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Background: Hemophilia A (HA) is an X-linked bleeding disorder diagnosed by a deficiency in factor VIII (FVIII). For severe HA (SHA), prophylaxis clotting factor concentrates (CFC) has become the standard of care; however, it imparts a high treatment burden and typically results in an annualized bleeding rate (ABR) of 2-6. Emicizumab, a subcutaneously administered FVIII substitute, has become the de facto standard-of-care prophylaxis for children with SHA in many countries. Previous clinical trials of emicizumab have assessed ABR in patients greater than 12 years without inhibitors, and in children less than 12 years with inhibitors; however, there is little information published regarding the ABR of emicizumab compared to CFC in non-inhibitor SHA children., Methods: Using a retrospective electronic medical record chart review, we conducted a self-control analysis of 15 patients less than 12 years of age during equivalent periods of CFC versus emicizumab prophylaxis., Results: The mean ABR on CFC and emicizumab was 1.79 and 1.13 (p = .092), respectively, with a substantially decreased rate of joint bleeds (CFC 0.94; emicizumab 0.33; p = .001) and spontaneous bleeds (CFC 0.79; emicizumab 0.23; p = .008). No safety events were recorded for patients while administering emicizumab. The mean annual cost of CFC prophylaxis was $515,340 (SD $199,540), compared to $328,410 (SD $137,230) for emicizumab prophylaxis (p < .001)., Conclusion: Emicizumab resulted in an improved ABR compared to CFC, especially for joint and spontaneous bleeds, had fewer administration complications, and was substantially less expensive compared to CFC prophylaxis; however, more research is necessary for a complete understanding of the effect of emicizumab on joint health and muscle bleeds., (© 2024 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Purpose: This study was designed to investigate the impact of single-nucleotide polymorphism-encoded cytochrome P450 enzymes (CYP3A4/5) on clinical outcomes of rivaroxaban in patients with non-valvular atrial fibrillation (NVAF) based on pharmacokinetics and pharmacodynamics (PK/PD) aspects., Method: A prospective study enrolling 165 rivaroxaban-treated patients with NVAF was conducted. Genotyping of CYP3A4 (rs2242480, rs2246709, rs3735451, and rs4646440) and CYP3A5 (rs776746) was performed to explore their impact on the trough plasma concentrations (C trough ) of rivaroxaban, coagulation indicators at the C trough including activated partial thromboplastin time (APTT) and prothrombin time (PT), and clinical outcomes., Results: Patients with mutant genotype CYP3A4 (rs2242480, rs2246709, and rs3735451) and CYP3A5 (rs776746) had higher levels of rivaroxaban C trough , PT values than that of wild-type. Furthermore, a positive relationship was revealed between C trough and PT (r = 0.212, p = 0.007), while no significant correlation was found between C trough and APTT. Regarding the clinical outcomes, the minor allele carriers on rs3735451 and the minor allele (A) carriers on rs2246709 were associated with higher incidence of minor bleeding (p = 0.028 and p = 0.038, respectively) and were identified as the independent risk factors of minor bleeding treated with rivaroxaban (p = 0.024 and p = 0.036, respectively), with the receiver operating characteristic (ROC) curve validated (AUC = 0.8956, 95% CI: 0.829-0.962)., Conclusion: The CYP3A4 polymorphisms (rs2242480, rs2246709, and rs3735451) and CYP3A5 rs776746 were associated with variations in rivaroxaban PK/PD. The minor allele (C) carriers on rs3735451 and the minor allele (A) carriers on rs2246709 were correlated with clinical outcomes., Competing Interests: Declarations. Ethics Approval: This study was performed in line with the principles of the Declaration of Helsinki. The Ethics Committee of Zhongshan Hospital, Fudan University, approved this study. Consent to Participate: Informed consent was obtained from all individual participants included in the study. Consent for Publication: All authors have given their consent for publication. Competing Interests: The authors declare no competing interests., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Source Citation: Bajraktari G, Bytyçi I, Abdyli G, et al. One-month dual antiplatelet therapy reduces major bleeding compared with longer-term treatment without excess stent thrombosis: a systematic review and meta-analysis of randomized clinical trials. Am J Cardiol. 2024;227:91-97. 39029722., Competing Interests: Disclosures: Disclosure form is available with the article online.

Objective: To assess the characteristics and clinical outcomes of patients with lower extremity peripheral artery disease (PAD) in XATOA receiving dual pathway inhibition (DPI) with rivaroxaban 2.5 mg twice daily plus aspirin according to lower extremity revascularisation (LER) history., Methods: XATOA is an international, multicentre, prospective, single arm registry study. This subanalysis investigated patients with lower extremity PAD according to LER history. Patients with coronary artery disease, PAD, or both, receiving DPI were followed for 12 or more months. Baseline characteristics and clinical outcomes were assessed according to LER history. A time dependency analysis assessed outcomes by time between the most recent LER procedure and the start of DPI. A multivariable analysis assessed the influence of patient characteristics on clinical outcomes., Results: In XATOA (n = 5 532), 2 820 (51.0%) patients had lower extremity PAD, of whom 1 736 (61.6%) had prior LER and 1 084 (38.4%) had no prior LER. Baseline characteristics were generally similar between patients with or without prior LER. A higher proportion of patients with prior LER experienced any treatment emergency clinical events compared with those without prior LER (15.0% vs. 9.4%, respectively), with greater differences observed between incidence rates of limb events, including major adverse limb events (9.06 vs. 4.09 events per 100 patient years, respectively). Similar rates of myocardial infarction, stroke, and major bleeding were observed in both subgroups. Clinical event rates were generally higher in patients who had previous LER for six months or less compared with patients who had previous LET for more than six months before starting DPI, regardless of LER type. Multivariable analyses showed that prior LER was predictive of limb events., Conclusion: This subanalysis of XATOA found that prior LER was associated with increased rates of limb events, consistent with results of COMPASS and VOYAGER PAD. Rates of bleeding were also low regardless of LER history and consistent with the findings from these trials., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: To evaluate whether warfarin targeted at an international normalized ratio of 1.8 (range, 1.5-2.0) after On-X mechanical aortic valve implant is safe for all patients., Methods: This prospective, observational clinical registry assessed adverse event rates in adult patients receiving low-dose warfarin (target international normalized ratio, 1.8; range, 1.5-2.0) plus daily aspirin (75-100 mg) during a 5-year period after On-X aortic valve implant. The primary end point is the combined rate of major bleeding, valve thrombosis, and thromboembolism overall and in 4 subgroups. The comparator is the Prospective Randomized On-X Anticoagulation Trial control group patients on standard-dose warfarin (international normalized ratio, 2.0-3.0) plus aspirin 81 milligrams daily., Results: A total of 510 patients were recruited at 23 centers in the United States, United Kingdom, and Canada between November 2015 and January 2022. This interim analysis includes 229 patients scheduled to complete 5-year follow-up by August 16, 2023. The linearized occurrence rate (in percent per patient-year) of the primary composite end point of major bleeding, valve thrombosis, and thromboembolism is 1.83% compared with 5.39% (95% confidence interval, 4.12%-6.93%) in the comparator group. Results are consistent in clinic-monitored and home-monitored patients and in those at high risk for thromboembolism. Major bleeding and total bleeding were reduced by 87% and 71%, respectively, versus the comparator group, without an increase in thromboembolic events., Conclusions: Interim results support the continued safety of the On-X aortic mechanical valve with a target international normalized ratio of 1.8 plus low-dose aspirin through 5 years after implant, with or without home monitoring., Competing Interests: Conflict of Interest Statement M.W.G., M.J.P., M.J., A.Y.O., M.L., G.M.T., J.Z., and M.S. hold a consulting agreement with Artivion. R.C.H. reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: The purpose of this study was to evaluate the association between different antiplatelet therapy regimens and the functional outcomes and bleeding complications among mild-to-moderate ischaemic stroke patients based on real-world data., Methods: We used data from the SEACOAST trial (Safety and efficacy of aspirin-clopidogrel in acute noncardiogenic minor ischaemic stroke) to analyse the data of patients with mild-to-moderate stroke within 72 h after onset who were treated with aspirin or clopidogrel alone or a combination of clopidogrel and aspirin from September 2019 to November 2021. Propensity score matching (PSM) was used to balance the differences between groups. We performed an analysis to evaluate the association of different antiplatelet regimens and 90-day disability, which was defined as a modified Rankin Scale score ≥2, as well as disability ascribed to index or recurrent stroke by the local investigator. In terms of safety, we then compared the bleeding events between the two groups., Results: A total of 2822 mild-to-moderate ischaemic stroke patients were treated with either clopidogrel plus aspirin (n = 1726, 61.2%) or aspirin/clopidogrel (n = 1096, 38.8%). Of 1726 patients in the dual antiplatelet group, 1350 (78.5%) received less than or equal to 30 days of combined therapy. At 90 days, 433 (15.3%) patients were disabled. Patients who received combined therapy had a lower overall disability rate (13.7% versus 17.9%; OR 0.78 (0.6-1.01); P = 0.064). However, investigators found that index stroke was the reason for significantly fewer patients in the dual antiplatelet group having disability (8.4% versus 12%; OR, 0.72 (0.52-0.98); P = 0.038). There was no statistically significant difference in the incidence of moderate to severe bleeding complications between the dual and mono antiplatelet drug regimens (0.4% versus 0.2%; HR 1.5 (0.25, 8.98); P = 0.657)., Conclusion: Aspirin plus clopidogrel was associated with a reduction in the incidence of disability attributed to index stroke. There was no statistically significant difference in the incidence of moderate to severe bleeding complications between the two antiplatelet drug regimens., Trial Registration Number: ChiCTR1900025214., Competing Interests: Declarations. Ethics Approval: This study was approved by the Ethics Review Board of the First Hospital of Shanxi Medical University. Informed Consent: All the participants provided written informed consent. Consent for Publication: We all agree to have our manuscript published in Cardiovascular drugs and therapy. Competing Interests: The authors state that there is no conflict of interest., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Inconclusive and limited results have been reported on the clinical utility of CYP2C19 genotyping in stroke/TIA patients of non-East Asian ancestries. We herein performed an updated systematic review and meta-analysis to quantitatively estimate the association of CYP2C19 loss-of function (LOF) status with efficacy and safety of clopidogrel-based antiplatelet therapy in non-East Asian patients affected by stroke or TIA., Methods: A comprehensive search was performed up to July 2023 using PubMed, Web of Knowledge, and Cochrane Library databases. The clinical outcomes investigated were stroke, composite vascular events and bleeding. Pooled estimates were calculated as risk ratios (RR) with 95% CI using the Mantel- Haenszel random-effects model. The quality of evidence was assessed using the GRADEpro tool., Results: A total number of 1673 stroke/TIA patients from 8 non-East Asian studies, published between 2014 and 2022, were included in the systematic review. Clopidogrel-treated carriers of CYP2C19 LOF alleles were found at increased risk of stroke compared to non-carriers (RR: 1.68, 95%CI: 1.04-2.71, P = 0.03). However, no significant association was observed with the risk of composite vascular events (RR: 1.15, 95%CI: 0.58-2.28, P = 0.69) or bleeding (RR: 0.84, 95%CI: 0.38-1.86, P = 0.67). Similarly, European ancestry patients carrying CYP2C19 LOF alleles displayed a higher risk of stroke (RR: 2.69 (1.11-6.51, P = 0.03), but not of composite vascular events or bleeding., Conclusion: The present updated meta-analysis provides moderate quality evidence of association between CYP2C19 LOF alleles and an increased risk of stroke in non-East Asian patients with stroke/TIA after receiving clopidogrel therapy. Further large pharmacogenetic studies are still warranted to corroborate these findings., Competing Interests: Declarations. Competing interests: The authors have no relevant financial or non-financial interests to disclose. Ethics Approval: This article does not contain any studies with human participants or animals performed by any of the authors. Consent to Participate: Not applicable. Consent for Publication: Not applicable., (© 2023. The Author(s).)

Background: This review aims to evaluate the safety and efficacy of apixaban vs. vitamin K antagonists (VKAs) in patients on dialysis., Methods: All types of studies published on PubMed, Embase, CENTRAL, and Web of Science up to 10 September 2023 and comparing outcomes of apixaban vs. VKA in dialysis patients were eligible., Results: Two randomized controlled trials (RCTs) and six retrospective studies were included. Apixaban treatment was associated with significantly lower risk of major bleeding (RR: 0.61; 95% CI: 0.48, 0.77; I 2  = 50%) and clinically relevant non-major bleeding (RR: 0.82, 95% CI: 0.68, 0.98, I 2  = 9%) compared to VKA. Meta-analysis also showed that the risk of gastrointestinal bleeding (RR: 0.74, 95% CI: 0.64, 0.85, I 2  = 16%) and intracranial bleeding (RR: 0.64, 95% CI: 0.49, 0.84, I 2  = 0%) was significantly reduced with apixaban. Meta-analysis showed no difference in the risk of ischemic stroke (RR: 0.40, 95% CI: 0.06, 2.69, I 2  = 0%), mortality (RR: 1.26, 95% CI: 0.74, 2.16, I 2  = 94%) and recurrent venous thromboembolism (RR: 1.02, 95% CI: 0.87, 1.21, I 2  = 0%) between the two groups. Subgroup analysis of RCTs showed no difference in bleeding outcomes., Conclusions: Low-quality evidence from a mix of RCTs and retrospective studies shows that apixaban may have better safety and equivalent efficacy as compared to VKA in dialysis patients. Apixaban treatment correlated with significantly reduced risk of major bleeding and clinically relevant nonmajor bleeding in observational studies but not in RCTs. The predominance of retrospective data warrants caution in the interpretation of results.

Background: There are no clinical trials with a head-to-head comparison between the 2 most commonly used oral anticoagulants (apixaban and rivaroxaban) in patients with atrial fibrillation (AF). The comparative efficacy and safety between these drugs remain unclear, especially in older patients who are at the highest risk for stroke and bleeding., Objective: The purpose of this study was to compare the risk of major bleeding and thromboembolic events between apixaban and rivaroxaban in older patients with AF., Methods: We conducted a population-based retrospective cohort study of all adult patients (66 years or older) with AF in Ontario, Canada, who were treated with apixaban or rivaroxaban between April 1, 2011, and March 31, 2020. The primary safety outcome was major bleeding, and the primary efficacy outcome was thromboembolic events. Secondary outcomes included any bleeding. Rates and hazard ratios (HRs) were adjusted for baseline comorbidities with inverse probability of treatment weighting., Results: This study included 42,617 patients with AF treated with apixaban and 30,725 patients treated with rivaroxaban. After inverse probability of treatment weighting using the propensity score, patients in the apixaban and rivaroxaban groups were well balanced for baseline values of demographic characteristics, comorbidities, and medications; both groups had a similar mean age of 77.4 years, and 49.9% were female. At 1 year, the apixaban group had a lower risk for both major bleeding with an absolute risk reduction at 1 year of 1.1% (2.1% vs 3.2%; HR 0.65; 95% confidence interval [CI] 0.59-0.71]) and any bleeding (8.1% vs 10.9%; HR 0.73; 95% CI 0.69-0.77), with no difference in the risk for thromboembolic events (2.2% vs 2.2%; HR 1.02; 95% CI 0.92-1.13)., Conclusion: In patients with AF, 66 years or older, treatment with apixaban was associated with lower risk for major bleeding, with no difference in the risk for thromboembolic events compared with rivaroxaban., Competing Interests: Disclosures Dr Shurrab is supported by a Research Chair in Cardiovascular Health, Health Sciences North Research Institute, Sudbury, Ontario. Dr Tu is supported by the Chair in Family and Community Medicine Research in Primary Care at UHN Department of Family and Community Medicine and receives a Research Scholar Award from the Department of Family and Community Medicine at the University of Toronto. Dr Turakhia has received research grants from Bristol Myers Squibb, American Heart Association, Bayer, Gilead Sciences, and the Food and Drug Administration and consulting fees from Medtronic, Pfizer, Johnson & Johnson, and AliveCor. He owns equity in iRhythm, Connect America, Forward, Evidently, and PocketRN. Dr Turakhia is an employee of iRhythm Technologies Inc., which manufactures ambulatory electrocardiogram monitors, but this work was not supported by the company and was performed exclusively in his academic role. Dr Lopes has received research grants or contracts from Amgen, Bristol Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi-Aventis as well as funding for educational activities or lectures from Pfizer, Bristol Myers Squibb, Novo Nordisk, and AstraZeneca and funding for consulting from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Novo Nordisk, and AstraZeneca. Dr Castellucci’s research institution has received honoraria from Bayer, Bristol Myers Squibb–Pfizer Alliance, the ACADEMY for Continued Advancement in Healthcare Education, Amag Pharmaceutical, LEO Pharma, Sanofi, Valeo Pharma, and Servier. Dr Ko is supported by the Jack Tu Chair in Cardiovascular Outcomes Research, Sunnybrook Hospital, and the University of Toronto. The remaining authors have nothing to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Approximately 7% of patients with newly diagnosed multiple myeloma (MM) experience bleeding complications with varying causes, but few reports have described these complications. Here we report the case of a patient with newly diagnosed MM who presented with a bleeding tendency and various coagulation abnormalities. Chromogenic assays, thrombin time, and reptilase time revealed the presence of a thrombin-inhibiting substance that inhibited release of fibrinopeptide A from fibrinogen. The coagulation abnormalities improved after treatment with daratumumab, lenalidomide, and dexamethasone. As the thrombin inhibition mechanism remains unclear, no previous studies have reported recent treatment outcomes in older patients producing thrombin-inhibiting substances, which can hinder clinical treatment. Therefore, we believe that the diagnosis and the treatment course of this case provide valuable information. Moreover, such case reports provide significant insights into the pathophysiology of bleeding complications associated with MM., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2024. Japanese Society of Hematology.)

Introduction and Objectives: The optimal chronic antithrombotic regimen for patients with atrial fibrillation undergoing transcatheter aortic valve implantation (TAVI) remains uncertain. Our aim was to compare the incidence of late bleeding events between patients on direct oral anticoagulants (DOACs) and those on vitamin-K antagonists (VKA)., Methods: This single-center observational study included TAVI patients requiring oral anticoagulation at discharge between 2015 and 2021. The primary endpoint was any clinically significant bleeding event. Secondary endpoints were stroke, heart failure, and all-cause mortality., Results: A total of 702 TAVI procedures were performed, with 297 patients requiring oral anticoagulation at discharge. Among them, 206 (69.4%) received VKA and 91 (30.6%) received DOAC. Baseline clinical, procedural and in-hospital characteristics did not significantly differ between groups, except for better renal function among DOAC patients. The median length of follow-up was 2.8 years. The risk of bleeding events was higher in patients receiving DOACs than in those receiving VKA (HR, 2.27; 95%CI, 1.21-4.26; incidence of 9.7 and 4.2 events per 100 patient-years of follow-up for DOAC and VKA patients, respectively). There were no statistically significant differences in the rates of stroke (HR, 1.28; 95%CI, 0.4-4.3), heart failure hospitalization (HR, 0.92; 95%CI, 0.46-1.86), or all-cause mortality (HR, 1.02; 95%CI, 0.68-1.55)., Conclusions: In older patients undergoing TAVI and receiving anticoagulant therapy for atrial fibrillation, the use of DOAC was associated with a higher risk of late bleeding events than VKA., (Copyright © 2024 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Should we rely on anticoagulation monitoring in ECMO patients or simply flip a coin? The increasing use of anti-factor Xa activity to monitor the effect of UFH appears appropriate, given its moderate correlation with the UFH infusion rates, and it may play a role in preventing thromboembolic events. However, to avoid bleeding complications, more sophisticated tools, and careful clinical decision-making remain essential., (© 2024 The Author(s). Clinical Cardiology published by Wiley Periodicals, LLC.)

Atrial fibrillation (AF) is the most common cardiac dysrhythmia and a common cause of ischemic stroke. Stroke prevention with oral anticoagulation (OAC) is the cornerstone of AF management. Patients and their treating physicians may have different views on different attributes of OACs. The objective of this study was to quantify the relative importance that patients and physicians in Turkey place on different OAC attributes when making treatment decisions in AF. A cross-sectional survey was administered to AF patients (≥ 50 years) receiving OAC and practising cardiologists, including residents with ≥ 2 years of experience in Turkey. For both patients (N = 230; 50% male) and physicians (N = 194; 74% male), the most important attributes for OAC treatment decision making in AF were "success in preventing stroke" (57% and 73.9% or overall importance, respectively) and "risk of major bleeding" (20% and 23.4%, respectively). For patients, other attributes were much less important, but not altogether unimportant: reversal agent availability (7%), monitoring (5%), food or drug interactions (3%), minor bleeding (3%), and ease of swallowing (2%). For physicians, among the other attributes, only the need for monitoring (1.3%) had a relative importance of > 1%. For all Turkish participants, efficacy and safety were found to be the most important attributes influencing OAC choice in AF with these two attributes accounting for 77% and 97.3% of overall importance for patients and physicians, respectively. Certain considerations, especially reversal agent availability and monitoring appear to be more important to patients than to physicians This is the first study to use BWS to quantify patient and physician preferences for OAC treatments in AF in Turkey., (© 2024 The Author(s). Clinical Cardiology published by Wiley Periodicals, LLC.)

Background: Current guidelines recommend at least 12 months of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). However, DAPT prolonged use may increase the risk of bleeding complications. Therefore, we aimed to perform a meta-analysis to assess whether ticagrelor monotherapy after ≤1 month of DAPT improves clinical outcomes compared with continued DATP in acute coronary syndrome (ACS) patients post-PCI., Methods: We systematically searched PubMed, Embase and Cochrane databases for randomized controlled trials published up to August 2024. All-cause and cardiovascular death, overall and major bleeding events, myocardial infarction (MI), stroke, target vessel revascularization (TVR) and stent thrombosis within 1-2 years post-procedure were evaluated. Statistical analysis was performed using Review Manager 5.1.7., Results: Three studies and 13,737 patients were included, of whom 6861 (49.95 %) received ticagrelor alone. When compared with DAPT, ticagrelor monotherapy significantly reduced the risk of overall (2.0 % vs 4.5 %; RR 0.44; 95 % Cl 0.33-0,59; p < 0.00001) and major (1.4 % vs 2.5 %; RR 0.49; 95 % Cl 0.29-0.83; p = 0.04) bleeding events. Both antiplatelet regimens had similar rates of mortality, MI, stroke, TVR or stent thrombosis., Conclusion: This meta-analysis suggests that ticagrelor alone after ≤1 month of DAPT post-PCI in ACS patients reduces bleeding complications without increasing major adverse events compared with traditional DAPT for 12 months., Competing Interests: Declaration of competing interest None of the authors has any conflict of interest to disclose., (Copyright © 2024 Elsevier Inc. 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: The ONCO DVT study (Edoxaban for 12 Months Versus 3 Months in Patients With Cancer With Isolated Distal Deep Vein Thrombosis) revealed superiority of 12-month relative to 3-month edoxaban treatment for the thrombotic risk in cancer-associated isolated distal deep vein thrombosis. However, it is unknown whether the superiority could be common in different modified Ottawa score subgroups., Objectives: To identify more preferable candidates for extended anticoagulation in patients with cancer-associated isolated distal deep vein thrombosis using the modified Ottawa score., Methods: In this post-hoc subgroup analysis of the ONCO DVT study, we stratified 601 patients into the low (≤-1, N = 126), intermediate (0, N = 323), and high (≥1, N = 152) modified Ottawa score subgroups and compared clinical outcomes between the 12-month and 3-month edoxaban treatment groups., Results: The cumulative incidence of symptomatic recurrent venous thromboembolism or venous thromboembolism-related death was not different between the 12-month and 3-month edoxaban treatment groups in the low score subgroup (0.0% vs 2.2%), whereas it was lower in the 12-month than in the 3-month edoxaban treatment group in the intermediate (0.8% vs 7.6%) and high (3.1% vs 15.6%) score subgroups. There were no significant differences in the cumulative incidences of the major bleeding between the 12-month and 3-month edoxaban treatment groups in the low (10.1% vs 7.6%), intermediate (8.8% vs 5.0%), and high (13.9% vs 12.6%) score subgroups., Conclusion: A 12-month compared with 3-month edoxaban treatment showed a lower risk of thrombotic events in patients with cancer-associated isolated distal deep vein thrombosis in the intermediate and high modified Ottawa score subgroups but not in the low score subgroup, suggesting a limited benefit of extended anticoagulation therapy beyond 3 months in patients with low modified Ottawa score., Competing Interests: Declaration of competing interests Y.Y. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi Sankyo and grant support from Bayer Healthcare and Daiichi Sankyo. T.M. reports lecturer's fees from AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Japan Lifeline, Kowa, Pfizer, and Tsumura; manuscript fees from Bristol-Myers Squibb and Pfizer; and advisory board for Novartis and Teijin. Y.N. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi Sankyo. Y.O. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi Sankyo and research funds from Bayer Healthcare and Daiichi Sankyo. N.I. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, and Daiichi Sankyo. Y.T. received lecture fees from AstraZeneca, Chugai Pharmaceutical, Bristol-Myers Squibb, Kyowa Kirin, Pfizer, Taiho Pharmaceutical, Takeda Pharmaceutical, and Daiichi Sankyo and grant support from Daiichi Sankyo, AstraZeneca, and Ono Pharmaceutical. S.I. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, and Daiichi Sankyo. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Abstract: Extracorporeal membrane oxygenation (ECMO) is a mechanical support treatment modality used in patients with refractory cardiac and/or pulmonary failure. Bleeding and thrombotic complications associated with ECMO are inherent concerns that require careful management. Anticoagulation optimization may help mitigate these risks by providing more adequate therapeutic anticoagulation and lessen the bleed risk. Heparin, the most used anticoagulant, carries concerns for heparin-induced thrombocytopenia and possible resistance given its dependence on cofactors and circulating proteins to exert its pharmacologic effect. In contrast, bivalirudin, a direct thrombin inhibitor, exerts its effect independent of cofactors or plasma proteins, and possesses thrombin-binding and metabolism features that may confer advantages in ECMO management. This review of the evidence for bivalirudin utilization in ECMO suggests favorable outcomes in circuit-related thrombosis, bleeding, and dosing reliability. In addition, blood product utilization, circuit interventions, and success in ECMO decannulation and survival were positive findings associated with bivalirudin that merit consideration. Common questions and concerns relative to bivalirudin utilization, including laboratory monitoring, utilization in low-flow states, dosing considerations in renal replacement therapy, reversibility, and cost are also discussed in this review. Moreover, this review suggests that bivalirudin utilization presents the opportunity for ECMO management simplification., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

When selecting an anticoagulant, clinicians consider individual patient characteristic, the treatment indication, drug pharmacology, and safety and efficacy as demonstrated in randomized trials. An ideal anticoagulant prevents thrombosis with little or no increase in bleeding. Direct oral anticoagulants represent a major advance over traditional anticoagulants (e.g., unfractionated heparin, warfarin) but still cause bleeding, particularly from the gastrointestinal tract which can limit their use. Epidemiological studies indicate that patients with congenital factor XI (FXI) deficiency have a lower risk of venous thromboembolism (VTE) and ischemic stroke (IS) than non-deficient individuals, and do not have an increased risk of spontaneous bleeding, even with severe deficiency. These observations provide the rationale for targeting FXI as a new class of anticoagulant. Multiple FXI inhibitors have been introduced and several are being evaluated in Phase III trials. In this review, we explain why drugs that target FXI may be associated with a lower risk of bleeding than currently available anticoagulants and summarize the completed and ongoing trials., Competing Interests: Declarations. Conflict of interest: Renato D. Lopes- Research grants or contracts from Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, Sanofi-Aventis; funding for educational activities or lectures from Pfizer, Daiichi Sankyo, and Novo Nordisk; and funding for consulting or other services from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Novo Nordisk. C. Michael Gibson- research grants support from Johnson & Johnson and Bristol-Myers Squibb. John W. Eikelboom- received honoraria and/or research support from: AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi, Merck, Janssen, Pfizer, Servier, and Ionis., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Antithrombotic treatment in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) poses a dilemma. We compared outcomes of dual antithrombotic therapy (DAT) (direct oral anticoagulants (DOACs)/warfarin + antiplatelets) vs triple antithrombotic therapy (TAT) (DOACs/warfarin, aspirin, and P2Y12 inhibitor) in this population. Multiple databases were searched from inception to December 17, 2023 to identify randomized controlled trials (RCTs) comparing DAT vs TAT in patients with AF and ACS. Outcomes included major adverse cardiac events (MACE), bleeding events, stroke, stent thrombosis, and myocardial infarction (MI). Relative risk and 95% confidence intervals were estimated with a random-effects model using the inverse-variance technique. We assigned I 2  > 50% as an indicator of statistical heterogeneity. p -Value <0.05 was considered significant. Ten RCTs comprising 6186 patients on TAT (female 26%, mean age 71 ± 9 years) and 6800 patients on DAT (female 27%, mean age 71 ± 9 years) were included. Patients receiving DAT experienced lower rates of bleeding events compared to those receiving TAT, with relative risks of 0.69 [0.55-0.87] ( p  < 0.001), 0.65 [0.40-1.06] ( p  = 0.09), and 0.62 [0.46-0.84] ( p  < 0.001) for TAT durations of 3, 6, and 12 months, respectively. No difference was seen in the occurrence of MACE, MI, stroke, or stent thrombosis between DAT and TAT across all three durations of TAT. This is the largest pooled analysis comparing TAT to DAT stratified by the duration of antithrombotic therapy. Our results revealed that DAT was associated with reduced bleeding risk despite no difference in other outcomes., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: As per current guidelines, acute coronary syndrome (ACS) patients who undergo percutaneous coronary intervention (PCI) should be started on dual antiplatelet therapy (DAPT) for a period of 12 months., Objective: To assess the efficacy and safety of brief DAPT (up to 3 months) succeeded by ticagrelor monotherapy compared with a 12-month DAPT in ACS patients following PCI., Methods: We systematically searched Cochrane, Embase, and PubMed to find relevant randomized clinical trials. Examined outcomes included the incidence of major adverse cerebrovascular and cardiovascular events (MACCE), bleeding events, and the composite incidence of net adverse clinical events (NACE)., Results: Our primary analysis included 21,927 ACS patients from six RCTs. Our pooled results indicate that following PCI in individuals with ACS, brief DAPT followed by ticagrelor did not increase the risk of MACCE (OR 0.92, 95% CI 0.79-1.07) but significantly reduced the risk of minor or major bleeding (OR 0.52, 95% CI 0.44-0.62) and NACE (OR 0.71, 95% CI 0.59-0.86) compared with a long-term DAPT within a follow-up of 12 months., Conclusion: Brief DAPT followed by ticagrelor monotherapy is superior to a 12-month DAPT in offering a net clinical advantage in ACS patients following PCI., Competing Interests: Declarations Ethics approval The present meta-analysis does not involve direct data collection from human subjects or animals. All data used in this study were obtained from previously published and publicly available sources, adhering to the ethical guidelines of the respective studies. No identifiable patient information is presented in this meta-analysis. Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The optimal low-dose antiplatelet agents in patients with coronary heart disease (CHD) had not been determined. The objective of this study was to compare the impact of different low-dose antiplatelet agents on cardiovascular outcomes and bleeding risks in patients with CHD., Methods: We searched PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, VIP, WanFang Data, and China Biology Medicine. Randomized controlled trials (RCTs) enrolling patients with CHD treated with different low-dose platelet aggregation inhibitors were included. The revised Cochrane Risk of Bias Tool for Randomized Trials Risk was used to assess risk of bias in RCTs. A Bayesian random network meta-analysis (NMA) was conducted, with odds ratios (OR) and 95% confidence intervals (CI) as effect estimates in R 4.2.2 software and Stata 15.0. The quality of evidence was assessed using the Confidence in NMA framework., Results: Sixteen RCTs involving 6350 patients were included. All participants were treated with a recommended dose of aspirin plus a low or standard dose of P2Y12 receptor antagonist. Low-level evidence indicated the risk of major adverse cardiovascular events (MACE) was similar among low doses of prasugrel, ticagrelor, standard doses of prasugrel, ticagrelor, and clopidogrel. Low- to moderate-level evidence suggested there was no difference in bleeding risk among low dose of prasugrel, ticagrelor, clopidogrel compared to standard dose of prasugrel, ticagrelor, and clopidogrel. NMA showed that low dose of prasugrel had the highest probability of being the best intervention in terms of MACE, myocardial infarction, and bleeding events leading to discontinuation., Conclusion: Based on low-level evidence, low dose of prasugrel combined with standard dose of aspirin can be recommended for patients with CHD, low dose of ticagrelor was similar in terms of MACE and bleeding compared with standard dose of P2Y12 receptor antagonist. The systematic review was registered in PROSPERO with the registration number CRD42023438376., (© 2024 The Author(s). Journal of Evidence‐Based Medicine published by Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.)

Background: Coronary artery disease (CAD) and atrial fibrillation (AF) often coexist, but the impact of clinical phenotypes of CAD on outcomes in AF patients in the non-vitamin K antagonist oral anticoagulant drugs (NOACs) era is less well understood., Methods: This was a post-hoc of the GLORIA-AF registry, a global, multicenter, prospective AF registry study. Patients were divided into three groups: prior history of myocardial infarction (MI)/unstable angina group (Group 1); stable angina group (Group 2); and a control group without stable angina or history of MI/unstable angina. The primary endpoint was the composite of all-cause death or stroke, and the safety endpoint was major bleeding., Results: A total of 24,827 patients were included in this analysis (median age was 71 (IQR, 64-78) years; 55% male) and 5394 (21.7%) had CAD. During a follow-up of 2 years, the incidence of the primary endpoint was 5.99 (95% CI, 5.33, 6.71) per 100 patient-years in Group 1, 4.04 (95% CI, 3.55, 4.70) per 100 patient-years in Group 2, and 2.79 (95% CI, 2.62, 2.96) per 100 patient-years in the control group (p < .001). Compared the control group, the adjusted hazard ratio of the primary composite endpoint in Groups 1 and 2 were 1.58 (95% CI, 1.37, 1.83, p < .001) and 1.22 (95% CI, 1.04, 1.43, p = .012), respectively. Among anticoagulated patients with AF and CAD, NOACs were associated with a reduced risk of the primary composite endpoint and major bleeding, compared with vitamin K antagonists (VKA)., Conclusions: CAD was prevalent in patients with AF, and clinical phenotypes of CAD influenced outcomes in patients with AF, with a history of MI/unstable angina being associated with a significantly increased risk of CV events, compared to stable angina. NOACs were superior to VKA in terms of the effectiveness and safety outcomes in patients with AF and concomitant CAD., (© 2025 The Author(s). European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Introduction: Guidelines for managing left ventricular thrombus remain limited, particularly when incorporating oral anticoagulants into dual antiplatelet therapy for acute myocardial infarction. This study aims to assess the safety and efficacy of direct oral anticoagulants (DOACs) vs vitamin K antagonists (VKAs) in managing left ventricular thrombus among patients with and without recent myocardial infarction., Methods: This retrospective observational study used data from the TriNetX research network. Patients with left ventricular thrombus treated with either DOACs or VKAs between December 1, 2013 and December 1, 2023, were included. Subgroup analyses were conducted for patients with or without recent acute coronary syndrome (<1 month). Risk and Kaplan-Meier survival analysis were conducted at 90 days after the indexed event., Results: A total of 39,770 patients were included. DOACs treatment had lower rates of stroke (11.8% vs 13.7%; relative risk [RR] 0.859; 95% confidence interval [CI], 0.816-0.905; P < .001), major bleeding (4.8% vs 5.3%; RR 0.902; 95% CI, 0.829-0.982; P = .018), and systemic embolism (3.5% vs 4.2%; RR 0.841; 95% CI, 0.762-0.928; P = .001) compared with VKAs in overall cohort. Within the acute coronary syndrome group (n = 14,302), DOACs had lower stroke (12.3% vs 14.4%, RR 0.860; 95% CI, 0.791-0.935; P < .0001) and systemic embolism (3.1% vs 4%; RR 0.774; 95% CI, 0.651-0.919; P = .003) risks. For non-acute coronary syndrome group (n = 24,162), DOACs had lower stroke (11.4% vs 13.1%; RR 0.868; 95% CI, 0.811-0.929; P < .001) and major bleeding (4.8% vs 5.5%; RR 0.877; 95% CI, 0.787-0.977; P = .017) risks. No significant differences in all-cause mortality were observed across groups., Conclusion: DOACs demonstrated better safety and efficacy outcomes when compared with VKAs in left ventricular thrombus treatment, with or without recent acute coronary syndrome., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: "Real-life" data on cardiovascular management and clinical outcomes in patients with atrial fibrillation (AF) and hematologic malignancies are limited., Aim: To describe the clinical profile and incidence of cardiovascular events in this population., Methods: Data were obtained from the CANAC-FA Registry, an observational, multicenter and retrospective study. A review of the medical records of patients who had consulted for chronic lymphocytic leukemia (CLL) or multiple myeloma (MM) between 2017 and 2019 was conducted in five hospitals in Spain. Patients with atrial fibrillation (AF) were identified, and the initial visit during which specific treatment for the neoplasm was administered was considered the baseline visit. The follow-up period concluded in 2021. Events of interest included major bleeding, cardiovascular events (hospital admission for cardiovascular causes or cardiovascular death), and death from any cause., Results: A total of 7,793 patients were reviewed, of whom 1,189 (15%) had AF and 81 (1%) had AF and had initiated a specific hematological treatment within the previous year. Of these patients, 48 (59%) had MM and 33 (41%) had CLL. The mean values for the Charlson, CHA2DS2-VASc and HAS-BLED indices were 5.3 ± 1.7, 3.4 ± 1.5 and 2.4 ± 1.1, respectively. Anticoagulants were prescribed to 85% of patients, with a majority (42%) receiving direct anticoagulants. After a maximum follow-up period of 59 months, the incidences of events at 1, 2 and 3 years of follow-up were: 1.2±1.2%, 1.2±1.2 and 3.5±2.5% for major bleeding; 11.6±3.7%, 11.6±3.7 and 17.2±5.3% for cardiovascular events; and 27.6±5.0%, 41.5±6.3 and 51.3±6.9% for all-cause mortality., Conclusions: The incidence of cardiovascular events was high in this population, suggesting the need to implement more effective preventive strategies., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024. Published by Elsevier Inc.)

Background: Thrombolysis is recommended in the setting of massive pulmonary embolism (PE) for reperfusion of vessels but carries a serious concern for increased bleed risk. In October 2022, our institution adopted tenecteplase as the formulary thrombolytic. Previous literature is unclear regarding the bleed risk of tenecteplase in massive PE, and no study has yet compared safety outcomes with the current standard of care, alteplase., Objective: The objective of this study was to compare the incidence of bleeding with tenecteplase versus alteplase in massive PE patients., Methods: This was a retrospective, observational cohort study that included adults who received tenecteplase or alteplase for massive PE. The primary outcome was major bleeding as defined by the International Society on Thrombosis and Hemostasis (ISTH). Secondary outcomes included incidence of symptomatic intracranial hemorrhage (ICH), in-hospital mortality, administration of reversal agents, and length of stay., Results: A total of 44 patients met inclusion criteria with 20 patients in the alteplase cohort and 24 in the tenecteplase cohort. Seventeen percent of tenecteplase patients compared with 5% of alteplase patients experienced bleeding. The mortality rate was 83% vs 75%, respectively. In addition, 1 patient in the tenecteplase cohort experienced a symptomatic ICH and 2 patients required initiation of massive transfusion protocol., Conclusion and Relevance: Although this study was limited in sample size, these results suggest that there may be reason for concern of higher bleeding rates in patients treated with tenecteplase in the setting of massive PE., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

There are limited data about the clinical benefits and harm of oral anticoagulants (OACs) for stroke prevention in patients with atrial fibrillation (AF) and chronic kidney disease using CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine equation for glomerular filtration rate (GFR) estimation in nuanced GFR stratification. We conducted a retrospective study in 12 centers in China and included 9,510 patients with AF. We grouped patients into the following estimated GFR (eGFR) categories: ≥60 (n = 7,616), 45 to 59 (n = 1,139), 30 to 44 (n = 474), and <30 (n = 281) ml/min/1.73 m 2 . Logistic regression was used to the compare risks of major bleeding, minor bleeding, total bleeding, thrombosis, and all-cause deaths in patients with AF with eGFR 45 to 59, 30 to 44, <30 ml/min/1.73 m 2 , and ≥60 ml/min/1.73 m 2 after taking OACs. Patients with AF treated with OACs with eGFR 45 to 59, 30 to 44, and <30 ml/min/1.73 m 2 had a significantly increased risk of all-cause deaths compared with eGFR ≥60 ml/min/1.73 m 2 (adjusted odds ratio [aOR] 1.326, 95% confidence interval [CI] 1.049 to 1.665, p = 0.016; aOR 1.634, 95% CI 1.197 to 2.200, p = 0.002; aOR 2.492, 95% CI 1.766 to 3.471, p <0.001; respectively). Higher eGFR was associated with a significantly lower risk of all-cause deaths (aOR 0.990, 95% CI 0.986 to 0.994, p <0.001) and major bleeding (aOR 0.988, 95% CI 0.979 to 0.998, p = 0.018). Direct OACs remarkably reduced risk of major bleeding in those with eGFR 30 to 44 ml/min/1.73 m 2 compared with warfarin. In conclusion, in patients with AF treated with OACs, patients with eGFR 45 to 59, 30 to 44, and <30 ml/min/1.73 m 2 had a significantly increased risk of all-cause deaths compared with eGFR ≥60 ml/min/1.73 m 2 , and the risk of all-cause deaths increased with decreasing eGFR. Direct OACs are at least safe alternatives to warfarin in patients with AF with eGFR 30 to 44 ml/min/1.73 m 2 ., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Current guidelines provide no clear recommendations for managing new-onset atrial fibrillation in critical illness, particularly with respect to anticoagulant use. This retrospective study aimed to evaluate the efficacy and safety of anticoagulants in such patients., Materials and Methods: Patients in the intensive care unit with new-onset atrial fibrillation were recruited during the period January 1, 2021, to June 30, 2022. Ischemic stroke and bleeding were considered primary outcomes, and in-hospital death was considered the secondary outcome. Hazard ratios for outcomes were determined using the Cox proportional hazard model., Results: A total of 92 patients were included in the study of which 29 were anticoagulant users and 63 non-users. No significant differences were observed on the risk of ischemic stroke (HR, 3.46; 95% CI, 0.22 - 55.8, p = 0.38) and bleeding (HR, 1.07; 95% CI, 0.52 - 2.23, p = 0.85), but anticoagulant use was associated with a significantly decreased risk of in-hospital death (HR, 0.43; 95% CI, 0.19 - 0.97, p = 0.04)., Conclusion: Anticoagulant use in critically ill patients with new-onset atrial fibrillation did not increase the risk of bleeding and ischemic stroke but significantly reduced in-hospital deaths. These findings need confirmation in a randomized controlled trial.

Background: Warfarin interacts with antibacterials to prolong the prothrombin time international normalized ratio (PT-INR) and increase the risk of bleeding. Patients initiating warfarin therapy often undergo precise dosage adjustments; however, the clinical implications of these interactions with antibacterials remain unclear. This study aimed to clarify the effect of antibacterials on PT-INR during the warfarin induction phase., Methods: This was a retrospective, observational study. Patients who were newly treated with warfarin after cardiovascular surgery were included. The primary endpoint was the comparison of the maximum PT-INR and time in therapeutic range (TTR) after warfarin initiation between the antibacterial-treated (ABx) and non-treated (non-ABx) groups., Results: The maximum PT-INR was significantly higher in the ABx group (which included β-lactams, glycopeptides, quinolones, tetracyclines, and aminoglycosides) than in the non-ABx group (median [interquartile range] 2.37 [2.03-2.71] vs. 2.08 [1.93-2.33]; P = 0.005); however, the TTR did not differ significantly (65% [44-76] vs. 71% [43-85]; P = 0.150). The odds ratio for maximum PT-INR > 2.6 with antimicrobial therapy was 2.51 (95% confidence interval 1.21-5.21)., Discussion: Antibacterial therapy was a risk factor for a maximum PT-INR >2.6. However, there was no association with the TTR, which is a marker of good outcomes. This was due to the strict warfarin dosing regimen according to the algorithm, which immediately and appropriately adjusted for PT-INR overexpansion., Conclusions: Antibacterials have been suggested to increase PT-INR during the induction phase of warfarin. However, with strict dose adjustments, the clinical impact on the PT-INR and TTR is likely limited., Competing Interests: Declarations. Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Conflict of interest: Kyohei Sugiyama, Keita Hirai, Masato Tsutsumi, Shota Furuya, and Kunihiko Itoh declare that they have no potential conflicts of interest that might be relevant to the contents of this manuscript. Data availability statement: The data that support the findings of this study are available from the corresponding author upon reasonable request. Ethics approval: This study was conducted with the approval of the ethics committee of Shizuoka General Hospital (approved number: SGHIRB#2021077). Code availability: Not applicable. Consent to participate: Not applicable. Consent for publication: Not applicable. Author contributions: K.S. and K.H. designed the study. K.S., M.T., S.F. and K.I. performed the experiments. K.S. and K.H. analyzed the data. K.S. and K.H. wrote the manuscript. All the authors read and approved the final manuscript., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

No existing studies compare oral anticoagulants to treat heparin-induced thrombocytopenia with or without thrombosis (HIT/HITT). This retrospective study evaluated thrombotic and bleeding outcomes in adults treated for HIT/HITT with a direct oral anticoagulant (DOAC) or warfarin between 2012 and 2023 within the Ochsner Health System. Patients with mechanical heart valves, valvular atrial fibrillation, antiphospholipid syndrome, active malignancy, or venous thromboembolism (VTE) within the previous 6 months were excluded. The primary outcome was a composite of new or progressive VTE or arterial thromboembolism. Secondary outcomes included major and clinically relevant non-major bleeding, duration of hospitalization, time to platelet recovery, and incidence of skin necrosis, gangrene, and amputation. Forty-nine patients receiving a DOAC and 30 patients receiving warfarin were included. Baseline characteristics were similar between cohorts. There were non-statistically significant increased rates of both the primary outcome (8.9% vs. 4.3%, p = 0.65) and the composite bleeding outcome (32.7% vs. 23.3%, p = 0.37) in the DOAC cohort. Larger, prospective studies are needed to confirm these findings., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Thromboembolic events and atrial fibrillation are common among kidney transplant recipients (KTRs), and these conditions typically require anticoagulation. Traditionally, vitamin K antagonists were used for management, but the use of direct oral anticoagulants (DOACs) has increased in KTRs. In the general population, DOACs are recommended over warfarin, but the applicability of these recommendations to KTRs is unclear because of risk-benefit concerns. There is some hesitancy to use DOACs in KTRs because of their dependence on renal clearance for elimination, potential drug-drug interactions, and limited data. To date, studies of DOACs in KTRs have demonstrated that they are efficient in thromboembolic events, major bleeding is rare, and drug-drug interactions appear rare. However, no guidance yet exists about the use of DOACs, reversal of DOAC action, and the pre- and post-kidney transplant management of DOACs in KTRs, and the evidence base is scarce. Thus, decisions on DOAC use in KTRs are based on expert opinion and the resources and experiences of individual transplant centers. This review summarizes 10 published studies on the use of DOACs in 741 KTRs, evaluating the side effects, efficacy, drug-drug interactions, and perioperative management compared with those of 1320 KTRs using vitamin K antagonists. Although current data are limited, DOACs appear to be relatively safe and effective in KTRs, with some studies suggesting lower bleeding rates and better kidney function than with vitamin K antagonists. However, more research with larger patient groups is needed to draw definitive conclusions., Competing Interests: Declarations. Acknowledgement: Both figures were created in Biorender.com. Funding: No external funding was used in the preparation of this manuscript. Conflicts of interest: Baris Afsar, Rengin Elsurer Afsar, Yasar Caliskan, and Krista L Lentine declare that they have no potential conflicts of interest that might be relevant to the contents of this manuscript. Availability of data and materials: Data sharing is not applicable to this manuscript as no datasets were generated. Ethics approval: Not applicable. Author contribution: Data extraction, writing: BA. Writing: BA, YC: Reviewing and editing: KLL: reviewing, editing, and supervision. REA reviewing' editing and prepeartion of figures. Code availability: Not applicable. Consent to participate: Not applicable. Consent for publication: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Coronary artery ectasia (CAE) of the culprit infarct artery is a rare finding in patients with acute coronary syndrome (ACS). While anticoagulants have been suggested to reduce recurrent events, the optimal antithrombotic therapy remains unclear., Methods: OVER-TIME was an open label, exploratory, randomized controlled trial comparing dual antiplatelet therapy (DAPT; acetyl-salicylic-acid 100mg plus clopidogrel 75mg daily) versus single antiplatelet (SAPT, clopidogrel 75mg) plus DOAC (rivaroxaban 15mg) in patients with ACS and CAE. The study primary objectives were 1) the composite of cardiovascular death, recurrent MI and repeat revascularization and 2) total bleeding events (BARC 1-5) at 12 months. The secondary objective was fibrin clot lysis time (using turbidimetry)., Results: A total of 62 patients were randomized, 32 (51.6%) to receive DAPT and 30 (48.3%) to receive SAPT+DOAC. Patients were aged 55.5 years (±10.6) and mostly male (86.9%); STEMI was the most common presentation (83.8%). No statistically significant differences (HR 0.24, 95% CI 0.02-2.16, P = .20) in the risk of the primary endpoint were found; however, a numerically lower rate of recurrent MI (4 events - 12.5% - in the DAPT arm vs. 1 event - 3.3% in the SAPT+DOAC arm) was observed. The risk of bleeding events was not different HR 0.75 (95% CI 0.26-2.16, P = .59). A statistically significant reduction in fibrin clot lysis time (-24.7% reduction, P = .038) was observed in those randomized to SAPT+DOAC, but not in DAPT (-14.7% reduction, P = .25)., Conclusions: In this exploratory study including patients with ACS and CAE of the culprit artery, the use of rivaroxaban 15mg in addition to clopidogrel was not associated with a statistically lower risk of major adverse cardiovascular events; however, a lower rate of recurrent MI and a reduction in fibrin clot lysis time were observed. Future studies to address antithrombotic therapy in CAE are needed., Trial Registration: ClinicalTrials.gov ID NCT05233124, URL: https://clinicaltrials.gov/study/NCT05233124., Competing Interests: Declaration of competing interest DAG reports speaking fees for Abbott, Asofarma, Astra Zeneca, Boehringer Ingelheim, Bayer, Lundbeck, Novartis, Novo Nordisk, Silanes, Servier. Advisory board: Silanes, Servier, Novartis, Novo Nordisk. Research grants: Novartis, Novo Nordisk. RGN reports speaking fees for Novartis and Asofarma. JDSLM reports speaking fees from Bayer, Novartis and Novo Nordisk. AAM reports speaker fees from Asofarma, Astra Zeneca, Boehringer Ingelheim, Bayer, Novartis, Novo Nordisk. Rest of the authors do not report any relevant conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Vitamin K antagonists remain the mainstay of therapy in patients with left ventricular thrombus (LVT) because the efficacy of direct oral anticoagulants (DOACs) is not well-established. We performed a multicenter retrospective analysis of adults admitted between January 2015 and December 2021 and diagnosed with LVT to compare the safety and efficacy of warfarin versus DOACs. The primary outcome was thrombus resolution. Secondary outcomes included all-cause mortality, bleeding events, and stroke or systemic embolism. A total of 189 patients were included. The rate of thrombus resolution was similar in patients with LVT treated with DOACs compared with those treated with warfarin (DOACs 73.9%vs warfarin 68.5%, p = 0.489). In addition, all-cause mortality (DOACs 13.04% vs warfarin 9.79%, p = 0.583), bleeding events (DOACs 19.57% vs warfarin 13.99%, p = 0.361), and stroke or systemic embolism (DOACs 10.87% vs warfarin 15.38%, p = 0.446) were all similar in the 2 groups. In the propensity-matched group, 90 patients were included. Multivariate analysis showed no significant difference of using warfarin or DOACs on thrombus resolution (odds ratio [OR] 0.94, 95% confidence interval [CI] 0.858 to 1.029, p = 0.18), all-cause mortality (OR 1.032, 95% CI 0.906 to 1.176, p = 0.6354), bleeding events (OR 1.694, 95% CI 0.168 to 17.097, p = 0.655), or stroke or systemic embolism (OR 1.947, 95% CI 0.087 to 4.756, p = 0.6747). In conclusion, in our retrospective analysis, DOACs had similar efficacy and safety compared with warfarin in the treatment of LVT., Competing Interests: Declaration of competing interest The authors have no competing interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: This review aims to systematically summarize the available data on efficacy and safety of therapeutic enoxaparin in obese patients and to identify gaps to guide future research., Data Sources: Medline and Embase were systematically searched for eligible studies (last searched December 20, 2023). Studies were included if they reported on therapeutic dosing regimens, adverse bleeding, thrombotic outcomes, or antifactor Xa (AFXa) monitoring in obese adult patients., Study Selection and Data Extraction: The systematic review management tool Covidence was used to manage the study selection and data extraction process. The reference list from eligible studies was screened to determine any additional eligible studies., Data Synthesis: Sixteen studies were included in the analysis. Studies used a variety of doses, indications, and study designs making comparison difficult. Twelve studies reported the incidence of thrombotic events (median = 1.3% [interquartile range [IQR] = 0.3%-2.3%]) and all studies reported the incidence of bleeding events (median = 5.7% [IQR = 2.4%-14.5%]). Two of the 8 studies analyzing the influence of weight/body mass index (BMI) or dose per kg on AFXa levels reported statistically significant results. One study concluded that BMI did not affect achievement of target AFXa levels. However, the second study found that dosing using actual body weight was an independent predictor of supratherapeutic AFXa levels in the obese population., Relevance to Patient Care and Clinical Practice: This is the first comprehensive review with a focus on therapeutic dosing of enoxaparin in obesity and has been conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement. Seven of the included studies were published since 2018 indicating that new evidence on this topic is emerging., Conclusion: There was inadequate evidence to support an optimal dosing strategy in obese patients due to the heterogeneity of the studies. The AFXa monitoring may be appropriate to guide dosing in this population. Further research is required to determine a suitable dosing regimen., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

In this work, we describe an easy, simple, and cost-effective method to assess the proteolytic activity of snake venoms. The method is based on measuring the hydrolytic halo formed by gelatin radial hydrolysis following the incubation of venoms on a solid gelatin-agarose plate. Venoms from Bothrops (B.) alternatus, B. diporus, B. neuwiedi, B. jararaca, B. jararacussu, Crotalus atrox, and Trimeresurus albolabris were tested. A dose-response relationship was observed for each venom tested, with proteolytic capacity values, determined as GD (gelatinolytic dose, the dose causing a 15 mm hydrolytic halo) ranging from 21 to 222 μg. A correlation between hydrolysis and hemorrhagic activity in rat skin (minimal hemorrhagic dose) was found, with an r 2 value of 0.8774 (p < 0.0001). The venoms' hydrolytic activity was significantly, though not completely, inhibited by EDTA. This methodology was also deployed to assess venom neutralization by antivenoms on the hydrolytic activity of the different venoms, demonstrating its usefulness in evaluating antivenom neutralizing capacity. The method presented is simple, cheap and useful for preliminary screening of venom proteolytic activity and its inhibition and may also predict gross differences in hemorrhagic activity, contributing to the reduction of the number of animals used for these determinations., 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 Ltd. All rights reserved.)

Abstract: Current guidelines for treating vaccine-induced immune thrombotic thrombocytopenia (VITT) recommend nonheparin anticoagulants and IV immunoglobulin (IVIg). However, the efficacy of these treatments remains uncertain due to case studies involving small patient numbers, confounding factors (eg, concurrent treatments), and a lack of animal studies. A recent study proposed danaparoid and heparin as potential VITT therapies because of their ability to disrupt VITT IgG-platelet factor 4 (PF4) binding. Here, we examined the effects of various anticoagulants (including unfractionated [UF] heparin, danaparoid, bivalirudin, fondaparinux, and argatroban), IVIg, and the FcγRIIa receptor-blocking antibody, IV.3. Our investigation focused on VITT IgG-PF4 binding, platelet activation, thrombocytopenia, and thrombosis. Danaparoid, at therapeutic doses, was the sole anticoagulant that reduced VITT IgG-PF4 binding, verified by affinity-purified anti-PF4 VITT IgG. Although danaparoid and high-dose UF heparin (10 U/mL) inhibited platelet activation, none of the anticoagulants significantly affected thrombocytopenia in our VITT animal model and all prolonged bleeding time. IVIg and all anticoagulants except UF heparin protected the VITT mice from thrombosis. Direct FcγRIIa receptor inhibition with IV.3 antibody is an effective approach for managing both thrombosis and thrombocytopenia in the VITT mouse model. Our results underscore the necessity of animal model investigations to inform and better guide clinicians on treatment choices. This study provides compelling evidence for the development of FcγRIIa receptor blockers to prevent thrombosis in VITT and other FcγRIIa-related inflammatory disorders., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Current evidence indicates that dual antiplatelet therapy with aspirin plus a P2Y 12 inhibitor is essential for the prevention of thrombotic events after percutaneous coronary interventions. However, dual antiplatelet therapy is associated with increased bleeding which may outweigh the benefits. This has set the foundations for customizing antiplatelet treatments to the individual patient. However, bleeding and ischemic risks are often present in the same patient, making it difficult to achieve this balance. The fact that oral P2Y 12 inhibitors (clopidogrel, prasugrel, and ticagrelor) have diverse pharmacodynamic profiles that affect clinical outcomes supports the rationale for using platelet function and genetic testing to individualize antiplatelet treatment regimens. Indeed, up to one-third of patients treated with clopidogrel, but a minority of those treated with prasugrel or ticagrelor, exhibit high residual platelet reactivity resulting in an increased thrombotic risk. On the other hand, prasugrel and ticagrelor are frequently associated with low platelet reactivity and increased bleeding risk compared with clopidogrel without providing any additional reduction in ischemic events compared with patients who adequately respond to clopidogrel. The use of platelet function and genetic testing may allow for a guided selection of oral P2Y 12 inhibitors. However, the nonuniform results of randomized controlled trials have led guidelines to provide limited recommendations on the implementation of these tests in patients undergoing percutaneous coronary intervention. In light of recent advancements in the field, this consensus document by a panel of international experts fills in the guideline gap by providing updates on the latest evidence in the field as well as recommendations for clinical practice., Competing Interests: Funding Support and Author Disclosures Dr Angiolillo has received consulting fees or honoraria from Abbott, Amgen, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi, CSL Behring, Daiichi-Sankyo, Eli Lilly, Faraday, Haemonetics, Janssen, Merck, Novartis, Novo Nordisk, PhaseBio, PLx Pharma, Pfizer, and Sanofi; and his institution has received research grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Faraday, Gilead, Idorsia, Janssen, Matsutani Chemical Industry Co., Merck, Novartis, and the Scott R. MacKenzie Foundation. Dr Alexopoulos has received advisory board fees or honoraria from AstraZeneca, Bayer, Chiesi, and Pfizer; and institutional research grants from CSL Behring. Dr Aradi has received lecture fees from Amgen, AstraZeneca, Bayer AG, Biotronik, Boehringer, Egis, Krka, Medtronic, Novartis, Novo Nordisk, Pfizer, Richter Gedeon, and Vascular Venture. Dr Bhatt has served on the advisory board for Angiowave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, and Stasys; has served on the Board of Directors for American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock); has served as a consultant for Broadview Ventures, GlaxoSmithKline, Hims, SFJ, and Youngene; has served on Data Monitoring Committees for Acesion Pharma, Assistance Publique–Hôpitaux de Paris, the Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Cleveland Clinic, the Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi-Sankyo; for the ABILITY-DM trial, funded by Concept Medical; for ALLAY-HF, funded by Alleviant Medical), Novartis, the Population Health Research Institute, Rutgers University (for the National Institutes of Health–funded MINT trial); has served as a Data Monitoring Committee chair for Boston Scientific (PEITHO trial) and Contego Medical (PERFORMANCE 2); has received honoraria from American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol Myers Squibb clopidogrel litigation), the Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), the Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (American Heart Association lecture), Cowen and Company, the Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), JACC (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (continuing medical education steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and U.S. national co-leader, funded by Bayer), WebMD (continuing medical education steering committees), and Wiley (steering committee); has served as the Deputy Editor for Clinical Cardiology; owns a patent for Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women's Hospital who assigned to Lexicon; neither Dr Bhatt nor Brigham and Women's Hospital receives any income from this patent); has received research funding from Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89Bio; has received royalties from Elsevier (Editor, Braunwald’s Heart Disease); has served as a Site Co-Investigator for Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; has been a trustee of the American College of Cardiology; and has conducted unfunded research for FlowCo. Dr Bonello’s his institution received payment from INARI, Boston Scientific, Abbott, Biotronik, and Bristol Myers Squibb. Dr Capodanno has received payment as an individual for consulting fees or honoraria from Sanofi. Dr Cavallari has received research support from Werfen. Dr Cuisset has received consulting and lecture fees from Abbott Vascular, Boston Scientific, Edwards Lifesciences, Europa Organisation, Medtronic, Terumo, and Sanofi. Dr Ferreiro has received lecture honoraria from Eli Lilly, Daiichi-Sankyo, AstraZeneca, Pfizer, Abbott, Boehringer Ingelheim, Bristol Myers Squibb, Rovi, Terumo and Ferrer; consulting fees from AstraZeneca, Eli Lilly, Ferrer, Boston Scientific, Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Bristol Myers Squibb, and Biotronik; and research grants from AstraZeneca. Dr Franchi has received payment as an individual for consulting fees or honoraria from AstraZeneca; and institutional payments for grants from PLx Pharma and the Scott R. MacKenzie Foundation. Dr Geisler has received lecture honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Ferrer/Chiesi, Novartis, and Pfizer; consulting fees from AstraZeneca, Bristol Myers Squibb, Ferrer, Edwards Lifesciences, Haemonetics, and Pfizer; and research grants from Bayer, Bristol Myers Squibb/Pfizer, Ferrer/Chiesi, Medtronic, and Edwards Lifesciences. Dr Gibson has received grants from SCAD Alliance, Johnson & Johnson, Janssen, and CSL Behring; has received personal fees from Bayer, AstraZeneca (during the conduct of the study), Angel Medical Corporation, CSL Behring, Janssen, Johnson & Johnson, the Boston Clinical Research Institute, the Cardiovascular Research Foundation, Gilead Sciences, WebMD, UpToDate in Cardiovascular Medicine, Somahlution, Boston Scientific, the Duke Clinical Research Institute, Medtelligence, Microport, PERT Consortium, Caladrius Biosciences, CeleCor Therapeutics, Eidos Therapeutics, Microdrop, MD Magazine, the Society for Cardiovascular Angiography and Interventions, Revance Therapeutics, Pfizer, Dyad Medical, CytoSorbents, AMAG Pharmaceuticals, Bristol Myers Squibb, Amarin, PhaseBio, Bioclinica, Inari, MedImmune, PLx Pharma, Merck, Paratek, Anthos Therapeutics, PHRI, SmartMedics, EXCITE International ($0 received), Novo Nordisk, MedTrace, and the Cardiovascular Clinical Science Foundation; has received nonfinancial support from the Baim Institute; and owns equity in nference, Absolutys, and Dyad Medical. Dr Gorog has received institutional research grants from Bayer, AstraZeneca, Medtronic, and Werfen; and personal fees from Janssen, Bristol Myers Squibb, and Chiesi. Dr Gurbel has received consulting fees and/or honoraria from Bayer, Vectura/Otitopic, Janssen, Cleveland Clinic Foundation, Wolters Kluwer Pharma, Web MD Medscape, Baron and Budd, Premier Health Care Resource, Baim Institute, and Medforce; has received institutional research grants from Accriva Diagnostics, AstraZeneca, Bayer, Cronos, Janssen Pharmaceuticals Inc., Haemonetics, Hikari Dx, Idorisa, Labcorp Drug Development, Novartis, Prolocor, Recor Medical, Vectura Limited, and Zoll Medical Corporation; owns 2 patents (Detection of restenosis risk in patients issued and Assessment of cardiac health and thrombotic risk in a patient); has served as an expert witness in a lawsuit associated with Plavix. Dr Jeong has received honoraria for lectures from Daiichi-Sankyo, Sanofi, Han-mi Pharmaceuticals, and Daewoong Pharmaceuticals; and research grants or support from Samjin Pharmaceuticals, Hanmi Pharmaceuticals, Yuhan Pharmaceuticals, Biotronik Korea, and U and I Corporation. Dr Marcucci has received consulting fees or honoraria from Amgen, AstraZeneca, Bayer, Daiichi-Sankyo, Novartis, Sanofi, Viatris, and Werfen. Dr Siller-Matula has received speaker or consulting fees from AOP, Chiesi, Biosensors, Boston Scientific, P&F, Boehringer Ingelheim, and Daiichi-Sankyo not related to the submitted work. Dr Mehran has received institutional research payments from Abbott, Abiomed, Alleviant Medical, AM-Pharma, Amgen, Arena, AstraZeneca, Atricure, Bayer, Biosensors, Biotronik, Boston Scientific, Bristol Myers Squibb, CardiaWave, CeloNova, Chiesi, Concept Medical, CSL Behring, Cytosorbents, Daiichi-Sankyo, Element Science, Faraday, Humacyte, Idorsia Pharmaceuticals, Janssen, Medtronic, Novartis, OrbusNeich, PhaseBio, Philips, Pi-Cardia, RenalPro, Shockwave, Vivasure, and Zoll; has received personal fees from Cine-Med Research and WebMD; owns equity (<1%) in Applied Therapeutics, Elixir Medical, Stel, and ControlRad (via her spouse); has served on the Scientific Advisory Board for the American Medical Association, the American College of Cardiology (Board of Trustees Member), the Society for Cardiovascular Angiography and Interventions (Women in Innovations Committee Member), and JAMA (Associate Editor); and has served as faculty for the Cardiovascular Research Foundation (no fee). Dr Neumann has received consulting honoraria from Novartis and Meril; speaker honoraria from Boston Scientific, Amgen, Daiichi-Sankyo, and Meril; speaker honoraria paid to his institution from Bristol Myers Squibb/Pfizer, Daiichi-Sankyo, Boston Scientific, Siemens, and Amgen; and research grants paid to his institution from Boston Scientific and Abbott. Dr So has received consulting fees or honoraria from Abbott Vascular, AstraZeneca, Bayer, HLS Therapeutics, JAMP Pharma Corp, Medtronic, and DYFS; and received research grants from Aggredyne, Diapharma, Eli Lilly, Fujimori Kogyo, Roche Diagnostics, and Spartan Biosciences. Dr Stone has received speaker honoraria from Medtronic, Pulnovo, Infraredx, Abiomed, Amgen, and Boehringer Ingelheim; served as a consultant for Abbott, Daiichi-Sankyo, Ablative Solutions, CorFlow, Cardiomech, Robocath, Miracor, Vectorious, Abiomed, Valfix, Apollo Therapeutics, Elucid Bio, Cardiac Success, TherOx, HeartFlow, Neovasc, Ancora, Occlutech, Impulse Dynamics, Adona Medical, Millennia Biopharma, Oxitope, HighLife, Elixir, Remote Cardiac Enablement, and Aria; he owns equity/options in Cardiac Success, Ancora, Cagent, Applied Therapeutics, and Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Valfix, and Xenter; and his employer (Mount Sinai Hospital) has received research grants from Shockwave, Abbott, Abiomed, Bioventrix, Cardiovascular Systems Inc, Phillips, Biosense Webster, Vascular Dynamics, Pulnovo, and V-wave. Dr Storey has received institutional research grants/support from AstraZeneca and Cytosorbents; and personal fees from Alfasigma, AstraZeneca, Boehringer Ingelheim/Lilly, Chiesi, Cytosorbents, Daiichi-Sankyo, Idorsia, Novartis, Novo Nordisk, Pfizer, PhaseBio, and Tabuk. Dr Tantry has received honoraria from Wolters Kluwer Pharma. Dr ten Berg has received institutional research grants from ZonMw (Dutch Government) and Daiichi-Sankyo; has served on the advisory board CeleCor; and has received lecture and advisory board fees paid to his institution from AstraZeneca, Bristol Myers Squibb, and Pfizer. Dr Trenk has received honoraria for lectures from AstraZeneca, Daiichi-Sankyo, and Novartis; and consulting fees from Atriva, Daiichi-Sankyo, and Eleva. Dr Valgimigli has received personal fees from AstraZeneca, Terumo, Alvimedica/CID, Abbott Vascular, Daiichi-Sankyo, Bayer, CoreFLOW, Idorsia Pharmaceuticals Ltd, Universität Basel | Dept. Klinische Forschung, Bristol Myers Squibb SA/Janssen, Medscape, Biotronik, Novartis, and Vesalio, outside the submitted work; and grants from Terumo, outside the submitted work. Dr Waksman has served on advisory boards for Abbott Vascular, Boston Scientific, J Valve, Medtronic Inc, Philips IGT, and Pi-Cardia Ltd.; has served as a consultant for Abbott Vascular, Biotronik, Boston Scientific, CardioMed LLC, Cordis, Medtronic Inc, Philips IGT, Pi-Cardia Ltd., Swiss Interventional Systems/SIS Medical AG, Transmural Systems Inc., and Venous MedTech; has received institutional grant support from Amgen, Biotronik, Boston Scientific, Chiesi, Medtronic Inc, and Philips IGT; and is an investor in MedAlliance, Pi-Cardia Ltd., and Transmural Systems. Dr Sibbing has received speaker fees and fees for advisory board activities from Bayer, Sanofi, and Daiichi-Sankyo. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Abbreviated antiplatelet therapy (APT) reduces bleeding without increasing ischemic events in largely unselected high bleeding risk (HBR) patients undergoing percutaneous coronary intervention (PCI). Diabetes mellitus (DM) is associated with higher ischemic risk, and its impact on the safety and effectiveness of abbreviated APT in HBR PCI patients remains unknown., Objectives: This study sought to investigate the comparative effectiveness of abbreviated (1 month) vs standard (≥3 months) APT in HBR patients with and without DM after biodegradable polymer sirolimus-eluting coronary stent implantation., Methods: This was a prespecified analysis from the MASTER DAPT (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With a Abbreviated Versus Prolonged DAPT Regimen) trial, which randomized 4,579 HBR patients (1,538 [34%] with DM) to abbreviated (n = 2,295) or standard (n = 2,284) APT. The coprimary outcomes were net adverse clinical events (NACEs; composite of all-cause death, myocardial infarction, stroke, and major bleeding), major adverse cardiac or cerebral events (MACCEs; all-cause death, myocardial infarction, and stroke), and major or clinically relevant nonmajor bleeding at 11 months., Results: HBR patients with DM had higher risks of MACCEs (HR: 1.28; 95% CI: 1.00-1.63) and similar net adverse or bleeding events compared with nondiabetic subjects. Abbreviated compared with standard APT was associated with similar NACEs and MACCEs (P interaction  = 0.47 and 0.59, respectively) and reduced major or clinically relevant nonmajor bleeding (P interaction  = 0.55) irrespective of diabetes status., Conclusions: MACCE and NACE rates were similar, and bleeding rates were lower with abbreviated APT in patients with or without diabetes. Therefore, diabetes status did not modify the treatment effects of abbreviated vs standard APT in HBR patients after biodegradable polymer sirolimus-eluting coronary stent implantation. (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With a Abbreviated Versus Prolonged DAPT Regimen [MASTER DAPT]; NCT03023020)., Competing Interests: Funding Support and Author Disclosures The study was sponsored by the European Cardiovascular Research Institute, a nonprofit organization, and received grant support from Terumo. Dr Roffi has received institutional research grants from Cordis, Boston Scientific, Medtronic, Biotronik, and Terumo. Drs Heg and Chalkou are employed by the Department of Clinical Research, University of Bern, which has a staff policy of not accepting honoraria or consultancy fees; however, DCR is involved in the design, conduct, or analysis of clinical studies funded by not-for-profit and for-profit organizations. In particular, pharmaceutical and medical device companies provide direct funding to some of these studies. Dr Chevalier is a minor shareholder of CERC. Dr Morice is a minor shareholder of Electroducer and Basecamps and a shareholder and CEO of CERC. Dr Vranckx has received personal fees from Bayer, Daiichi-Sankyo, and CLS Behring, outside the submitted work. Dr Windecker has received research, travel, or educational grants to the institution without personal remuneration from Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Braun, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardinal Health, CardioValve, Cordis Medical, Corflow Therapeutics, CSL Behring, Daiichi-Sankyo, Edwards Lifesciences, Farapulse Inc, Fumedica, Guerbet, Idorsia, Inari Medical, InfraRedx, Janssen-Cilag, Johnson & Johnson, Medalliance, Medicure, Medtronic, Merck Sharp & Dohme, Miracor Medical, MonarQ, Novartis, Novo Nordisk, Organon, OrPha Suisse, Pharming Tech, Pfizer, Polares, Regeneron, Sanofi, Servier, Sinomed, Terumo, Vifor, V-Wave; has served as an advisory board member and/or member of the steering/executive group of trials funded by Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Boston Scientific, Biotronik, Bristol Myers Squibb, Edwards Lifesciences, MedAlliance, Medtronic, Novartis, Polares, Recardio, Sinomed, Terumo, and V-Wave with payments to the institution but no personal payments; and is a member of the steering/executive committee group of several investigator-initiated trials that receive funding by industry without impact on his personal remuneration. Dr Smits has received personal consulting or speaker fees from Terumo, Abiomed, and Opsense; has received grants and personal consulting fees from Abbott Vascular, Microport, and Daiichi-Sankyo; and has received grants from SMT. Dr Valgimigli has received grants and/or personal fees from AstraZeneca, Terumo, Alvimedica/CID, Abbott Vascular, Daiichi-Sankyo, Bayer, CoreFLOW, Idorsia Pharmaceuticals Ltd, Universität Basel Department Klinische Forschung, Vifor, Bristol Myers Squibb SA, Biotronik, Boston Scientific, Medtronic, Vesalio, Novartis, Chiesi, and PhaseBio, outside the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The Direct Oral Anticoagulant (DOAC) Score can predict bleeding risk in patients with atrial fibrillation taking DOACs; however, it lacks external validation. Therefore, this study aimed to assess the association between the DOAC Score and bleeding events in patients with atrial fibrillation who underwent transcatheter aortic valve replacement., Methods and Results: This retrospective multicenter cohort study included patients with atrial fibrillation who underwent transcatheter aortic valve replacement, as registered in a Japanese multicenter registry. The primary end point was the incidence of bleeding. Patients were categorized based on their DOAC Score: low and moderate- (≤7 points), high- (8-9 points), and very high-risk (≥10 points) groups. Among 1230 patients (mean age 84.6±5.1 years; 457 men), 465 (37.8%) received a vitamin K antagonist, and the remaining patients received DOACs. The low and moderate-, high-, and very high-risk groups included 380 (30.1%), 497 (40.4%), and 353 patients (28.7%), respectively. The 3-year cumulative incidence of all bleeding events was significantly different among the 3 groups (low and moderate risk: 6.6%, high risk: 6.9%, and very high risk: 14.0%; P <0.01). Multivariable Cox regression analysis revealed that significant increments in the DOAC Score were associated with a risk of all bleeding events at 3 years in the overall cohort (hazard ratio [HR], 1.22 [95% CI, 1.08-1.38]; P <0.01), in the DOAC cohort (HR, 1.20 [95% CI, 1.01-1.42]; P =0.04), and in the vitamin K antagonist cohort (HR, 1.25 [95% CI, 1.04-1.50]; P =0.02)., Conclusions: The DOAC Score was significantly associated with bleeding events in patients with atrial fibrillation after transcatheter aortic valve replacement, aiding in clinical decision-making for anticoagulant management., Registration: URL: https://center6.umin.ac.jp/cgi-open-bin/ctr&#95;e/ctr&#95;view.cgi?recptno=R000023585; Unique identifier: UMIN000020423.

Background: Anticoagulation in atrial fibrillation (AF) increases the risk of major bleeding. No predictive model has hitherto provided estimates of the absolute risk for individual patients., Aim: To predict the individual 1-year risk of major bleeding in patients with AF taking anticoagulants and evaluate the importance of individual risk factors., Design: A nationwide register-based cohort study., Participants: Danish patients with first-time non-valvular AF who redeemed anticoagulants within 7 days after diagnosis., Method: The individual absolute risk of major bleeding was estimated from a logistic regression model (the Calculator of Absolute Bleeding Risk/CABS model) utilising the same risk factors as HAS-BLED, except allowing non-linear age effects, and allowing effect modification of all factors according to history of bleeding. The logistic regression was assessed in term of discrimination using the Area Under the ROC curve (AUC) and calibration., Results: Among 76,102 patients with AF redeeming anticoagulants, 2,406 suffered a major bleeding within 1 year. History of bleeding was the strongest predictor, and age significantly modified the risk. The CABS model superseded HAS-BLED score with regards to discrimination (AUC 0.646 vs 0.615, p<0.001) and calibrated well. A typical male patient was 70-years old without any risk factors and he had a 1-year bleeding risk of 1.4% (1.2; 1.6) while a typical female patient was 73-years old, had hypertension and a 1-year bleeding risk of 2.2% (1.9;2.6)., Conclusion: We propose CABS as a tool for prediction of individual absolute risks of major bleeding in patients with AF taking anticoagulant. The predicted absolute risk can be used for patient counselling., Competing Interests: CTP is supported by grants from Novo Nordic and Bayer. All other authors declared no conflict of interest. There was no funding for the study., (Copyright: © 2024 Toft-Petersen 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.)

Background: COVID-19 pandemics increases venous thromboembolism (VTE) risk during hospitalization, despite prophylactic anticoagulation. Limited radiological diagnosis in pandemic requires a guided protocol for anticoagulant adjustment., Methods: This retrospective cohort study was conducted at a single center as part of a quality improvement program evaluating the efficacy and safety of anticoagulation protocols. The study focused on implementing a guideline for anticoagulant dosing protocol based on dynamic changes in D-dimer levels in COVID-19 hospitalized patients. The dosing guideline allowed for dose escalation from standard prophylactic levels to escalated prophylactic or therapeutic levels, depending on the patient's risk profile for VTE. The primary endpoints included in-hospital survival comparing between fix and dynamic adjustment treatment groups. Secondary endpoints encompassed major and clinically relevant non-major bleeding (CRNMB) events, incidence of breakthrough thrombosis, length of hospitalization and ICU stay, days of mechanical ventilator use, and survival duration., Findings: Among the 260 COVID-19-infected patients hospitalized between March 15th and June 15th, 2020. The patients received fixed anticoagulant dosage in 188, 72.3%) patients, while 72 (27.7%) were up-titrated according to the protocol. In-hospital survival at 30 days demonstrated superiority among patients whose anticoagulation was up-titrated to either escalated prophylactic or therapeutic (80.2%) compared to receiving fixed anticoagulant dosage (51.3%) (p=0.01). Bleeding events were significantly higher in up-titrate group (12.5%) compared to fixed anticoagulant dosage group (2.13%). Most of them are CRNMB., Conclusion: A dynamic, D-dimer-based dose escalation of anticoagulation for hospitalized patients with COVID-19 holds promise in improving in-hospital mortality rates without a significant increase in fatal bleeding events., Competing Interests: Competing interests: Declaration of interests ☒ 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. ☒The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Casey O’Connell: consulting fee from AbbVie Inc. Advisory Board Janice Liebler: Grants or contracts from Immunexpress, St. Michaels Hospital, Toronto, Canada, CDC Foundation No conflict of interest for other authors., (Copyright: © 2024 Bhoopat L et al.)

The OCEANIC-AF trial was terminated early due to inferiority of asundexian compared with apixaban for the prevention of stroke and systemic embolism in patients with atrial fibrillation. 1 However, the promisingly low bleeding rates support continued exploration of factor XIa inhibitors. Future efforts should focus on achieving greater factor XIa inhibition and identifying patient populations that may benefit most from these therapies., Competing Interests: Declaration of interests L.P. served as an investigator in the OCEANIC-AF trial and serves as an investigator in the OCEANIC-STROKE trial. G.T. served as a local principal investigator in the OCEANIC-AF trial and serves as a national principal investigator in the OCEANIC-STROKE trial. He also serves on the Steering Committee of the OCEANIC-STROKE trial., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Obesity and underweight are a growing health problem worldwide and a challenge for clinicians concerning antithrombotic therapy, due to the associated risks of thrombosis and/or bleeding. This clinical consensus statement updates a previous one published in 2018, by reviewing the most recent evidence on antithrombotic drugs based on body size categories according to the World Health Organization classification. The document focuses mostly on individuals at the extremes of body weight, i.e. underweight and moderate-to-morbid obesity, who require antithrombotic drugs, according to current guidelines, for the treatment or prevention of cardiovascular diseases or venous thromboembolism. Managing antithrombotic therapy or thromboprophylaxis in these individuals is challenging, due to profound changes in body composition, metabolism and organ function, and altered drug pharmacokinetics and pharmacodynamics, as well as weak or no evidence from clinical trials. The document also includes artificial intelligence simulations derived from in silico pharmacokinetic/pharmacodynamic models, which can mimic the pharmacokinetic changes and help identify optimal regimens of antithrombotic drugs for severely underweight or severely obese individuals. Further, bariatric surgery in morbidly obese subjects is frequently performed worldwide. Bariatric surgery causes specific and additional changes in metabolism and gastrointestinal anatomy, depending on the type of the procedure, which can also impact the pharmacokinetics of antithrombotic drugs and their management. Based on existing literature, the document provides consensus statements on optimizing antithrombotic drug management for underweight and all classes of obese patients, while highlighting the current gaps in knowledge in these complex clinical settings, which require personalized medicine and precision pharmacology., (© 2024 the European Society of Cardiology.)

Venom-induced hemorrhage analysis usually is performed by Minimum Hemorrhagic Dose (MHD), however a similar method can be used to compare venoms with fewer laboratory animals. Our work compared the MHD of five different venoms, with the size of hemorrhagic spot, finding good correlations in the results. Considering the 3Rs principle, we propose the use of the hemorrhagic spot method to compare hemorrhagic activity of snake venoms, rather than using the MHD method, since the first one needs 5 times less animals than the other., 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 Ltd. All rights reserved.)

Background: P2Y12 inhibitor monotherapy after a short course of dual antiplatelet therapy (DAPT) may balance ischaemic and bleeding risks in patients with acute coronary syndrome (ACS). However, it remains uncertain how different P2Y12 inhibitors used as monotherapy affect outcomes., Methods and Results: Randomized controlled trials comparing P2Y12 inhibitor monotherapy after a short course of DAPT (≤3 months) vs. 12-month DAPT in ACS were included. The primary endpoint was major adverse cardiovascular events (MACE). All analyses included an interaction term for the P2Y12 inhibitor used as monotherapy. Trial sequential analyses were run to explore whether the effect estimate of each outcome may be affected by further studies. Seven trials encompassing 27 284 ACS patients were included. Compared with 12-month DAPT, P2Y12 inhibitor monotherapy after a short course of DAPT was associated with no difference in MACE [odds ratio (OR) 0.92, 95% confidence interval (CI) 0.76-1.12] and a significant reduction in net adverse clinical events (NACE) (OR 0.75; 95% CI 0.60-0.94), any bleeding (OR 0.54, 95% CI 0.43-0.66), and major bleeding (OR 0.47, 95% CI 0.37-0.60). Significant interactions for subgroup difference between ticagrelor and clopidogrel monotherapy were found for MACE (Pint = 0.016), all-cause death (Pint = 0.042), NACE (Pint = 0.018), and myocardial infarction (Pint = 0.028). Trial sequential analysis showed conclusive evidence of improved NACE with ticagrelor, but not with clopidogrel monotherapy, compared with standard DAPT., Conclusions: In patients with ACS, P2Y12 inhibitor monotherapy after short DAPT halves bleeding without increasing ischaemic events compared with standard DAPT. Ticagrelor, but not clopidogrel monotherapy, reduced MACE, NACE, and mortality compared with standard DAPT, supporting its use after aspirin discontinuation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: This study investigated drug-drug interactions in patients with atrial fibrillation taking both a direct oral anticoagulant (DOAC) and an antiarrhythmic drug., Methods and Results: Using data from the National Health Insurance database (2012-2018), we identified 78 805 patients with atrial fibrillation on DOACs, with 24 142 taking amiodarone, 8631 taking propafenone, 2784 taking dronedarone, 297 taking flecainide, 177 taking sotalol, and 42 772 on DOACs alone. Patients with bradycardia, heart block, heart failure, mitral stenosis, prosthetic valves, or incomplete data were excluded. Propensity score matching compared those taking both DOACs and antiarrhythmic drugs with those on DOACs alone. There was an increased risk of major bleeding in patients concomitantly taking DOACs with amiodarone when compared with matched patients taking DOACs alone (hazard ratio [HR],1.13 [95% CI, 1.04-1.23]; P =0.0044), particularly in patients taking dabigatran (HR, 1.19 [95% CI, 1.03-1.38]; P =0.0175). No significant difference in bleeding risk was found for propafenone, dronedarone, flecainide, or sotalol. The small sample sizes in the flecainide and sotalol groups limit interpretation. Notably, intracranial bleeding risk was higher in patients on DOACs and amiodarone, regardless of age. Additionally, patients <80 years old taking dabigatran with amiodarone or propafenone had a higher risk of gastrointestinal bleeding., Conclusions: Concomitant use of DOACs with amiodarone, but not dronedarone or propafenone, increases the risk of major bleeding, particularly intracranial bleeding. This study provides new evidence to guide clinicians to tailor concomitant anticoagulation and antiarrhythmic therapy for patients with atrial fibrillation.

Objectives: Evidence of the optimal antiplatelet therapy for elderly patients who had a stroke is limited, especially those elder than 80 years. This study aimed to explore the efficacy and safety of dual antiplatelet therapy (DAPT) in old-old patients compared with younger patients in the ticagrelor or Clopidogrel with aspirin in High-risk patients with Acute Non-disabling Cerebrovascular Events-II (CHANCE-2) trial., Methods: CHANCE-2 was a randomised, double-blind, placebo-controlled trial in China involving patients with high-risk transient ischaemic attack or minor stroke with CYP2C19 loss-of-function alleles. In our substudy, all enrolled patients were stratified by age: old-old (≥80 years), young-old (65-80 years) and younger (<65 years). The primary outcomes were stroke recurrence and moderate to severe bleeding within 90 days, respectively., Results: Of all the 6412 patients, 406 (6.3%) were old-old, 2755 (43.0%) were young-old and 3251 (50.7%) were younger. Old-old patients were associated with higher composite vascular events (HR 1.41, 95% CI 1.00 to 1.98, p=0.048), disabling stroke (OR 2.43, 95% CI 1.52 to 3.88, p=0.0002), severe or moderate bleeding (HR 8.40, 95% CI 1.95 to 36.21, p=0.004) and mortality (HR 7.56, 95% CI 2.23 to 25.70, p=0.001) within 90 days. Ticagrelor-aspirin group was associated with lower risks of stroke recurrence within 90 days in younger patients (HR 0.68, 95% CI 0.51 to 0.91, p=0.008), which was no differences in old-old patients., Conclusion: Elderly patients aged over 80 in CHANCE-2 trial had higher risks of composite vascular events, disabling stroke, severe or moderate bleeding and mortality within 90 days. Genotype-guided DAPT might not be as effective in old-old patients as in younger ones., Trial Registration Number: NCT04078737., Competing Interests: Competing interests: SCJ reports compensation from Everest CRO for data and safety monitoring services and compensation from AstraZeneca AB for consultant services. PMB reports grants from Alzheimer’s Society; compensation from DiaMedica for consultant services; compensation from Sanofi for consultant services; compensation from Phagenesis for consultant services; compensation from Moleac for consultant services; grants from British Heart Foundation; and grants from NIHR. YoW reports grants from Amgen; compensation from SANOFI-AVENTIS US for consultant services; grants from SANOFI-AVENTIS US; and grants from AstraZeneca. The other authors report no conflicts., (© 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.)

Intravenous thrombolysis is not recommended in anticoagulated patients receiving direct oral anticoagulants (DOACs) and a recent intake within the last 48 hours in US and European guidelines. However, three observational studies now suggest safety of thrombolysis in patients with recent intake of DOACs, and thus support previous experimental data. In this perspective, the current evidence and practical consequences are discussed., Competing Interests: Competing interests: JCP has received consultation fees and travel expenses from Akcea, Bayer, Boehringer Ingelheim, Daiichi Sankyo and BMS/Pfizer, outside the submitted work. TRM reports grants from Bangerter-Rhyner Foundation. YX has received a research grant from the National Institute on Aging, American Heart Association and Genentech, and honorarium from Boehringer Ingelheim. DJS is on the advisory board of Bayer Switzerland and Portola/Alexion. He reports research funding from the Swiss National Science Foundation, Swiss Heart Foundation, Bangerter-Rhyner Foundation, Bayer Foundation and Portola/Alexion. All other authors report no competing interests., (© 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.)

Despite the use of conventional dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI), the risk of adverse events remains high among patients with increased thrombotic risk. Until recently, the optimal antiplatelet strategy to balance the ischaemic and bleeding risks in patients who are undergoing complex high-risk PCI has been unclear. The TAILored Versus COnventional AntithRombotic StratEgy IntenDed for Complex HIgh-Risk PCI (TAILORED-CHIP) trial is an investigator-initiated, multicentre, prospective randomised trial to evaluate the efficacy and safety of a time-dependent tailored antiplatelet therapy with an early (<6 months post-PCI) escalation (low-dose ticagrelor at 60 mg twice daily plus aspirin) and a late (>6 months post-PCI) de-escalation (clopidogrel monotherapy) in patients undergoing complex high-risk PCI as compared with standard DAPT (clopidogrel plus aspirin for 12 months). Eligible patients had to have at least one high-risk anatomical or procedural feature or clinical characteristic associated with an increased risk of ischaemic or thrombotic events. The primary endpoint was the net clinical outcome, a composite of death from any cause, myocardial infarction, stroke, stent thrombosis, urgent revascularisation, or clinically relevant bleeding (Bleeding Academic Research Consortium type 2, 3, or 5) at 12 months after randomisation. (ClinicalTrials.gov: NCT03465644).

Background:  Real-world data on clinical characteristics and outcomes related to the use of different direct oral anticoagulants (DOACs) for cancer-associated venous thromboembolism (VTE) is lacking., Methods:  The COMMAND VTE Registry-2 is a multicenter registry enrolling 5,197 consecutive patients with acute symptomatic VTE from 31 centers in Japan from January 2015 to August 2020. Our study population comprised 1,197 patients with active cancer who were divided into the edoxaban ( N  = 643, 54%), rivaroxaban ( N  = 297, 25%), and apixaban ( N  = 257, 22%) groups., Results:  The cumulative 5-year incidence of recurrent VTE (9.3, 10.2, and 8.5%, respectively, p  = 0.82) and all-cause death (67.5, 66.8, and 63.8%, respectively, p  = 0.22) did not differ among the groups. Despite adjusting for confounders, the risks of recurrent VTE and all-cause death did not differ significantly among the groups. The cumulative 5-year incidence of major and clinically relevant bleeding was significantly lower in the rivaroxaban group than those in the other groups (22.6, 14.0, and 22.8%, p  = 0.04; and 37.6, 26.8, and 38.3%, p  = 0.01, respectively). After adjusting for confounders, in the rivaroxaban group, the risk for major bleeding was numerically lower (hazard ratio [HR]: 0.65, 95% confidence interval [CI]: 0.40-1.01) and that of clinically relevant all bleeding was significantly lower (HR: 0.67, 95% CI: 0.48-0.92) than those in the edoxaban group., Conclusion:  The risks of recurrent VTE and all-cause death did not differ significantly among the different DOACs ; however, the risk of bleeding events could differ, with a potentially lower risk of bleeding with rivaroxaban., Competing Interests: Y.Y. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi-Sankyo, and grant support from Bayer Healthcare and Daiichi-Sankyo. T.M. reports lecturer's fees from Bristol-Myers Squibb, Daiichi Sankyo, Japan Lifeline, Kowa, Kyocera, Novartis, and Toray; manuscript fees from Bristol-Myers Squibb and Kowa; advisory board for Sanofi. Y.N. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi-Sankyo. K.K. received lecture fees from Bristol-Myers Squibb, Pfizer, and Daiichi-Sankyo. N.I. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, and Daiichi-Sankyo. S.I. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, and Daiichi-Sankyo. Y.O. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi-Sankyo, and research funds from Bayer Healthcare and Daiichi-Sankyo. K.T. received significant research grant from AMI Co., Ltd., Bayer Yakuhin, Ltd., Bristol-Myers K.K., EA Pharma Co., Ltd., MOCHIDA PHARMACEUTICAL CO., LTD., and scholarship fund from AMI Co., Ltd., Bayer Yakuhin, Ltd., Boehringer Ingelheim Japan, Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Edwards Lifesciences Corporation, Johnson & Johnson K.K., ONO PHARMACEUTICAL CO., LTD., Otsuka Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and honoraria from Amgen K.K., Bayer Yakuhin, Ltd., Daiichi Sankyo Co., Ltd., Kowa Pharmaceutical Co. Ltd., Novartis Pharma K.K., Otsuka Pharmaceutical Co., Ltd., Pfizer Japan Inc., and belongs to the endowed departments donated by Abbott Japan Co., Ltd., Boston Scientific Japan K.K., Fides-one, Inc., GM Medical Co., Ltd., ITI Co., Ltd., Kaneka Medix Co., Ltd., NIPRO CORPORATION, TERUMO Co, Ltd., Abbott Medical Co., Ltd., Cardinal Health Japan, Fukuda Denshi Co., Ltd., Japan Lifeline Co., Ltd., Medical Appliance Co., Ltd., Medtronic Japan Co., Ltd. All other authors have reported that they have no relationships relevant to the contents of this article to disclose., (Thieme. All rights reserved.)

Diffuse alveolar hemorrhage (DAH) is a form of hemoptysis caused by disruption of the alveolar-capillary basement membrane causing alveolar bleeding. Inhalation of cocaine and other sympathomimetic agents are described as one of many pathologic causes. We describe what is to the author's knowledge the first reported case of DAH caused by inhalation of bupropion, a norepinephrine-dopamine reuptake inhibitor, which was successfully treated with systemic steroids. This case adds a novel agent to the known pathologic causes of DAH and introduces a novel form of bupropion toxicity, which should be considered as a cause in cases of DAH in the appropriate clinical context. The case also highlights the potential for further research into the pathologic interactions of bupropion at the alveolar basement membrane., Competing Interests: Financial/Nonfinancial Disclosures None declared, (Copyright © 2024 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)