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Background/Objectives: We assessed the effectiveness and safety of vitamin K antagonists (VKAs) versus direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) using artificial intelligence techniques. Methods: This is a retrospective study in 15 Spanish hospitals (2014–2020), including adult AF patients with no history of anticoagulation, thrombosis events, rheumatic mitral valvular heart disease, mitral valve stenosis, or pregnancy. We employed EHRead® technology based on natural language processing (NLP) and machine learning (ML), along with SNOMED-CT terminology, to extract clinical data from electronic health records (EHRs). Using propensity score matching (PSM), the effectiveness, safety, and hospital mortality of VKAs versus DOACs were analyzed through Kaplan–Meier curves and Cox regression. Results: Out of 138,773,332 EHRs from 4.6 million individuals evaluated, 44,292 patients were included, 79.6% on VKAs and 20.4% on DOACs. Most patients were elderly [VKA 78 (70, 84) and DOAC 75 (66, 83) years], with numerous comorbidities (75.5% and 70.2% hypertension, 47.2% and 39.9% diabetes, and 40.3% and 34.8% heart failure, respectively). Additionally, 60.4% of VKA and 48.7% of DOAC users had a CHA2DS2-VASc Score ≥4. After PSM, 8929 patients per subgroup were selected. DOAC users showed a lower risk of thrombotic events [HR 0.81 (95% CI 0.70–0.94)], minor bleeding [HR 0.89 (95% CI 0.83–0.96)], and mortality [HR 0.80 (95% CI 0.69–0.92)]. Conclusions: Applying NLP and ML, we generated valuable real-world evidence on anticoagulated AF patients in Spain. Even in complex populations, DOACs have demonstrated a better safety and effectiveness profile than VKAs. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases are the leading cause of death globally, making the use of oral anticoagulants for prevention increasingly important. Historically, warfarin has played a significant role in this context. In recent years, introduction of new oral anticoagulants, such as rivaroxaban, apixaban, dabigatran, and edoxaban, has been seen. This study evaluates the risk associated with the use of oral anticoagulants by analyzing spontaneous adverse drug reactions reported to the Portuguese Pharmacovigilance System from 2012 to 2021. The study includes 951 adverse drug reactions reports, with the majority (n = 770; 80.97%) classified as serious. Of the 770 serious adverse drug reactions reports, the most commonly reported seriousness criterion was "Clinically Important" (n = 350; 45.45%). In terms of demographics, there was a higher reporting rate among the elderly population, with a greater prevalence of females. The System Organ Class group with the highest number of adverse drug reactions was "Gastrointestinal disorders," with the most commonly reported Preferred Term being "Gastrointestinal hemorrhage," and dabigatran was the most frequently reported drug. In summary, oral anticoagulants have adverse drug reactions that require continuous monitoring. Accurate identification and monitorization of adverse drug reactions is an important starting point to improve drug safety in population. [ABSTRACT FROM AUTHOR]

Background: The optimal approach for anticoagulation in patients with bioprosthetic valves and atrial fibrillation (AF) remains a subject of debate. A meta-analysis using updated evidence to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) compared to vitamin K antagonists (VKAs) in patients with AF and bioprosthetic valves to address this controversy. Methods: A comprehensive search was conducted in multiple databases, including PubMed, Scopus, Web of Science, ProQuest, and the Cochrane Central Register of Controlled Trials, up until March 2023. The search aimed to identify relevant randomized controlled trials (RCTs) that examined the efficacy and safety outcomes of both direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in patients with bioprosthetic valves and atrial fibrillation. The primary outcomes of interest were major bleeding and all-cause mortality. Results: Our study demonstrated that despite the difference was not significant, the hazard of all-cause mortality was 2.5% higher in the DOAC group (HR = 1.03, 95% CI = [0.88, 1.19], p-value =.75). Similarly, the hazard of stroke (HR = 1.03, 95% CI = [0.87, 1.32], p-value =.71) and major bleeding (HR = 1.11, 95% CI = [0.89, 1.38], p-value =.36) were found to be respectively 3.2 and 10.7% higher in the DOAC group, although the difference was not significant. However, the hazard of intracranial hemorrhage was found to be 28.8 lower in the DOAC treatment group (HR = 0.71, 95% CI = [0.39, 1.31], p-value =.27), which again was not statistically significant. Conclusions: Our meta-analysis demonstrates that in patients undergoing bioprosthetic valve surgery and presenting with AF afterward, DOAC and VKA are similar regarding life-threatening and all-cause mortality outcomes, including major bleeding, stroke, and intracranial hemorrhage. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the safety and efficacy of antithrombotic strategies by age in patients with atrial fibrillation and acute coronary syndrome and/or percutaneous coronary intervention in AUGUSTUS. Patients were stratified into 3 age groups: <65, 65-74, and ≥75 years. Outcomes of interest were major or clinically relevant non-major bleeding, major bleeding, death or rehospitalization, and ischemic events. Treatment effects of apixaban vs. vitamin K antagonist (VKA) and aspirin vs. placebo were assessed across age groups using Cox models. Of 4614 patients, 1267 (27.5%) were <65, 1802 (39.0%) were 65-74, and 1545 (33.5%) were ≥75 years. Apixaban was associated with lower rates of major or clinically relevant non-major bleeding than VKA (<65: HR 0.69 [0.47-1.00]; 65-74: HR 0.57 [0.43-0.75]; ≥75: HR 0.81 [0.63-1.04]). Death or hospitalization occurred less often with apixaban, regardless of age. No differences were observed in rates of ischemic events between apixaban and VKA according to age. Aspirin was associated with higher rates of bleeding than placebo (<65: HR 1.67 [1.15-2.43]; 65-74: HR 2.32 [1.73-3.10]; ≥75: HR 1.69 [1.31-2.19]). Rates of death or rehospitalization and ischemic events were similar among patients receiving aspirin or placebo across age groups. Apixaban was associated with greater absolute reduction in bleeding than VKA in older age groups, reflecting their higher hemorrhagic risk. Aspirin increased bleeding in all age groups vs. placebo. Our findings support the use of apixaban plus a purinergic receptor P2Y 12 (P2Y 12) inhibitor without aspirin in patients with atrial fibrillation and recent acute coronary syndrome/percutaneous coronary intervention, regardless of age. [ABSTRACT FROM AUTHOR]

Introduction: We previously conducted a prospective, observational post-marketing surveillance study to assess the safety and effectiveness of four-factor prothrombin complex concentrate (4F-PCC) for rapid vitamin K antagonist (VKA) reversal in Japanese patients. Methods: This subgroup analysis compared the safety, especially thromboembolic events (TEEs), and effectiveness of 4F-PCC by stratifying patients into two subgroups according to baseline international normalized ratio (INR) levels with < 2.0 and ≥ 2.0. Results: Of 1271 eligible patients, 215 (17.9%) had INR < 2.0 and 987 (82.1%) had INR ≥ 2.0. Overall baseline characteristics were similar between groups; age (74.0 years vs 74.0 years), body mass index (22.1 kg/m2 vs 21.9 kg/m2), ratio of inpatients (90.2% vs 88.7%), manifested atrial fibrillation (46.0% vs 48.8%). Median INRs at baseline were 1.72 (minimum 0.92, maximum 1.99) in the INR < 2.0 group and 2.95 (2.00, 27.11) in the INR ≥ 2.0 group. The most common reason for 4F-PCC administration was intracranial hemorrhage (67.0% vs 59.5%), and lesser gastrointestinal bleeding (0.9% vs 7.5%). After 4F-PCC administration (average doses 24.5 IU/kg [INR < 2.0 group] and 29.2 IU/kg [INR ≥ 2.0 group]), INRs were significantly reduced to 1.21 (− 28%) and 1.31 (− 68%), respectively, and resulted in hemostasis in a similarly rapid manner. The incidences of adverse drug reactions were 3.7% in each group. TEEs occurred in 4 (1.9%) patients in the INR < 2.0 group and 11 (1.1%) patients in the INR ≥ 2.0 group and were predominantly composed of stroke, while similar rates (67.0% vs 62.9%) of bleeding events post-anticoagulant resumption were observed between groups. Conclusion: This study supports the favorable tolerability and efficacy of 4F-PCC regardless of baseline INR (< 2.0 or ≥ 2.0), with a prompt reduction of INR and substantial hemostatic effectiveness in the real-world setting for patients requiring urgent VKA reversal, although no indicated 4F-PCC dose for VKA reversal exists for INR < 2.0 to date. [ABSTRACT FROM AUTHOR]

Introduction: Patients on systemic oral anticoagulation with vitamin K antagonists (VKA) or non-vitamin K oral anticoagulants (NOAC) often require triple therapy following percutaneous coronary intervention, substantially increasing the risk of bleeding. Gastroprotective agents like proton pump inhibitors (PPI) are often employed to mitigate this risk, despite potential competitive inhibition between P2Y12-receptor inhibitors, NOACs, and VKAs. While the interactions and clinical outcomes of PPIs and DAPT have been frequently explored in literature, not many studies have evaluated the same outcomes for triple therapy. Areas covered: This comprehensive narrative review of three studies on PPIs and triple from the PubMed/MEDLINE database supplemented by 23 other relevant studies aims to use the available literature to analyze the potential interactions between PPIs and triple therapy while shedding light on their mechanisms, clinical implications, and areas for optimization. Expert opinion: If triple therapy is indicated following PCI, then patients at high-risk for bleeding may benefit from transition to apixaban and a PPI to lower the risk of gastrointestinal bleeding. More research is needed to determine the role of PPIs in triple therapies in prevention of gastrointestinal bleeding or potentiation of other adverse outcomes. [ABSTRACT FROM AUTHOR]

Managing anticoagulation therapy in individuals with atrial fibrillation who also have liver disease is highly challenging due to altered blood clotting processes and the risk of bleeding due to liver dysfunction. The literature highlights the complex nature of anticoagulant therapy in these patients, emphasizing the need for personalized treatment methods that take into account both thrombosis and bleeding risks. Research has shown a higher occurrence of atrial fibrillation in people with cirrhosis, highlighting the need to find the best anticoagulation methods based on the severity of liver disease and patient-specific factors. The debate over the safety and effectiveness of direct oral anticoagulants compared to traditional drugs like warfarin in cirrhotic patients with atrial fibrillation is still ongoing. Collaborative initiatives between experts in hepatology and cardiology are needed to address the complicated interplay between liver disease and atrial fibrillation, promoting interdisciplinary care models that enhance patient safety and treatment effectiveness. By prioritizing a patient-centered approach guided by extensive research, future directions in the hemostatic management of cirrhotic patients with atrial fibrillation may improve clinical decision-making and therapeutic outcomes.

Background: The impact of chronic oral anticoagulant (OACs) use on long‐term post‐discharge outcomes after coronavirus disease 2019 (COVID‐19) hospitalisation remains unclear. Herein, we compared clinical outcomes up to 2‐years after COVID‐19 hospitalisation between patients on vitamin K antagonists (VKAs), direct‐acting OACs (DOACs) and no OAC therapy. Methods: Data from TriNetX, a global federated health research network, were used. Adult patients on VKAs, DOACs or no OAC therapy at diagnosis of COVID‐19 between 20 January 2020 and 31 December 2021, who were hospitalised for COVID‐19, were included. The primary outcomes were all‐cause mortality, ischaemic stroke/transient ischaemic attack (TIA)/systemic embolism (SE) and the composite of intracranial haemorrhage (ICH)/gastrointestinal bleeding, at 2 years after COVID‐19 hospitalisation. Results: We included 110,834 patients with COVID‐19. Following propensity score matching (PSM), we identified a decreased mortality risk in DOAC‐treated patients compared to the no OAC cohort (RR.808, 95% CI.751–.870). A higher risk of ischaemic stroke/TIA/SE was observed in VKA users compared to DOAC users (RR 1.100, 95% CI 1.020–1.220) and in VKA users compared to patients not taking OAC (RR 1.400, 95% CI 1.140–1.720). VKA use was associated with a greater risk of ICH/gastrointestinal bleeding than DOAC users (RR 1.198, 95% CI 1.066–1.347), while DOAC users had a lower risk compared to no OAC‐treated patients (RR.840, 95% CI.754–.936). Conclusion: COVID‐19 patients taking prior DOACs were associated with lower long‐term mortality risk and ICH/gastrointestinal bleeding than patients not taking OAC. Compared to patients on DOACs, VKA users were associated with higher risks of mortality, ischaemic stroke/TIA/SE and ICH/gastrointestinal bleeding. [ABSTRACT FROM AUTHOR]

Background: As direct oral anticoagulants (DOACs) have become widely recommended as first-line anticoagulation therapy, patients who remain on warfarin are likely those unable to afford, adhere to, or utilize DOAC therapy due to the presence of a contraindication. It is currently unknown how availability of DOACs have affected populations being managed at warfarin (VKA) anticoagulation clinics. Methods: This was a retrospective chart review assessing warfarin-treated patients at an outpatient anticoagulation clinic. The primary endpoint was the 6-month time in therapeutic range (TTR) before and after DOACs were recommended as first-line therapy by clinical guidelines. Study periods were January to June 2015, before DOACs were recommended over VKA, and January to June 2022, when DOACs were often recommended over VKA. TTR, demographic changes, and the presence of contraindications to DOAC therapy in the clinic population between the two time periods were assessed. Results: No difference in 6-month TTR was observed between study periods (59% in 2015 vs 63% in 2022; P =.45). Patient demographics did not significantly vary, which may be due to the clinic retaining 45% of patients between both time periods. Contraindications to DOAC therapy were identified in 39% of the 2015 group and 49% of the 2022 group (P =.18). The most common contraindication was indication for anticoagulation. Conclusion: Availability of DOACs did not seem to significantly affect the population or management of warfarin-treated patients at an outpatient anticoagulation clinic, however, contraindications and potential challenges to use of DOAC therapy are present in many patients. [ABSTRACT FROM AUTHOR]

Background: Thromboembolic events are serious left ventricular thrombus (LVT) complications. Despite the limitations of vitamin K antagonist (VKA) drugs, it continues to be the recommended oral anticoagulation for LVT. Recently, nonvitamin K oral antagonist (NOAC) has gained popularity as an off-labeled treatment for systemic embolism prevention in LVT. Objective: In this study, we aim to compare the outcomes (stroke and bleeding) of warfarin versus NOAC therapy in patients with LVT. Methods: This retrospective cohort study compares NOAC and VKA therapy in LVT patients. We enrolled 201 patients with an echocardiography-confirmed LVT from January 2018 to December 2022. Patients who received NOAC therapy (NOAC, n = 77) were compared to VKA patients (VKA, n = 124). The primary endpoint was a composite of stroke, minor and major bleeding. Results: The median follow-up time was 17 months (25th–75th percentiles: 8–38). On unmatched analysis, both groups had no difference in major bleeding (log-rank, P = 0.61) and stroke (log-rank, P = 0.77). However, all bleeding events were higher with NOAC (log-rank, P = 0.01). On matched analysis, there was no difference between both groups in the overall bleeding events (P = 0.08), major bleeding (P = 0.57), and stroke (P = 0.66). Minor bleeding was significantly lower in the VKA group (P = 0.04). Conclusion: In patients with LVT, NOAC was as effective as VKA in stroke prevention without increasing the risk of major bleeding.

Introduction: Rheumatic heart disease with persistent atrial fibrillation (RHD‐AF) is associated with increased morbidity. However, there is no standardized approach for the maintenance of sinus rhythm (SR) in them. We aimed to determine the utility of a stepwise approach to achieve SR in RHD‐AF. Methods: Consecutive patients with RHD‐AF from July 2021 to August 2023 formed the study cohort. The stepwise approach included pharmacological rhythm control and/or electrical cardioversion (Central illustration). In patients with recurrence, additional options included AF ablation or pace and ablate strategy with conduction system pacing or biventricular pacing. Clinical improvement, NT‐proBNP, 6‐Minute Walk Test (6MWT), heart failure (HF) hospitalizations, and thromboembolic complications were documented during follow‐up. Results: Eighty‐three patients with RHD‐AF (mean age 56.13 ± 9.51 years, women 72.28%) were included. Utilizing this approach, 43 (51.81%) achieved and maintained SR during the study period of 11.04 ± 7.14 months. These patients had improved functional class, lower NT‐proBNP, better distance covered for 6MWT, and reduced HF hospitalizations. The duration of AF was shorter in patients who achieved SR, compared to those who remained in AF (3.15 ± 1.29 vs 6.93 ± 5.23, p = 0.041). Thirty‐five percent (29) maintained SR after a single cardioversion over the study period. Only one underwent AF ablation. Of the 24 who underwent pace and ablate strategy, atrial lead was implanted in 22 (hybrid approach), and 50% of these achieved and maintained SR. Among these 24, none had HF hospitalizations, but patients who maintained SR had further improvement in clinical and functional parameters. Conclusions: RHD‐AF patients who could achieve SR with a stepwise approach, had better clinical outcomes and lower HF hospitalizations. [ABSTRACT FROM AUTHOR]

Managing anticoagulation therapy in individuals with atrial fibrillation who also have liver disease is highly challenging due to altered blood clotting processes and the risk of bleeding due to liver dysfunction. The literature highlights the complex nature of anticoagulant therapy in these patients, emphasizing the need for personalized treatment methods that take into account both thrombosis and bleeding risks. Research has shown a higher occurrence of atrial fibrillation in people with cirrhosis, highlighting the need to find the best anticoagulation methods based on the severity of liver disease and patient-specific factors. The debate over the safety and effectiveness of direct oral anticoagulants compared to traditional drugs like warfarin in cirrhotic patients with atrial fibrillation is still ongoing. Collaborative initiatives between experts in hepatology and cardiology are needed to address the complicated interplay between liver disease and atrial fibrillation, promoting interdisciplinary care models that enhance patient safety and treatment effectiveness. By prioritizing a patient-centered approach guided by extensive research, future directions in the hemostatic management of cirrhotic patients with atrial fibrillation may improve clinical decision-making and therapeutic outcomes. [ABSTRACT FROM AUTHOR]

Background: Thromboembolic events are serious left ventricular thrombus (LVT) complications. Despite the limitations of vitamin K antagonist(VKA) drugs, it continues to be the recommended oral anticoagulation for LVT. Recently, nonvitamin K oral antagonist(NOAC) has gained popularity as an off‑labeled treatment for systemic embolism prevention in LVT. Objective: In this study, we aim to compare the outcomes (stroke and bleeding) of warfarin versus NOAC therapy in patients with LVT. Methods: This retrospective cohort study compares NOAC and VKA therapy in LVT patients. We enrolled 201 patients with an echocardiography‑confirmed LVT from January 2018 to December 2022. Patients who received NOAC therapy (NOAC, n = 77) were compared to VKA patients (VKA, n = 124). The primary endpoint was a composite of stroke, minor and major bleeding. Results: The median follow‑up time was 17 months (25th–75th percentiles: 8–38). On unmatched analysis, both groups had no difference in major bleeding (log‑rank, P = 0.61) and stroke (log‑rank, P = 0.77). However, all bleeding events were higher with NOAC (log‑rank, P = 0.01). On matched analysis, there was no difference between both groups in the overall bleeding events (P = 0.08), major bleeding (P = 0.57), and stroke (P = 0.66). Minor bleeding was significantly lower in the VKA group (P = 0.04). Conclusion: In patients with LVT, NOAC was as effective as VKA in stroke prevention without increasing the risk of major bleeding. [ABSTRACT FROM AUTHOR]

Non-activated four-factor prothrombin complex concentrate (4 F-PCC) has emerged as the preferred reversal strategy for patients on warfarin with life-threatening bleeding. Current dosing recommendations for 4 F-PCC require pre-treatment international normalized ratio (INR) and bodyweight values, resulting in ordering and administration delays. Studies have shown that alternative dosing regimens are safe and efficacious. This retrospective, single-center, pre- and post-protocol analysis was conducted to assess the efficacy of a pharmacist driven modified fixed-dose 4 F-PCC regimen versus package insert weight- and INR-based dosing regimen for warfarin reversal. The primary outcome was achievement of INR less than two. Secondary outcomes included dose and cost of 4 F-PCC, a time analysis, incidence of concomitant vitamin K administration, and incidence of thrombosis within seven days of 4 F-PCC. There were 195 patients included in the analysis, with 74 in the pre-cohort and 121 in the post-cohort. Baseline characteristics were similar between cohorts with the most common indication for warfarin use being atrial fibrillation (48.6% versus 47.1%) and reversal being intracerebral hemorrhage (68.9% versus 43.0%). Achievement of the primary endpoint occurred in 92% versus 95% (p = 0.097) of patients. A statistically significant difference was seen between cohorts regarding median dose and cost of 4 F-PCC administered (p < 0.001). Eleven thromboembolic events occurred with three events in the pre-cohort and eight events in the post-cohort (p = 0.453). A fixed-dose of 1500IU of 4 F-PCC was effective in reversing INR to less than two in most patients regardless of reversal indication with minimal thrombotic risks. Highlights: No consensus exists for the ideal dosing scheme for 4 F-PCC for warfarin reversal. We describe our experience with a pharmacist driven modified-fixed dose 4 F-PCC protocol for warfarin reversal. No difference in reversal of INR < 2 was seen between package-insert weight and INR based dosing compared to modified fixed-dose 4 F-PCC dosing for warfarin reversal. Future research regarding to establish non-inferiority between fixed-dose and package-insert dosing is warranted. [ABSTRACT FROM AUTHOR]

Abstract Cardiovascular diseases are the leading cause of death globally, making the use of oral anticoagulants for prevention increasingly important. Historically, warfarin has played a significant role in this context. In recent years, introduction of new oral anticoagulants, such as rivaroxaban, apixaban, dabigatran, and edoxaban, has been seen. This study evaluates the risk associated with the use of oral anticoagulants by analyzing spontaneous adverse drug reactions reported to the Portuguese Pharmacovigilance System from 2012 to 2021. The study includes 951 adverse drug reactions reports, with the majority (n = 770; 80.97%) classified as serious. Of the 770 serious adverse drug reactions reports, the most commonly reported seriousness criterion was “Clinically Important” (n = 350; 45.45%). In terms of demographics, there was a higher reporting rate among the elderly population, with a greater prevalence of females. The System Organ Class group with the highest number of adverse drug reactions was “Gastrointestinal disorders,” with the most commonly reported Preferred Term being “Gastrointestinal hemorrhage,” and dabigatran was the most frequently reported drug. In summary, oral anticoagulants have adverse drug reactions that require continuous monitoring. Accurate identification and monitorization of adverse drug reactions is an important starting point to improve drug safety in population.

The document titled "Corrigendum: Direct oral anticoagulants for the treatment of cerebral venous thrombosis – a protocol of an international phase IV study" in the journal Frontiers in Neurology outlines corrections made to the Statistical Analysis Plan. Changes include the addition of country income group as a confounder and the use of last observation carried forward approach for missing data. The study will analyze primary and secondary outcomes using propensity score inverse probability treatment weighting and sensitivity analyses. The authors emphasize that these corrections do not alter the scientific conclusions of the original article. [Extracted from the article]

Shouki Bazarbashi,1 Heba Mohamed El Zawahry,2 Tarek Owaidah,3 Mohammad A AlBader,4 Ashraf Warsi,5– 7 Mahmoud Marashi,8,9 Emad Dawoud,10 Hassan Jaafar,11 Sherif M Sholkamy,12 Fady Haddad,13 Alexander T Cohen14 1Section of Medical Oncology, Oncology Center, King Faisal Specialist Hospital and Research Center, Alfaisal University, Riyadh, Saudi Arabia; 2Department of Medical Oncology, The National Cancer Institute, Cairo University, Cairo, Egypt; 3Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center, Alfaisal University, Riyadh, Saudi Arabia; 4Hematology Unit, Al Sabah Hospital, South Surra, Kuwait; 5Department of Adult Hematology, Princess Noorah Oncology Center, King Abdulaziz Medical City, Ministry of National Guard Health Affairs–Western Region, Jeddah, Saudi Arabia; 6College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs–Western Region, Jeddah, Saudi Arabia; 7King Abdullah International Medical Research Center, Ministry of National Guard Health Affairs-Western Region, Jeddah, Saudi Arabia; 8Hematology Department, Dubai Hospital, Dubai, United Arab Emirates; 9Department of Hematology, Mediclinic City Hospital, Dubai, United Arab Emirates; 10Department of Oncology, Tawam Hospital, Al Ain, United Arab Emirates; 11Department of Oncology, Sheikh Khalifa Specialty Hospital, Ras Al-Khaimah, United Arab Emirates; 12Department of Vascular Surgery, Ain Shams University, Cairo, Egypt; 13Vascular and Endovascular Surgery, American University of Beirut Medical Center, Beirut, Lebanon; 14Department of Haematological Medicine, Guy’s and St Thomas’ Hospitals NHS Foundation Trust, King’s College London, London, UKCorrespondence: Shouki Bazarbashi, Section of Medical Oncology, Oncology Center, King Faisal Specialist Hospital and Research Center, Alfaisal University, 1 Alzahrawi Street, Riyadh, 11211, Saudi Arabia, Tel +966 505443546, Email bazarbashi@gmail.comAbstract: Venous thromboembolism is a leading cause of morbidity and mortality in patients with active cancer who require anticoagulation treatment. Choice of anticoagulant is based on careful balancing of the risks and benefits of available classes of treatment: vitamin K antagonists, low-molecular-weight heparin (LMWH), and direct oral anticoagulants (DOACs). Results from randomized controlled trials have shown the consistent efficacy of DOACs versus LMWH in the treatment of cancer-associated venous thromboembolism (VTE). However, increased major gastrointestinal bleeding was observed for edoxaban and rivaroxaban, but not apixaban, compared with LMWH dalteparin. Most guidelines recommend DOACs for the treatment of cancer-associated VTE in patients without gastrointestinal or genitourinary cancer, and with considerations for renal impairment and drug–drug interactions. These updates represent a major paradigm shift for clinicians in the Middle East and North Africa. The decision to prescribe a DOAC for a patient with cancer is not always straightforward, particularly in challenging subgroups of patients with an increased risk of bleeding. In patients with gastrointestinal malignancies who are at high risk of major gastrointestinal bleeds, apixaban may be the preferred DOAC; however, caution should be exercised if patients have upper or unresected lower gastrointestinal tumors. In patients with gastrointestinal malignancies and upper or unresected lower gastrointestinal tumors, LMWH may be preferred. Vitamin K antagonists should be used only when DOACs and LMWH are unavailable or unsuitable. In this review, we discuss the overall evidence for DOACs in the treatment of cancer-associated VTE and provide treatment suggestions for challenging subgroups of patients with cancer associated VTE.Plain Language Summary: Patients with cancer are at risk of blood clots forming in their veins, which can cause illness and death. To prevent such blood clots, most patients with cancer need anticoagulant therapy. There are three types of anticoagulants available for the treatment of cancer-associated blood clots in a vein, namely, vitamin K antagonists, low-molecular-weight heparin (LMWH), and direct oral anticoagulants (DOACs). Drug trials have shown that DOACs are more effective than LMWH; however, DOACs can have a greater risk of causing major gastrointestinal bleeding. Among DOACs, edoxaban and rivaroxaban are drugs associated with higher rates of gastrointestinal bleeding. Recently updated guidelines for doctors recommend that DOACs be used as the first treatment for patients with cancer at risk of blood clot formation in a vein. For doctors in the Middle East and North Africa, this new approach differs from existing practices. Notably, choosing a treatment also depends on the type of cancer, because gastrointestinal cancers and cancers of the genitals and urinary system have an especially high risk of gastrointestinal bleeding. The choice also depends on the presence of kidney problems, drug–drug interactions, and access to the drugs. Apixaban may be the preferred DOAC in patients with gastrointestinal cancer, but this drug should be used with care in patients with upper or unresected lower gastrointestinal tumors. For patients with upper or unresected lower gastrointestinal tumors, treatment with LMWH may be preferred. Vitamin K antagonists should be used only when DOACs and LMWH are unavailable or unsuitable.Keywords: anticoagulation, apixaban, cancer, vitamin K antagonist, low-molecular-weight heparin

[Display omitted] • About 10% of patients with ACS are treated by VKAs or NOACs. • The initial management of these patients is highly complex. • New guidelines specify that, only during PCI, a bolus of UFH is recommended if: ∘ the patient is receiving a NOAC, or, ∘ the INR is < 2.5 in a patient being treated with a VKA. • No randomized study has been performed in this specific population. • Proposed algorithms are therefore a synthesis of diagnostic/therapeutic approaches. Around 10% of patients with acute coronary syndrome are treated by vitamin K antagonists or non-vitamin K antagonist oral anticoagulants for various indications. The initial management of these patients is highly complex, and new guidelines specify that, only during percutaneous coronary intervention, a bolus of unfractionated heparin is recommended in one of the following circumstances: (1) if the patient is receiving a non-vitamin K antagonist oral anticoagulant; or (2) if the international normalized ratio is < 2.5 in a patient being treated with a vitamin K antagonist. In this review, we report on five key messages essential for the management of these patients. There are no randomized studies to date, and we propose two diagnostic and/or therapeutic decision algorithms. However, randomized studies are needed to validate these strategies. [ABSTRACT FROM AUTHOR]

Background: Toxicity or treatment failure related to drug-drug interactions (DDIs) are known to significantly affect morbidity and hospitalization rates. Despite the availability of numerous databases for DDIs identification and management, their information often differs. Oral anticoagulants are deemed at risk of DDIs and a leading cause of adverse drug events, most of which being preventable. Although many databases include DDIs involving anticoagulants, none are specialized in them. Aim and method: This study aims to compare the DDIs information content of four direct oral anticoagulants and two vitamin K antagonists in three major DDI databases used in Switzerland: Lexi-Interact, Pharmavista, and MediQ. It evaluates the consistency of DDIs information in terms of differences in severity rating systems, mechanism of interaction, extraction and documentation processes and transparency. Results: This study revealed 2'496 DDIs for the six anticoagulants, with discrepant risk classifications. Only 13.2% of DDIs were common to all three databases. Overall concordance in risk classification (high, moderate, and low risk) was slight (Fleiss' kappa = 0.131), while high-risk DDIs demonstrated a fair agreement (Fleiss' kappa = 0.398). The nature and the mechanism of the DDIs were more consistent across databases. Qualitative assessments highlighted differences in the documentation process and transparency, and similarities for availability of risk classification and references. Discussion: This study highlights the discrepancies between three commonly used DDI databases and the inconsistency in how terminology is standardised and incorporated when classifying these DDIs. It also highlights the need for the creation of specialised tools for anticoagulant-related interactions. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate the risks and outcomes of patients with long-term oral anticoagulation (OAC) undergoing spine surgery. Methods: All patients on long-term OAC who underwent spine surgery between 01/2005 and 06/2015 were included. Data were prospectively collected within our in-house Spine Surgery registry and retrospectively supplemented with patient chart and administrative database information. A 1:1 propensity score-matched group of patients without OAC from the same time interval served as control. Primary outcomes were post-operative bleeding, wound complications and thromboembolic events up to 90 days post-surgery. Secondary outcomes included intraoperative blood loss, length of hospital stay, death and 3-month post-operative patient-rated outcomes. Results: In comparison with the control group, patients with OAC (n = 332) had a 3.4-fold (95%CI 1.3–9.0) higher risk for post-operative bleeding, whereas the risks for wound complications and thromboembolic events were comparable between groups. The higher bleeding risk was driven by a higher rate of extraspinal haematomas (3.3% vs. 0.6%; p = 0.001), while there was no difference in epidural haematomas and haematoma evacuations. Risk factors for adverse events among patients with OAC were mechanical heart valves, posterior neck surgery, blood loss > 1000 mL, age, female sex, BMI > 30 kg/m2 and post-operative PTT levels. At 3-month follow-up, most patients reported favourable outcomes with no difference between groups. Conclusion: Although OAC patients have a higher risk for complications after spine surgery, the risk for major events is low and patients benefit similarly from surgery. [ABSTRACT FROM AUTHOR]

Venous thromboembolism (VTE) is a rare and heterozygous disease in children. Management of VTE in children is complicated by age-related differences in epidemiology, recurrent VTE and bleeding risk, hemostatic proteins and pharmacokinetics of anticoagulants. Recently, the choice of anticoagulation has expanded to oral factor IIa and Xa inhibitors, which have been authorized for children for treatment of acute VTE and extended secondary prevention. These drugs have several properties that make them extremely suitable for use in children, including oral administration, antithrombin independence, less interactions with food and drugs and no need for monitoring. Unfortunately, the phase 3 studies had many exclusion criteria, and only a few term neonates and infants were included in these studies. Additional real-world data is needed to make evidence-based recommendations in these age and patient groups, as well. • Anticoagulation management of pediatric venous thromboembolism is challenging. • Dabigatran and rivaroxaban are changing the therapeutic landscape. • Unfortunately, their phase 3 studies had many exclusion criteria. • Additional real-world data is needed in specific age and patient groups. [ABSTRACT FROM AUTHOR]

Introduction: Limited data are available regarding the safety and effectiveness of 4-factor prothrombin complex concentrate (4F-PCC) in patients experiencing major hemorrhage or requiring expeditious surgical intervention, both globally and within Japan. Methods: We executed a prospective, observational post-marketing surveillance study of patients receiving 4F-PCC for the first time between September 19, 2017 and August 15, 2018 in Japan. Patients were subjected to a comprehensive follow-up for a duration of 4 weeks. Results: Of 1381 eligible patients, 1271 (92%) received a vitamin K antagonist. Among these, 58% were aged ≥ 75 years, 49% manifested atrial fibrillation, 17% presented with valvular heart disease, and 6% exhibited venous thromboembolism. The median (range) international normalized ratio was 2.67 (0.96–27.11) at baseline and 1.21 (0.45–6.61) at first measurement post-administration of 4F-PCC. The most common reason for 4F-PCC administration was intracranial hemorrhage (59.6%), followed by gastrointestinal bleeding (6.6%). Hemostatic effectiveness was achieved in 85.8% of patients. The incidences of adverse drug reactions (ADRs) and serious ADRs were 3.9% and 2.8%, respectively. Thromboembolic events (TEEs) occurred in 20 (1.5%) patients, with a mean onset of 10 days. The majority of TEEs were classified as nervous system disorders (55%). At the time of TEE, only 13% of patients resumed anticoagulant therapy. Conclusion: The incidence of TEEs following treatment with 4F-PCC did not surpass those observed in phase 3 trials. No novel safety signals were identified. The safety and effectiveness of 4F-PCC in Japanese real-world practice were in harmony with the observations of prior studies. [ABSTRACT FROM AUTHOR]

Abstract Introduction Limited data are available regarding the safety and effectiveness of 4-factor prothrombin complex concentrate (4F-PCC) in patients experiencing major hemorrhage or requiring expeditious surgical intervention, both globally and within Japan. Methods We executed a prospective, observational post-marketing surveillance study of patients receiving 4F-PCC for the first time between September 19, 2017 and August 15, 2018 in Japan. Patients were subjected to a comprehensive follow-up for a duration of 4 weeks. Results Of 1381 eligible patients, 1271 (92%) received a vitamin K antagonist. Among these, 58% were aged ≥ 75 years, 49% manifested atrial fibrillation, 17% presented with valvular heart disease, and 6% exhibited venous thromboembolism. The median (range) international normalized ratio was 2.67 (0.96–27.11) at baseline and 1.21 (0.45–6.61) at first measurement post-administration of 4F-PCC. The most common reason for 4F-PCC administration was intracranial hemorrhage (59.6%), followed by gastrointestinal bleeding (6.6%). Hemostatic effectiveness was achieved in 85.8% of patients. The incidences of adverse drug reactions (ADRs) and serious ADRs were 3.9% and 2.8%, respectively. Thromboembolic events (TEEs) occurred in 20 (1.5%) patients, with a mean onset of 10 days. The majority of TEEs were classified as nervous system disorders (55%). At the time of TEE, only 13% of patients resumed anticoagulant therapy. Conclusion The incidence of TEEs following treatment with 4F-PCC did not surpass those observed in phase 3 trials. No novel safety signals were identified. The safety and effectiveness of 4F-PCC in Japanese real-world practice were in harmony with the observations of prior studies.

Studies comparing long-term outcomes between non–vitamin K antagonist (VKA) oral anticoagulant agents (direct oral anticoagulant agents [DOACs]) and VKA anticoagulant agents after transcatheter aortic valve replacement (TAVR) are scarce, with conflicting results. The aim of this study was to examine the periprocedural, short-term, and long-term safety and effectiveness of DOACs vs VKAs in patients undergoing TAVR via femoral access with concomitant indications for oral anticoagulation. Consecutive patients undergoing transfemoral TAVR in the prospective national SwissTAVI Registry between February 2011 and June 2021 were analyzed. Net clinical benefit (a composite of all-cause mortality, myocardial infarction, stroke, and life-threatening or major bleeding) and the primary safety endpoint (a composite of life-threatening and major bleeding) were compared between the VKA and DOAC groups at 30 days, 1 year, and 5 years after TAVR. After 1:1 propensity score matching, 1,454 patients were available for analysis in each group. There was no significant difference in the rate of the net clinical benefit and the safety endpoints between the groups as assessed at 30 days and 1 and 5 years post-TAVR between VKAs and DOACs. VKAs were associated with significantly higher rates of 1- year (HR: 1.28; 95% CI: 1.01-1.62) and 5-year (HR: 1.25; 95% CI: 1.11-1.40) all-cause mortality. Long-term risk for disabling stroke was significantly lower in the VKA group after excluding periprocedural events (HR: 0.64; 95% CI: 0.46-0.90). At 5 years after TAVR, VKAs are associated with a higher risk for all-cause mortality, a lower risk for disabling stroke, and a similar rate of life-threatening or major bleeding compared with DOACs. (SwissTAVI Registry; NCT01368250) [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction: Existing randomised controlled trials assessing the safety and efficacy of left atrial appendage occlusion (LAAO) in atrial fibrillation (AF) were of relatively small sample size or included patients who could receive oral anticoagulant treatment after device implantation. We compared the outcomes of patients with newly diagnosed AF who received percutaneous LAAO or direct oral anticoagulant (DOAC) treatment, in a large population from a global federated health network (TriNetX). Methods: Patients with AF treated with percutaneous LAAO were matched with those treated with DOAC between December 1, 2010, and October 1, 2018. Outcomes were all-cause mortality, ischaemic stroke, and intracranial haemorrhage (ICH) at 5 years. Results: We included 200 patients with AF, who received either LAAO or DOAC. The risk of all-cause mortality, ischaemic stroke, and ICH at 5 years was not significantly different between the two groups (risk ratio [RR] for all-cause mortality: 1.52, 95% confidence interval (CI): 0.97–2.38, RR for ischaemic stroke: 1.09, 95% CI: 0.51–2.36, and RR for ICH: 1.0, 95% CI: 0.44–2.30). Conclusion: Patients newly diagnosed with AF, eligible for DOAC, showed similar 5-year risk of death, ischaemic stroke, and ICH when comparing those who underwent percutaneous LAAO to those receiving DOAC. Future randomised controlled trials are needed to confirm the findings and advise changes in guidelines. [ABSTRACT FROM AUTHOR]

There is currently no established recommendation for antithrombotic treatment following transcatheter mitral valve replacement (TMVR). However, based on the analogy with surgical mitral bioprosthesis, vitamin K antagonists (VKAs) are predominantly used. The purpose of this study was to compare bleeding and thrombotic events associated with direct oral anticoagulants (DOACs) or VKAs in a prospective cohort of TMVR patients. We enrolled consecutive patients who underwent transseptal TMVR using a SAPIEN family prosthesis at our center between 2011 and 2023. The primary outcome was the occurrence of bleeding. VKAs were administered to patients until October 2019, after which DOACs were prescribed. The median follow-up was 4.7 months (Q1-Q3: 2.6-6.7 months). A total of 156 patients were included. The mean age was 65 ± 18.5 years, and 103 patients (66%) were women. The median EuroSCORE II was 7.48% (Q1-Q3: 3.80%-12.97%). Of the participants, 20.5% received DOACs and 79.5% were treated with VKAs. The primary outcome was observed in 50 (40%) patients in the VKA group and 3 (9%) patients in the DOAC group (adjusted HR: 0.21; 95% CI: 0.06-0.74; P = 0.02). Treatment with DOAC was associated with a shorter length of hospital stay. No significant differences were found in terms of thrombotic events, major vascular complications, stroke, or death. The use of DOACs after TMVR, compared with VKAs, appears to reduce the risk of bleeding complications and decrease the length of hospital stay for patients, without a significant increase in the risk of thrombotic events. [Display omitted] [ABSTRACT FROM AUTHOR]

• During the first 14 days of Direct oral anticoagulant (DOAC) therapy, a slight increase in serum levels of tacrolimus and cyclosporine can be found; • Serum Levels and concentration/dose ratio of Tacrolimus and cyclosporin were stable at 18 months follow-up in patients treated with DOAC; • DOACS have a similar safety and efficacy profile when compared to antagonist of vitamin K and no difference in terms of bleeding, thromboembolic events and renal function decline was found. direct oral anticoagulants (DOACs) are an alternative to conventional antagonist of vitamin-K (AVK). However, immune suppressive drugs (ISDs) may interfere with DOACs pharmacokinetic. evaluate safety and efficacy profile of DOACs compared to AVK in kidney transplant recipients (KTRs) treated with ISDs. a multi-center study from 4 Italian University hospitals enrolling consecutive KTRs on DOACs or AVK was carried out. Sixty-six patients on DOACs were compared with fifty patients on AVK with similar clinical features. Serial evaluation of renal function and serum levels of ISDs during 18 months follow-up (FU) was performed. Mean age of DOACs patients was 67±9 and mean eGFR was 58,3± 30,4mL/min/1.73m2. ISDs included tacrolimus (n=47, 71%), cyclosporin (n=13, 20%), everolimus (n=10, 7%) and sirolimus (n=4, 6%). After 14 days of DOACs therapy initiation there was a slight increase of serum levels of tacrolimus (+0.19±0.67 p=0.80) and cyclosporine (+0.12±0.25 p=0.94) not statistically significant. Levels of Tacrolimus and cyclosporin were stable at serial evaluation during 18-months follow-up. There were no thromboembolic events among patients treated with DOACs or AVK and no differences in term of major bleeding (6% vs 4% p=0.69), at long-term follow-up. There was no difference in term of eGFR decline from start therapy to 18 months FU between DOACs vs AVK therapy (-3.9±1 vs -3.8±2 p=0.82). DOACs have similar safety and efficacy than AVK among KTRs treated with ISDs. However, careful evaluation of potential drug interaction and ISDs serum levels is needed. [Display omitted] [ABSTRACT FROM AUTHOR]

A case report of a 32-year-old female patient without any traditional risk factors presented with angina to our hospital within 6 h. Her electrocardiogram (ECG) showed extensive anterior wall -ST elevation myocardial infarction (MI). She was treated with thrombolytic therapy in the form of tenecteplase and was given standard treatment for acute coronary syndrome (ACS). Her history revealed three recurrent pregnancy losses and a history of preeclampsia. Echocardiography showed regional wall motion abnormalities of the mid, distal, apex, and anterior wall with severe left ventricular systolic dysfunction. Routine blood investigations showed elevated total leukocyte count with neutrophilic predominance. With a history of recurrent pregnancy loss, she was investigated for anti-phospholipid anti-phospholipid antibody syndrome (APS) and was found to have positive lupus anticoagulant 1. She underwent coronary angiography (CAG) which showed a left main shaft 40% stenosis with an ulcerative lesion containing thrombus in the ostioproximal to mid-left anterior descending artery (LAD), other coronary arteries were normal. She was managed conservatively with glycoprotein IIb/IIIa inhibitor (Tirofiban) and switched to oral anticoagulation with Vitamin K antagonist (VKA-Acenocoumarin) along with dual-antiplatelet therapy. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of direct oral anticoagulants (DOACs) compared to warfarin in patients with inferior vena cava (IVC) thrombus. Methods: This was a single‐system, retrospective cohort study of hospitalized adult patients with IVC thrombus treated with a DOAC or warfarin therapy. The primary efficacy endpoint was the thrombus resolution on imaging, and the primary safety endpoint was major bleeding, both assessed within 6 months of hospital discharge. Secondary endpoints included hospitalization for a bleeding‐related event, pulmonary embolism, or death within 6 months of hospital discharge. Results: A total of 33 patients were included in the study. Twenty‐three (70%) patients received a DOAC, and 10 (30%) received warfarin. Of the 10 patients with repeat imaging available, complete resolution was noted in two (33%) DOAC patients and no warfarin patients (p =.5). Major bleeding occurred in two (8.7%) DOAC patients and one (10%) warfarin patient (p =.9). No significant differences in secondary endpoints were observed between groups. Conclusions: There were no differences in efficacy and safety between patients receiving DOACs or warfarin for the treatment of IVC thrombus, although results are limited by the small patient population and number of patients with repeat imaging available. [ABSTRACT FROM AUTHOR]

Background: Warfarin has been extensively used for a long time under various conditions. However, comprehensive evidence is scarce regarding the effectiveness and safety of warfarin in each group of chronic kidney disease (CKD) among Thai patients. Objective: The present study used real-world data from Thailand to determine the incidence of thromboembolism and bleeding among patients with CKD with different estimated glomerular filtration rates (eGFRs). Materials and Methods: A retrospective cohort study was conducted among Thai patients with CKD who used warfarin at three tertiary-care hospitals between January 2015 and December 2019. Patients were included and divided into five groups according to their eGFRs as N1 to N5 with eGFR greater than 60, 30 to 59, 15 to 29, less than 15 and not receiving dialysis, and less than 15 mL/minute/1.73 m² with dialysis, respectively. The incidence density was analyzed to report thromboembolism and bleeding outcomes. Results: During the follow-up period, 2.28 per 100 person-years of patients developed thromboembolism with N1 to N5 at 2.00, 2.27, 3.68, 4.66, and 1.70 per 100 person-years, respectively. Furthermore, 2.33 per 100 person-years of patients developed major bleeding with N1 to N5 at 1.17, 2.25, 4.03, 11.37, and 5.12 per 100 person-years, respectively. Conclusion: The present study found that the incidence of thromboembolism and major bleeding among patients with CKD increased across different eGFR groups who used warfarin. Interestingly, patients with CKD in the N4 group had a higher incidence of thromboembolism and major bleeding than the other groups. Thus, close monitoring and frequent follow-up are recommended for this group. [ABSTRACT FROM AUTHOR]

Background For the majority of patients with atrial fibrillation (AF), disease management has improved in recent years. However, there are still populations underrepresented or excluded in current registries and randomized controlled trials. HERA‐FIB (Heidelberg Registry of Atrial Fibrillation) was planned to assess real‐world evidence for the prevalence, demographic characteristics and management of patients with the diagnosis of AF presenting consecutively to a chest pain unit. Methods and Results HERA‐FIB is a retrospective, observational, single‐center study on patients with a diagnosis of AF presenting to a chest pain unit from June 2009 until March 2020. This article describes the structure, governance, outcome assessment, quality and data collection processes of the registry. Additionally, characteristics of populations of special interest are described. The study consecutively enrolled 10 222 patients presenting with AF to the chest pain unit of the University Hospital of Heidelberg. Clinical parameters and patient characteristics were assessed retrospectively. Outcome parameters included rates for all‐cause death, stroke, myocardial infarction and major bleedings. We were able to investigate patient cohorts of special interest such as advanced chronic kidney disease, octogenarians, and those with acute coronary syndrome who are often underrepresented in current studies and randomized controlled trials. Conclusions HERA‐FIB is one of the largest real‐world single‐center retrospective registries on patients with AF, which captures the era of transition from vitamin K antagonists to non–vitamin K oral anticoagulation regimens in clinical practice and offers the possibility to investigate patient populations usually underrepresented or excluded in current available randomized controlled trials and registries. Registration URL: https://www.clinicaltrials.gov; unique identifier: NCT05995561.

Aim. To compare the effectiveness and safety of direct oral anticoagulants (DOACs) with a vitamin K antagonist (VKA) in patients with atrial fibrillation (AF) and stage 4 and 5 chronic kidney disease (CKD).Material and methods. We searched in the PubMed, Google Scholar, and Web of Science databases from 1990 to 2022 for studies that compared DOACs with VKAs in patients with AF and stage 4 and 5 CKD. The patient, intervention, comparison, outcome (PICO) search strategy was used. Data were extracted by independent researchers and meta-analyzed.Results. A total of 6 studies were included in this meta-analysis. In terms of effectiveness, DOACs were comparable to VKAs. In terms of safety, DOACs and VKAs also had no statistical differences in hemorrhagic stroke, minor/gastrointestinal bleeding, overall mortality, but there was statistical significance in major bleeding. Conclusion. In terms of efficacy and safety, in general, DOACs were comparable to VKAs, but there were a number of following differences: the administration of DOACs to patients with stage 4 and 5 CKD, as well as those on hemodialysis, was accompanied by a significant reduction in the number of major bleedings, compared with warfarin therapy.

OBJECTIVES To compare the effectiveness of rivaroxaban and vitamin K antagonists in patients with lower limbs deep vein thrombosis. METHODOLOGY This quasi-experimental study was conducted in the Department of General Medicine in Khyber Teaching Hospital, Peshawar for six months with a sample size of sixty. Thirty patients were given Rivaroxaban (Group A) and the other thirty patients were given Vitamin K antagonist (Group B). In the Rivaroxaban group, patients had received 15mg twice daily for the first 3 weeks, 20 mg once daily from 3 weeks to 3 months, and followed by 10 mg once daily. In the Vitamin K antagonist group, patients had received a dose of warfarin of 2.5-5mg once daily, with a goal INR between 2-3. Patients were followed up for 3 months, every month and the effectiveness of both drugs was recorded. RESULTS Our study shows that in group A (Rivaroxaban), the mean age was 34 years with SD ± 10.77 and in group B (Vitamin K antagonist), the mean age was 36 years with SD ± 11.09. In Group A, 12(40%) patients were males and 18(60%) were females. In Group B, 11(37%) patients were males and 19(63%) were females. Moreover, group A was effective in 27(90%) patients while group B was effective in 25(83%). CONCLUSION Rivaroxaban is more effective than vitamin K antagonist in the treatment of lower limbs deep vein thrombosis.

Background: Both valvular heart disease (VHD) and atrial fibrillation (AF) frequently coexist. AF is an important cause of arrhythmias with a definitive cardiovascular morbidity. The use of either vitamin K antagonists (VKAs/warfarin) or direct oral anticoagulants (DOACs) (also known as new oral anticoagulants (NOACs)) has been the mainstay for preventing stroke and systemic embolism in patients with VHD and/or AF, and this has been broadly discussed. However, there are limited studies on anticoagulation therapy for patients with valvular atrial fibrillation (VAF). The main aim of this meta-analysis was to evaluate the outcomes (stroke–vascular events and intracranial bleeding) following DOAC and VKA treatment amongst patients with VAF. Methods: We identified clinical trials and observational studies published in the last 10 years. A systematic review and a meta-analysis were performed to evaluate the outcomes of patients with valvular atrial fibrillation following DOAC vs. VKA treatment. Data evaluation was performed using Review Manager 5.4; the endpoints were stroke–vascular events and intracranial bleeding following DOAC and VKA treatment amongst VAF patients. Risk ratios (RR) were evaluated with 95% confidence intervals. Using random effects models, forest plots were obtained. Heterogeneity was assessed by using the I2 statistic. Results: Eight studies were included in this metanalysis, and a total of fifteen thousand two hundred and fifteen patients (DOAC (8732) and VKA (6483)) were pooled. We found a significant risk reduction in stroke–vascular events when using DOACs in comparison with using VKAs (pooled RR: 0.76; 95% CI: 0.64–0.90, p = 0.002). A total of 14862 patients (DOAC (8561) and VKA (6301)) were pooled from a total of six studies for intracranial bleeding. We found a significant risk reduction in terms of intracranial bleeding when using DOACs in comparison with using VKAs (pooled RR: 0.43; 95% CI: 0.24–0.77, p ≤ 0.05). Conclusions: When compared to VKAs, DOAC agents were found to have less risk of stroke–vascular events and intracranial bleeding. Further prospective studies are essential to establish the efficacy and safety of DOAC agents in patients with various subtypes of VAF.

Background and Aims: Current clinical guidelines for treating left ventricular thrombus (LVT) are limited by inadequate evidence to inform the comparative efficacy of oral anticoagulants. In this meta‐analysis, we aimed to compare the efficacy and safety of direct oral anticoagulants (DOAC) to vitamin K antagonists (VKA) in patients with LVT. Methods: Four standard databases were searched for relevant literature comparing the efficacy and safety between DOAC and VKA for LVT treatment, published before August 19, 2023. Both the randomized controlled trials and observational studies were included in the analysis. The outcomes of interest were the resolution of LVT, all‐cause mortality, stroke, systemic embolism, and bleeding. Data from the selected studies were extracted and analyzed using RevMan 5.4 using odds ratio. Results: Among 3959 studies from the database search and bibliography review, 33 were included in the analysis. LVT resolution was observed in 72.59% in the DOAC group versus 67.49% in the VKA group (odds ratio [OR]: 1.28, confidence interval [CI]: 1.07–1.53). Mortality was lower in the DOAC group (11.71% vs. 18.56%) (OR: 0.60, CI: 0.36–1.00; borderline statistical significance). Likewise, bleeding events (9.60% vs. 13.19%) (OR: 0.65, CI: 0.52–0.81) and stroke (7.54% vs. 11.04%) (OR: 0.71, CI: 0.53–0.96) were also significantly lower in the DOAC group. Conclusion: DOAC use for LVT showed better thrombus resolution and reduced risk of bleeding and stroke compared to VKA. Likewise, DOAC use was associated with lower mortality with borderline statistical significance. [ABSTRACT FROM AUTHOR]

Introduction: Current guidelines recommend that patients with cerebral venous thrombosis (CVT) should be treated with vitamin K antagonists (VKAs) for 3-12 months. Direct oral anticoagulants (DOACs), however, are increasingly used in clinical practice. An exploratory randomized controlled trial including 120 patients with CVT suggested that the efficacy and safety profile of dabigatran (a DOAC) is similar to VKAs for the treatment of CVT, but large-scale prospective studies from a real-world setting are lacking. Methods: DOAC-CVT is an international, prospective, observational cohort study comparing DOACs to VKAs for the prevention of recurrent venous thrombotic events after acute CVT. Patients are eligible if they are 18 years or older, have a radiologically confirmed CVT, and have started oral anticoagulant treatment (DOAC or VKA) within 30 days of CVT diagnosis. Patients with an absolute contra-indication for DOACs, such as pregnancy or severe renal insufficiency, are excluded from the study. We aim to recruit at least 500 patients within a three-year recruitment period. The primary endpoint is a composite of recurrent venous thrombosis and major bleeding at 6 months of follow-up. We will calculate an adjusted odds ratio for the primary endpoint using propensity score inverse probability treatment weighting. Discussion: DOAC-CVT will provide real-world data on the comparative efficacy and safety of DOACs versus VKAs for the treatment of CVT. [ABSTRACT FROM AUTHOR]

Infective endocarditis (IE) carries a high risk of vascular complications (e.g., cerebral embolism, intracerebral hemorrhage, and renal infarction), which are correlated with increased early and late mortality. Although anticoagulation is the cornerstone for management of thromboembolic complications, it remains controversial and challenging in patients with IE. An appropriate anticoagulation strategy is crucial to improving outcomes and requires a good understanding of the indication, timing, and regimen of anticoagulation in the setting of IE. Observational studies have shown that anticoagulant treatment failed to reduce the risk of ischemic stroke in patents with IE, supporting that IE alone is not an indication for anticoagulation. In the absence of randomized controlled trials and high-quality meta-analyses, however, current guidelines on IE were based largely on observational data and expert opinion, providing few specific recommendations on anticoagulation. A multidisciplinary approach and patient engagement are required to determine the timing and regimen of anticoagulation in patients with IE, especially in specific situations (e.g., receiving warfarin anticoagulation at the time of IE diagnosis, cerebral embolism or ischemic stroke, intracerebral hemorrhage, or urgent surgery). Collectively, individualized strategies on anticoagulation management of IE should be based on clinical evaluation, available evidence, and patient engagement, and ultimately be developed by the multidisciplinary team. [Display omitted] • Infective endocarditis carries a high risk of vascular complications (embolic & hemorrhagic). • Infective endocarditis alone is not an indication for anticoagulation. • Anticoagulation must be balanced between least risks for embolic and hemorrhagic complications. • Anticoagulation should be individualized and ultimately be directed by multidisciplinary team. [ABSTRACT FROM AUTHOR]

Background: Both valvular heart disease (VHD) and atrial fibrillation (AF) frequently coexist. AF is an important cause of arrhythmias with a definitive cardiovascular morbidity. The use of either vitamin K antagonists (VKAs/warfarin) or direct oral anticoagulants (DOACs) (also known as new oral anticoagulants (NOACs)) has been the mainstay for preventing stroke and systemic embolism in patients with VHD and/or AF, and this has been broadly discussed. However, there are limited studies on anticoagulation therapy for patients with valvular atrial fibrillation (VAF). The main aim of this meta-analysis was to evaluate the outcomes (stroke–vascular events and intracranial bleeding) following DOAC and VKA treatment amongst patients with VAF. Methods: We identified clinical trials and observational studies published in the last 10 years. A systematic review and a meta-analysis were performed to evaluate the outcomes of patients with valvular atrial fibrillation following DOAC vs. VKA treatment. Data evaluation was performed using Review Manager 5.4; the endpoints were stroke–vascular events and intracranial bleeding following DOAC and VKA treatment amongst VAF patients. Risk ratios (RR) were evaluated with 95% confidence intervals. Using random effects models, forest plots were obtained. Heterogeneity was assessed by using the I2 statistic. Results: Eight studies were included in this metanalysis, and a total of fifteen thousand two hundred and fifteen patients (DOAC (8732) and VKA (6483)) were pooled. We found a significant risk reduction in stroke–vascular events when using DOACs in comparison with using VKAs (pooled RR: 0.76; 95% CI: 0.64–0.90, p = 0.002). A total of 14862 patients (DOAC (8561) and VKA (6301)) were pooled from a total of six studies for intracranial bleeding. We found a significant risk reduction in terms of intracranial bleeding when using DOACs in comparison with using VKAs (pooled RR: 0.43; 95% CI: 0.24–0.77, p ≤ 0.05). Conclusions: When compared to VKAs, DOAC agents were found to have less risk of stroke–vascular events and intracranial bleeding. Further prospective studies are essential to establish the efficacy and safety of DOAC agents in patients with various subtypes of VAF. [ABSTRACT FROM AUTHOR]

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[Display omitted] [ABSTRACT FROM AUTHOR]

Abstract Background and Aims Current clinical guidelines for treating left ventricular thrombus (LVT) are limited by inadequate evidence to inform the comparative efficacy of oral anticoagulants. In this meta‐analysis, we aimed to compare the efficacy and safety of direct oral anticoagulants (DOAC) to vitamin K antagonists (VKA) in patients with LVT. Methods Four standard databases were searched for relevant literature comparing the efficacy and safety between DOAC and VKA for LVT treatment, published before August 19, 2023. Both the randomized controlled trials and observational studies were included in the analysis. The outcomes of interest were the resolution of LVT, all‐cause mortality, stroke, systemic embolism, and bleeding. Data from the selected studies were extracted and analyzed using RevMan 5.4 using odds ratio. Results Among 3959 studies from the database search and bibliography review, 33 were included in the analysis. LVT resolution was observed in 72.59% in the DOAC group versus 67.49% in the VKA group (odds ratio [OR]: 1.28, confidence interval [CI]: 1.07–1.53). Mortality was lower in the DOAC group (11.71% vs. 18.56%) (OR: 0.60, CI: 0.36–1.00; borderline statistical significance). Likewise, bleeding events (9.60% vs. 13.19%) (OR: 0.65, CI: 0.52–0.81) and stroke (7.54% vs. 11.04%) (OR: 0.71, CI: 0.53–0.96) were also significantly lower in the DOAC group. Conclusion DOAC use for LVT showed better thrombus resolution and reduced risk of bleeding and stroke compared to VKA. Likewise, DOAC use was associated with lower mortality with borderline statistical significance.

IntroductionCurrent guidelines recommend that patients with cerebral venous thrombosis (CVT) should be treated with vitamin K antagonists (VKAs) for 3–12 months. Direct oral anticoagulants (DOACs), however, are increasingly used in clinical practice. An exploratory randomized controlled trial including 120 patients with CVT suggested that the efficacy and safety profile of dabigatran (a DOAC) is similar to VKAs for the treatment of CVT, but large-scale prospective studies from a real-world setting are lacking.MethodsDOAC-CVT is an international, prospective, observational cohort study comparing DOACs to VKAs for the prevention of recurrent venous thrombotic events after acute CVT. Patients are eligible if they are 18 years or older, have a radiologically confirmed CVT, and have started oral anticoagulant treatment (DOAC or VKA) within 30 days of CVT diagnosis. Patients with an absolute contra-indication for DOACs, such as pregnancy or severe renal insufficiency, are excluded from the study. We aim to recruit at least 500 patients within a three-year recruitment period. The primary endpoint is a composite of recurrent venous thrombosis and major bleeding at 6 months of follow-up. We will calculate an adjusted odds ratio for the primary endpoint using propensity score inverse probability treatment weighting.DiscussionDOAC-CVT will provide real-world data on the comparative efficacy and safety of DOACs versus VKAs for the treatment of CVT.Clinical trial registrationClinicalTrials.gov, NCT04660747.

Background: Direct oral anticoagulants (DOACs) are associated with bleeding. Patients often stop taking DOACs due to non-major bleeding, which may lead to stroke recurrence. We aimed to determine the risk of non-major bleeding using different DOACs to prevent strokes in atrial fibrillation (AF). Methods: A systematic search of four databases (PubMed, EMBASE, Web of Science, and Cochrane Library) was performed to identify randomized controlled trials (RCTs) reporting non-major bleeding events in patients taking DOACs or vitamin K antagonists (VKAs). In this frequency-based network meta-analysis, odds ratios and 95% confidence intervals were used for reporting. Based on the surface under the cumulative ranking curves (SUCRA), the relative ranking probability of each group was generated. Results: Nineteen randomized controlled trials (RCTs) (involving 85,826 patients) were included. For clinically relevant non-major bleeding, the risk for bleeding was lowest for apixaban (SUCRA, 93.9), followed by that for VKAs (SUCRA, 47.7), dabigatran (SUCRA, 40.3), rivaroxaban (SUCRA, 35.9), and edoxaban (SUCRA, 32.2). The minor bleeding safety of DOACs was ranked from highest to lowest as follows: apixaban (SUCRA, 78.1), edoxaban (SUCRA, 69.4), dabigatran (SUCRA, 48.8), and VKAs (SUCRA, 3.7). Conclusions: Based on current evidence, for stroke prevention in patients with AF, the safest DOAC is apixaban in terms of non-major bleeding. This suggests that apixaban may have a lower risk of non-major bleeding than other anticoagulants and may help provide some clinical reference for choosing a more appropriate drug for the patient. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) patients are more susceptible to dementia, but the results about the effect of oral anticoagulants (OACs) on the risk of dementia are not consistent. We hypothesize that OAC is associated with a reduced risk of dementia with AF and that nonvitamin K antagonist oral anticoagulants (NOAC) are superior to vitamin K antagonists (VKA). Four databases were systematically searched until July 1, 2022. Two reviewers independently selected literature, evaluated quality, and extracted data. Data were examined using pooled hazard ratios (HRs) and 95% confidence intervals (CIs). Fourteen research studies involving 910 patients were enrolled. The findings indicated that OACs were associated with a decreased risk of dementia (pooled HR: 0.68, 95% CI: 0.55–0.82, I2 = 87.7%), and NOACs had a stronger effect than VKAs (pooled HR: 0.87, 95% CI: 0.79–0.95, I2 = 72%), especially in participants with a CHA2DS2VASc score ≥ 2 (pooled HR: 0.85, 95% CI: 0.72–0.99). Subgroup analysis demonstrated no statistical significance among patients aged <65 years old (pooled HR: 0.83, 95% CI: 0.64–1.07), patients in "based on treatment" studies (pooled HR: 0.89, 95% CI: 0.75–1.06), or people with no stroke background (pooled HR: 0.90, 95% CI: 0.71–1.15). This analysis revealed that OACs were related to the reduction of dementia incidence in AF individuals, and NOACs were better than VKAs, remarkably in people with a CHA2DS2VASc score ≥ 2. The results should be confirmed by further prospective studies, particularly in patients in "based on treatment" studies aged <65 years old with a CHA2DS2VASc score < 2 or without a stroke background. [ABSTRACT FROM AUTHOR]

Aims: Patients after heart transplantation (HTX) often require oral anticoagulants (OACs) due to atrial arrhythmias or thromboembolic events but little is known about the post-transplant use of direct oral anticoagulants (DOACs). We investigated the frequency, indications, and complications of DOACs and vitamin K antagonists (VKAs) after HTX. Methods: We screened all adult patients for the use of post-transplant OACs who underwent HTX at Heidelberg Heart Center between 2000 and 2021. Patients were stratified by type of OAC (DOAC or VKA) and by DOAC agents (apixaban, dabigatran, edoxaban, or rivaroxaban). Indications for OACs comprised atrial fibrillation, atrial flutter, pulmonary embolism, upper and lower extremity deep vein thrombosis, as well as intracardiac thrombus. Results: A total of 115 of 459 HTX recipients (25.1%) required OACs, including 60 patients with DOACs (52.2%) and 55 patients with VKAs (47.8%). Concerning DOACs, 28 patients were treated with rivaroxaban (46.7%), 27 patients with apixaban (45.0%), and 5 patients with edoxaban (8.3%). We found no significant differences between both groups concerning demographics, immunosuppressive drugs, concomitant medications, indications for OACs, ischemic stroke, thromboembolic events, or OAC-related death. Patients with DOACs after HTX had a significantly lower one-year rate of overall bleeding complications (p = 0.002) and a significantly lower one-year rate of gastrointestinal hemorrhage (p = 0.011) compared to patients with VKAs after HTX in the Kaplan–Meier estimator. Conclusions: DOACs were comparable to VKAs concerning the risk of ischemic stroke, thromboembolic events, or OAC-related death but were associated with significantly fewer bleeding complications in HTX recipients. [ABSTRACT FROM AUTHOR]

Background: The relative effectiveness of anticoagulation agents in patients with atrial fibrillation (AF) who survive an intracranial hemorrhage (ICH) is unknown. This study was performed to examine the comparative effectiveness of different oral anticoagulation (OAC) on clinical outcomes in this group of patients. Methods: We performed a Bayesian network meta-analysis of randomized controlled trials (RCTs) and observational studies comparing different OAC (direct oral anticoagulant [DOAC] and warfarin) for the treatment of patients with AF who sustained ICH. Outcomes included repeat ICH, thromboembolic events, and all-cause mortality. The values derived from the surface under the cumulative ranking curve were obtained to rank the treatment hierarchy. Results: We identified 12 studies (two RCTs and ten observational studies) involving 23,265 patients; 346 patients were treated with any OAC agents; 5,006 received DOAC; 5,271 received warfarin; 12,007 received antiplatelet or no therapy, and 635 did not received relevant therapy. Both DOAC and warfarin (RR, 0.58; 95% CI, 0.45–0.74; RR, 0.83; 95% CI, 0.69–0.98) were superior to antiplatelet or no therapy in preventing thromboembolic events. Moreover, DOAC also showed superiority in preventing thromboembolic events (RR, 0.70; 95% CI, 0.58–0.83), repeat ICH (RR, 0.52; 95% CI, 0.40–0.67), and all-cause mortality (RR, 0.51; 95% CI, 0.46–0.56) than warfarin. Conclusions: Our study suggests DOACs may be a reasonable alternative to anti-platelet therapy and warfarin for patients with AF who experienced ICH. However, given the available evidence is primarily observational, further validation by ongoing trials directly comparing these two classes of drugs are needed. [ABSTRACT FROM AUTHOR]

Abstract Aims Left ventricular thrombus (LVT) increases the risk of thrombotic events and mortality. Vitamin K antagonists (VKAs) used to treat LVT have several known risks, as a result of which direct oral anticoagulant (DOAC) use has recently increased. We aimed to evaluate the safety and efficacy of DOACs and VKAs in treating LVT. Methods and results We searched PubMed, Embase, Cochrane Library trials, and Web of Science databases for studies published before 19 April 2022, involving DOAC versus VKA treatment for patients with LVT. This meta‐analysis comprised 21 studies (total patients, n = 3172; DOAC group, n = 888; VKA group, n = 2284). A statistically significant reduction in bleeding events was observed in patients on DOACs vs. those on VKAs (risk ratio (RR) = 0.73, P = 0.004). Patients on DOACs residing in North American and European regions and those with ischaemic heart disease (IHD) had a significantly lower risk of bleeding events than patients residing in other regions or those with a different LVT aetiology, respectively (RR = 0.78, P = 0.04; RR = 0.38, P = 0.02; and RR = 0.63, P = 0.009). A statistically significant reduction in stroke in patients on DOACs versus VKAs (RR = 0.72, P = 0.03) was observed, and patients on DOACs residing in North America and those with IHD had a significantly lower risk of stroke (RR = 0.73, P = 0.04, and RR = 0.61, P = 0.03, respectively). Compared with VKAs, DOACs are statistically associated with an increase in LVT resolution at 1 month (RR = 1.96, P = 0.008). No statistical between‐group difference in all‐cause mortality (RR = 0.72, P = 0.05), systemic embolism (RR = 0.87, P = 0.74), stroke or systemic embolism (RR = 0.90, P = 0.50), and LVT resolution at the end of follow‐up (RR = 1.06, P = 0.13) was observed. Conclusions Compared with VKAs, DOACs significantly reduce the risk of bleeding events and stroke in LVT patients, but mortality was similar in both groups. The advantages are apparent not only in patients belonging to the predominantly white residential areas such as North American and European regions but also in patients with LVT due to IHD. DOACs show promising effects in treating LVT compared with VKAs.