population through data from a large multicentric prospective registry., Methods: The Rede D'Or AF registry is a multicenter prospective observational study including patients aged ≥ 18 years with AF who were seen in the emergency department of 32 tertiary hospitals in Brazil. Patients were characterized according to sex and other baseline characteristics and were classified according to previous anticoagulant use. The lack of anticoagulant use in patients with previous indications was analyzed. Statistical significance was set at 5%., Results: The study data were from a total of 1955 patients enrolled. Male sex was more prevalent, and men were younger than the women. Due to an increased prevalence of previous AF episode and a higher CHA2DS2-VASc score, more women had indications for anticoagulant therapy; however, a significant proportion was not receiving this treatment. From 29 in-hospital deaths, 15 patients had previous indication for anticoagulation, but only 3 were using anticoagulants., Conclusion: This study revealed sex-related differences in the Brazilian population of patients with AF that are consistent with trends in high-income countries. The promotion of better implementation of anticoagulant and antithrombotic therapies to reduce the risk of death and thromboembolic events among women with AF in Brazil is crucial.

Introduction: Heparin, a commonly used anticoagulant in cardiac surgery, binds to antithrombin III (ATIII) to prevent clot formation. However, heparin resistance (HR) can complicate surgical procedures, leading to increased thromboembolic risks and bleeding complications. Proper diagnosis and management of HR are essential for optimizing surgical outcomes., Methodology: Diagnosis of HR involves assessing activated clotting time (ACT) and HR assays. Management strategies were identified through a comprehensive review of the literature, including studies exploring heparin dosage adjustments, antithrombin supplementation, and alternative anticoagulants in cardiac surgery patients with HR. A thorough search of relevant studies on HR was conducted using multiple scholarly databases and relevant keywords, resulting in 59 studies that met the inclusion criteria., Discussion: HR occurs when patients do not respond adequately to heparin therapy, requiring higher doses or alternative anticoagulants. Mechanisms of HR include AT III deficiency, PF4 interference, and accelerated heparin clearance. Diagnosis involves assessing ACT and HR assays. HR in cardiac surgery can lead to thromboembolic events, increased bleeding, prolonged hospital stays, and elevated healthcare costs. Management strategies include adjusting heparin dosage, supplementing antithrombin levels, and considering alternative anticoagulants. Multidisciplinary management of HR involves collaboration among various specialities. Strategies include additional heparin doses, fresh frozen plasma (FFP) administration, and antithrombin concentrate supplementation. Emerging alternatives to heparin, such as direct thrombin inhibitors and nafamostat mesilate, are also being explored., Conclusion: Optimizing the management of HR is crucial for improving surgical outcomes and reducing complications in cardiac surgery patients. Multidisciplinary approaches and emerging anticoagulation strategies hold promise for addressing this challenge effectively., (© The Author(s), published by EDP Sciences, 2024.)

The management of patients with atrial fibrillation (AF) requires intricate clinical decision-making to optimize outcomes. In everyday clinical practice, physicians undergo difficult choices to better manage patients with AF. They need to balance thromboembolic and bleeding risk to focus on patients' symptoms and to manage a variety of multiple comorbidities. In this review, we aimed to explore the multifaceted dimensions of clinical decision-making in AF patients, encompassing the definition and diagnosis of clinical AF, stroke risk stratification, oral anticoagulant therapy selection, consideration of bleeding risk, and the ongoing debate between rhythm and rate control strategies. We will also focus on possible grey zones for the management of AF patients. In navigating this intricate landscape, clinicians must reconcile the dynamic interplay of patient-specific factors, evolving guidelines, and emerging therapies. The review underscores the need for personalized, evidence-based clinical decision-making to tailor interventions for optimal outcomes according to specific AF patient profiles.

Background: Although anticoagulants may potentially increase the risk of post-colonoscopy bleeding events, temporary discontinuation of medications could elevate the risk of thromboembolism (TE). There is a paucity of data regarding the incidence of bleeding and TE events in patients undergoing colonoscopy while on uninterrupted or interrupted anticoagulant therapy. Therefore, we aimed to ascertain the risks of post-colonoscopy TE and bleeding in patients with continuous or interrupted use of anticoagulant agents., Methods: The electronic databases of PubMed, Embase, and the Cochrane library were comprehensively searched from inception to March 15, 2024. We identified studies reporting the incidence of bleeding and TE events in patients undergoing colonoscopy with uninterrupted or interrupted anticoagulant therapy. The pooled incidence rate of bleeding and TE events was estimated using a random-effects model., Results: This study included a total of 15 studies involving 63, 017 patients. Overall, the incidence of post-procedural bleeding for uninterrupted and interrupted direct oral anticoagulants (DOACs) was found to be 3.60 % (95 % CI: 1.60 %-5.60 %), and 0.90 % (95 % CI: 0.10 %-10.30 %), respectively. Subgroup analysis revealed that older age patients (≥65 years) had a significantly higher rate of bleeding with uninterrupted DOACs therapy compared to younger age patients (< 65 years) (7.20 % vs. 2.00 %). The highest rate of bleeding was observed in Asia (7.20 %, 95 % CI: 2.20 %-12.10 %). Similarly, the risk of bleeding was significantly increased among patients interrupting DOACs therapy in Asia compared to North America (1.40 % vs. 0.26 %). For patients on uninterrupted and interrupted warfarin, a higher rate of bleeding events was observed in older age patients than younger age patients (4.90 % vs. 0.80 %, and 2.20 % vs. 1.70 %, respectively). Uninterrupted warfarin showed a more significant risk of bleeding in Asia (4.20 %, 95%CI: 1.90 %-6.60 %) compared to North America (1.00 %, 95%CI: 0.50 %-1.50 %). Among those who did not interrupt DOACs therapy, the incidence of TE was the lowest (0.08 %, 95%CI: 0.04 %-0.11 %)., Conclusion: This study provides a comprehensive assessment of bleeding and TE risks in patients undergoing colonoscopy while receiving uninterrupted or interrupted anticoagulant therapy in the real-world setting. The overall incidence of post-colonoscopy bleeding and TE events is relatively low. However, the uninterrupted DOACs and warfarin are associated with an elevated risk of bleeding, particularly among elderly patients and the Asian population., Competing Interests: Declaration of competing interest All the authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Patients receiving left ventricular assist device (LVAD) support require long-term anticoagulation to reduce the risk of thromboembolic complications. Apixaban is a direct oral anticoagulant that has become first-line therapy; however, its safety in LVAD recipients has not been well described., Objectives: This study sought to investigate whether, in patients with a fully magnetically levitated LVAD, treatment with apixaban would be feasible and comparable with respect to safety and freedom from the primary composite outcome of death or major hemocompatibility-related adverse events (HRAEs) (stroke, device thrombosis, major bleeding, aortic root thrombus, and arterial non-central nervous system thromboembolism) as compared with treatment with warfarin., Methods: The DOAC LVAD (Evaluation of the Hemocompatibility of the Direct Oral Anti-Coagulant Apixaban in Left Ventricular Assist Devices) trial was a phase 2, open label trial of LVAD recipients randomized 1:1 to either apixaban 5 mg twice daily or warfarin therapy. All patients were required to take low-dose aspirin. Patients were followed up for 24 weeks to evaluate the primary composite outcome., Results: A total of 30 patients were randomized: 14 patients to warfarin and 16 patients to apixaban. The median patient age was 60 years (Q1-Q3: 52-71 years), and 47% were Black patients. The median time from LVAD implantation to randomization was 115 days (Q1-Q3: 56-859 days). At 24 weeks, the primary composite outcome occurred in no patients receiving apixaban and in 2 patients (14%) receiving warfarin (P = 0.12); these 2 patients experienced major bleeding from gastrointestinal sources., Conclusions: Anticoagulation with apixaban was feasible in patients with an LVAD without an excess of HRAEs or deaths. This study informs future pivotal clinical trials evaluating the safety and efficacy of apixaban in LVAD recipients. (Evaluation of the Hemocompatibility of the Direct Oral Anti-Coagulant Apixaban in Left Ventricular Assist Devices [DOAC LVAD]; NCT04865978)., Competing Interests: Funding Support and Author Disclosures This study was sponsored by Inova Health System and funded by Abbott. Dr P. Shah has received grant support unrelated to this work and paid to Inova from Merck, Bayer, and Roche; and has served as a consultant for Natera, Merck, Ortho Clinical Diagnostics, and Procyrion. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Fenestrating a Fontan baffle has been associated with improved perioperative outcomes in patients with univentricular hearts. However, longer-term potential adverse effects remain debated. We sought to assess the impact of a fenestrated Fontan baffle on adverse cardiovascular events including all-cause mortality, cardiac transplantation, atrial arrhythmias, and thromboemboli., Methods: A multicentre North American retrospective cohort study was conducted on patients with total cavopulmonary connection Fontan baffle, with and without fenestration. All components of the composite outcome were independently adjudicated. Potential static and time-varying confounders were taken into consideration, along with competing risks., Results: A total of 407 patients were followed for 10.4 (7.1-14.4) years; 70.0% had fenestration of their Fontan baffle. The fenestration spontaneously closed or was deliberately sealed in 79.9% of patients a median of 2.0 years after Fontan completion. In multivariable analysis in which a persistent fenestration was modelled as a time-dependent variable, an open fenestration did not confer a higher risk of the composite outcome (hazard ratio, 1.18; 95% confidence interval, 0.71-1.97; P = 0.521). In secondary analyses, an open fenestration was not significantly associated with components of the primary outcome: that is, mortality or transplantation, atrial arrhythmias, or thromboemboli. However, sensitivity analyses to assess the possible range of error resulting from imprecise dates for spontaneous fenestration closures could not rule out significant associations between an open fenestration and atrial arrhythmias or thromboemboli., Conclusions: In this multicentre study, no significant association was identified between an open fenestration in the Fontan baffle and major adverse cardiovascular events., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Patients with left ventricular assist devices (LVADs) require interruption of warfarin for invasive procedures, but parenteral bridging is associated with many complications. Four-factor prothrombin complex concentrate (4F-PCC) can temporarily restore hemostasis in patients undergoing anticoagulation with warfarin., Objectives: This pilot study evaluated the strategy of using variable-dose 4F-PCC to immediately and temporarily reverse warfarin before invasive procedures without holding warfarin in patients with LVADs. The duration of effect of 4F-PCC on factor levels and time to reestablish therapeutic anticoagulation post procedure were assessed., Methods: Adult patients with LVADs and planned invasive procedures were enrolled from a single center. Warfarin was continued uninterrupted. The 4F-PCC dose administered immediately pre-procedure was based on study protocol. International normalized ratio (INR)- and vitamin K-dependent factor levels were collected before and during the 48 hours after 4F-PCC administration. The use of parenteral bridging, International Society for Thrombosis and Haemostasis major and clinically relevant nonmajor bleeding (CRNMB) and thromboembolic events at 7 and 30 days were collected., Results: In 21 episodes of 4F-PCC reversal, median baseline INR was 2.7 (IQR 2.2-3.2). The median dosage of 4F-PCC administered was 1794 units (IQR 1536-2130). At 24 and 48 hours post 4F-PCC administration, median INRs were 1.8 (IQR 1.7-2.0) and 2.0 (IQR 1.9-2.4). Two patients required postoperative bridging. One patient experienced major bleeding within 72 hours, and 2 experienced CRNMB within 30 days. There were no thromboembolic events. Baseline and post 4F-PCC vitamin K-dependent factor levels corresponded with changes in INR values. The median time to achieve therapeutic INR post-procedure was 2.5 days (IQR, 1-4)., Conclusion: Administration of 4F-PCC for temporary reversal of warfarin for invasive procedures in patients with LVADs allowed for continued warfarin dosing with minimal use of post-intervention bridging, limited bleeding and no thromboembolic events., Competing Interests: Disclosures JMC is a consultant for Abbott, Bristol Myers Squibb, and Pfizer and served on a scientific advisory board for Anthos, Bristol Myers Squibb, Roche, Sanofi, Werfen. MM reports payments made to Brigham and Women's Hospital from Abbott for consulting, consulting fees from Broadview Ventures, Natera, Paragonix, Moderna, and Baim Institute for Clinical Research; he is a scientific advisory board member for NuPulseCV, Leviticus, Transmedics, and FineHeart. MMG, ASW, SS, AEJ, KS, LC, BR have no conflicts to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Background: In patients with atrial fibrillation (AF) on vitamin K antagonist (VKA) therapy and therapeutic international normalized ratio (INR) range, the incidence of cardiac thromboembolism is not negligible, and the subgroup of patients who have a mechanical prosthetic mitral valve (PMV) has the highest risk. We aimed to assess the long-term effects of left atrial appendage closure (LAAC) in AF patients with a mechanical PMV who experienced a failure of VKA therapy., Methods: In this retrospective, multicentre study, patients underwent LAAC because of thrombotic events including transient ischemic attack and/or stroke, systemic embolism, and evidence of left atrial appendage thrombosis and/or sludge, despite VKA therapy, were enrolled. Patients with a mechanical PMV were included and compared with those affected by nonvalvular AF. The primary endpoint was the composite of all-cause death, major cardiovascular events, and major bleedings at follow-up. The feasibility and safety of LAAC also were assessed., Results: A total of 55 patients (42% female; mean age, 70 ± 9 years), including 12 with a mechanical PMV, were enrolled. The most-frequent indication to LAAC (71%) was LAA thrombosis or sludge. Procedural success was achieved in 96% of overall cases, and in 100% of patients with a PMV. In 35 patients, a cerebral protection device was used. During a median follow-up of 6.1 ± 4.3 years, 4 patients with a PMV, and 20 patients without a PMV, reported adverse events (hazard ratio 0.73 [95% confidence interval 0.25-2.16, P = 0.564])., Conclusions: LAAC seems to be a valuable alternative in patients with AF who have a mechanical PMV, with failure of VKA therapy. This off-label, real-world clinical practice indication deserves validation in further studies., (Copyright © 2024 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Introduction: A variety of thromboprophylaxis regimens have been administered in patients following the Fontan procedure. However, consensus guidelines regarding the optimal thromboprophylaxis strategy have not yet been developed., Method: A network meta-analysis was conducted to evaluate the comparative effectiveness among available thromboprophylaxis regimens and major bleeding events associated with these regimens., Results: A total of 28 comparative studies with 4430 Fontan patients were included. The incidence of thromboembolic events (TE) was significantly lower in individuals who underwent thromboprophylaxis compared to those who did not. Compared to a no-treatment strategy, nonvitamin K oral anticoagulants (NOACs) showed the largest treatment effect for preventing TE (OR = 0.08, 95 % CI 0.03 to 0.21), followed by warfarin (OR = 0.16, 95 % CI 0.10 to 0.27), and aspirin (OR = 0.23, 95 % CI 0.14 to 0.38). Indeed, NOACs were significantly more effective than aspirin in preventing TE (OR = 0.35, 95 % CI 0.14 to 0.84). Aspirin was associated with the lowest occurrence of major bleeding events, followed by NOACs, no medication, and warfarin. NOACs were shown to possess a highly favorable overall profile., Conclusion: Prescribing thromboprophylaxis drugs, either antiplatelets or anticoagulants, may be more effective in preventing TE after the Fontan operation than not doing so. Among the included regimens, NOACs demonstrated significantly greater efficacy than aspirin; however, they did not show statistically significant superiority over warfarin. Aspirin exhibited lower rates of major bleeding compared to both NOACs and warfarin. Overall, NOACs tended to offer the most advantageous balance of efficacy and safety. However, the findings should be interpreted considering the certainty and limitations of the evidence, including potential residual confounding in observational studies., Competing Interests: Declaration of competing interest All authors declare that there is no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Cardiac surgery poses a significant risk of perioperative bleeding and allogeneic blood transfusions, particularly in patients with bleeding disorders. Increasingly frequent use of coagulation factor concentrates could impact haemorrhagic risks, thromboembolic events, and costs. We describe the use of coagulation factor concentrates and allogeneic blood products in cardiac surgical patients with hereditary and acquired bleeding disorders to assess pertinent outcomes, including perioperative haemorrhage, thromboembolism, and hospital costs., Methods: We conducted a retrospective cohort study using the Premier Health Database, including adult cardiac surgical patients diagnosed with hereditary or acquired bleeding disorders compared with those without bleeding disorders., Results: Patients with acquired bleeding disorders required more extensive use of coagulation factor concentrates and blood products compared with those with hereditary bleeding disorders or without bleeding disorders. The highest exposures to coagulation factor concentrates were found in the acquired bleeding disorders group, with 24% receiving factor VIIa and 11.7% receiving prothrombin complex concentrate. This group also experienced significantly higher rates of complications, including a 15.8% rate of haemorrhage and a 19.2% rate of thromboembolic events. The acquired bleeding disorders group had longer intensive care and hospital stays, and the highest mortality rate (19.2%). The increased use of perioperative replacement of factor VIII and factor IX in the hereditary bleeding disorders group led to increased pharmacy costs but did not significantly impact blood bank charges., Conclusions: Acquired bleeding disorders in cardiac surgery patients are associated with increased use of haemostatic interventions, postoperative complications, and increased healthcare costs. Improved management of perioperative haemostasis and thromboprophylaxis strategies are essential for optimising patient outcomes and reducing expenses., (Copyright © 2024 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Introduction: The management of anticoagulation in patients with durable left ventricular assist devices (LVADs) is challenging. Traditionally, warfarin has been used, but its limitations have prompted interest in direct oral anticoagulants (DOACs). This meta-analysis aims to evaluate the safety and efficacy of DOACs compared to warfarin in LVAD patients., Methods: We searched databases for studies comparing DOACs and warfarin in LVAD patients. Primary outcomes were thromboembolic events and major bleeding events. Secondary outcomes were the individual components of the thromboembolic events, minor bleeding events, and all-cause mortality. Random-effects model was used to calculate log risk-ratios (RR) with 95 % confidence intervals (CI)., Results: Nine studies with a total of 316 LVAD patients (153 on DOACs, 163 on warfarin) were included. Thromboembolic events were similar between the groups (Log RR -0.42, 95 % CI:1.29 to 0.45, P = 0.34). Major bleeding events were significantly fewer in the DOAC group (Log RR -1.05, 95 % CI:1.73 to -0.36, P < 0.01). Minor bleeding events were also less common with DOACs (Log RR -0.77, 95 % CI:1.46 to -0.07, P = 0.03). No significant differences were observed in pump thrombosis, ischemic cerebrovascular accident events, or all-cause mortality., Conclusion: DOACs appear to be a safe and effective alternative to warfarin for anticoagulation in LVAD patients, associated with fewer major and minor bleeding events. These findings support the consideration of DOACs in this patient population, though further research is needed to confirm these results and guide clinical practice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Bleeding during cardiac surgery may be refractory to standard interventions. Off-label use of factor eight inhibitor bypass activity (FEIBA) has been described to treat such bleeding. However, reports of safety, particularly thromboembolic outcomes, show mixed results, and reported cohorts have been small., Methods: Adult patients undergoing cardiac surgery on cardiopulmonary bypass between July 1, 2018, and June 30, 2023, at Stanford Hospital (Stanford, California) were reviewed (n = 3,335). Patients who received FEIBA to treat postcardiopulmonary bypass bleeding were matched with those who did not by propensity scores in a 1:1 ratio using nearest neighbor matching (n = 352 per group). The primary outcome was a composite outcome of thromboembolic complications including any one of deep vein thrombosis, pulmonary embolism, unplanned coronary artery intervention, ischemic stroke, and acute limb ischemia, in the postoperative period. Secondary outcomes included renal failure, reoperation, postoperative transfusion, intensive care unit length of stay, and 30-day mortality., Results: A total of 704 encounters was included in this propensity-matched analysis. The mean dose of FEIBA administered was 7.3 ± 5.5 U/kg. In propensity-matched multivariate logistic regression models, there was no statistically significant difference in odds ratios for thromboembolic outcomes, intensive care unit length of stay, or mortality. Patients who received more than 750 U FEIBA had an increased odds ratio for acute renal failure (odds ratio, 4.14; 95% CI, 1.61 to 10.36; P < 0.001). In multivariate linear regression, patients receiving FEIBA were transfused more plasma and cryoprecipitate postoperatively. However, only the dose range of 501 to 750 U was associated with an increase in transfusion of erythrocytes (β, 2.73; 95% CI, 0.68 to 4.78; P = 0.009) and platelets (β, 1.74; 95% CI, 0.85 to 2.63; P < 0.001)., Conclusions: Low-dose FEIBA administration during cardiac surgery does not increase risk of thromboembolic events, intensive care unit length of stay, or mortality in a propensity-matched cohort. Higher doses were associated with increased acute renal failure and postoperative transfusion. Further studies are required to establish the efficacy of activated factor concentrates to treat refractory bleeding during cardiac surgery., (Copyright © 2024 American Society of Anesthesiologists. All Rights Reserved.)

Background: The benefit of oral anticoagulation in atrial fibrillation (AF) is well established for patients at elevated stroke risk, but less clear for those at intermediate risk. We investigated whether analysis of electrocardiogram (ECG) derived fibrillatory waves (F-waves) could help identify patients at risk for stroke and systemic embolism (SSE)., Methods: The Finnish Cardioversion (FinCV) study included patients not on permanent anticoagulation therapy who underwent cardioversion for an acute AF episode. We identified 739 individuals with a valid ECG and complete follow-up data. The maximum amplitudes of the F-waves in leads II and V1 were manually measured from the pre-procedure ECG. Patients were categorized into fine and coarse F-wave groups. The optimal lead and amplitude threshold for grouping were found in an events per person-years analysis. SSE were identified from the patient medical records until either anticoagulation was prescribed, AF was deemed chronic, the patient had deceased, or the end of follow-up., Results: Overall 37 (5.0%) patients suffered SSE during the median follow-up time of 5.4 years (1.9-10.8). Measured from lead V1 the SSE rates per 100 person-years were 1.5 and 0.7 in fine and coarse F-wave groups, respectively. Fine F-waves were observed in 112 (15.2%). Baseline characteristics were similar between the groups. Fine F-wave predicted SSE in a competing risk analysis (SHR 2.34, 95%CI 1.12-4.87, p  = .023). Analyses from lead II did not provide significant results., Conclusion: Electrocardiographic F-wave amplitude may provide additional information on stroke risk in patients with paroxysmal AF and borderline indications or contraindications for anticoagulation.

Currently, no consensus has been established on the most effective antithrombotic therapy to prevent thromboembolic and bleeding events in patients undergoing percutaneous left atrial appendage closure (LAAC) with preprocedural thromboembolic or bleeding events under oral anticoagulation (OAC) therapy. We retrospectively investigated the incidence of device-related thrombosis (DRT), thromboembolic events, and bleeding events in patients who underwent LAAC from September 2019 to October 2022. After categorizing patients into three groups based on preprocedural thromboembolic or bleeding events under OAC therapy, we compared the incidence of DRT and prognosis according to the postprocedural antithrombotic therapy. In patients who received the conventional antithrombotic therapy (OAC with and without single antiplatelet therapy for 45 days after LAAC and dual-antiplatelet therapy from 45 days to 6 months followed by single antiplatelet therapy), preprocedural thromboembolic events despite OAC were independently associated with DRT or postprocedural thromboembolic events at the 3 year follow-up (hazard ratio [HR] 4.55; 95% confidence interval [CI] 1.32-15.6; P = 0.016), whereas preprocedural bleeding events were independently associated with postprocedural bleeding events (HR 8.01, 95% CI 1.45-58.3; P = 0.036). Continuation of OAC for 12 months among patients who developed preprocedural thromboembolic events during OAC significantly decreased the incidence of DRT or postoperative thromboembolic events (P = 0.002) with no increase in the bleeding events (P = 0.522). Preprocedural thromboembolic and bleeding events can predict adverse events after LAAC with the conventional antiplatelet-based antithrombotic therapy. Patients who develop thromboembolic events under continuous OAC may benefit from continuous OAC for 1 year after LAAC., Competing Interests: Declarations Conflict of interest The authors declare that there are no conflicts of interest., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Background and Objectives: In patients with mechanical heart valves and recent intracranial hemorrhage (ICH), clinicians need to balance the risk of thromboembolism during the period off anticoagulation and the risk of hematoma expansion on anticoagulation. The optimal timing of anticoagulation resumption is unknown. We aimed to investigate the relationship between reversal therapy and ischemic stroke, between duration off anticoagulation and risk of ischemic strokes or systemic embolism and between timing of anticoagulation resumption and risk of rebleeding and ICH expansion., Methods: We conducted a retrospective cohort observational study in 3 tertiary hospitals. Consecutive adult patients with mechanical heart valves admitted for ICH between January 1, 2000, and July 13, 2022, were included. The primary end points of our study were thromboembolic events (cerebral, retinal, or systemic) while off anticoagulation and ICH expansion after anticoagulation resumption (defined by the following criteria: increase by one-third in intracerebral hematoma volume, increase by one-third in convexity subdural hemorrhage diameter, or visually unequivocal expansion of other ICH locations to the naked eye)., Results: A total of 171 patients with mechanical heart valves who experienced ICH were included in the final analysis. Most of the patients (79.5%) received reversal therapy for anticoagulation. Patients who received anticoagulation reversal therapy did not have increased risk of thromboembolic complications. Time off anticoagulation was not associated with risk of ischemic stroke; only 2 patients had a stroke within 7 days of the ICH, and both had additional major risk factors of thromboembolism. The rate of ischemic stroke/transient ischemic attack while off anticoagulation was lower than the rate of ICH expansion once anticoagulation was resumed (6.4% vs 9.9%). Furthermore, patients who developed ICH expansion had higher mortality compared with patients who had ischemic stroke while being off anticoagulation (41% vs 9%). Use of intravenous heparin bridging upon resumption of warfarin was strongly associated with increased risk of ICH expansion as compared with restarting warfarin without a heparin bridge., Discussion: Withholding anticoagulation for at least 7 days after ICH may be safe in patients with mechanical heart valves. Heparin bridging during anticoagulation resumption may be associated with increased risk of bleeding.

Background and Aims: Concerns about the safety of coronavirus disease 2019 (COVID-19) vaccines in patients with atrial fibrillation/flutter (AF/AFL) have arisen due to reports of thrombo-embolic events following COVID-19 vaccination in the general population. This study aimed to evaluate the risk of thrombo-embolic events after COVID-19 vaccination in patients with AF/AFL., Methods: This was a modified self-controlled case-series study using a comprehensive nationwide-linked database provided by the National Health Insurance Service in South Korea to calculate incidence rate ratios (IRRs) of thrombo-embolic events. The study population included individuals aged ≥12 years who were either vaccinated (e.g. one or two doses) or unvaccinated during the period from February to December 2021. The primary outcome was a composite of thrombo-embolic events, including ischaemic stroke, transient ischaemic attack, and systemic thromboembolism. The risk period was defined as 0-21 days following COVID-19 vaccination., Results: The final analysis included 124 127 individuals with AF/AFL. The IRR of thrombo-embolic events within 21 days after COVID-19 vaccination, compared with that during the unexposed control period, was 0.93 [95% confidence interval (CI) 0.77-1.12]. No significant risk variations were noted by sex, age, or vaccine type. However, patients without anticoagulant therapy had an IRR of 1.88 (95% CI 1.39-2.54) following vaccination., Conclusions: In patients with AF/AFL, COVID-19 vaccination was generally not associated with an increased risk of thrombo-embolic events. However, careful individual risk assessment is required when advising vaccination for those not on oral anticoagulant, as these patients exhibited an increased risk of thrombo-embolic events post-vaccination., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

&lt;b&gt;Introduction:&lt;/b&gt; Despite clear, relatively easy-to-use guidance, many clinicians find the perioperative management of direct oral anticoagulants (DOACs) challenging. Inappropriate antithrombotic management can delay procedures and lead to bleeding or thromboembolic complications.&lt;b&gt;Aim:&lt;/b&gt; We aimed to describe perioperative management practices related to planned procedures regarding DOACs in accordance with the applicable guidelines of cardiological and surgical societies.&lt;b&gt;Results:&lt;/b&gt; Perioperative management of DOAC therapy depends on many factors, and recommendations in the guidelines are not consistent.&lt;b&gt;Conclusions:&lt;/b&gt; The best approach to managing these patients is therefore to strike a balance between the risks of bleeding and thromboembolism.

This narrative review summarizes the current body of literature regarding periprocedural management of direct oral anticoagulant (DOAC)-treated patients undergoing digestive endoscopy since the publication of the 2022 American College of Gastroenterology - Canadian Association of Gastroenterology guidelines. We provide a detailed analysis of the thromboembolic risk, endoscopic procedure-specific bleeding risks, contemporary intraprocedural techniques to reduce the bleeding risk, and a summary of periprocedural DOAC guidelines developed by major gastrointestinal societies, including recommendations on procedure risk stratification. Despite data heterogeneity, the overall trend of the current literature supports the contemporary practice of a minimal DOAC interruption without the need for heparin bridging.