Bleeding risk in patients with atrial fibrillation treated with combined anti-platelet and non-vitamin K antagonist oral anticoagulant therapy.

BACKGROUND: The use of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with non-valvular atrial fibrillation (AF) has been increasing. Accordingly, the combined use of antiplatelet agents (APT) and NOAC therapy is commonly encountered in clinical practice. The purpose of this study was to compare the clinical outcomes between combination therapy (NOAC and APT) vs. monotherapy (NOAC only) in patients with AF. METHODS: We retrospectively analyzed patients who were prescribed NOACs between January 2012 and December 2016. The primary outcome was major bleeding and any bleeding events, and the secondary outcomes were stroke/systemic embolic (SE) events and major adverse cardiac events (MACE). RESULTS: Of the 1068 participants, there were 264 (24.7%) patients in the combination therapy group. The prevalence of diabetes (p = 0.017) and history of stroke and transient ischemic attacks (p < 0.001) was higher in the combination group than in the monotherapy group. During the mean 14.6 ± 9.8 months of follow-up, the incidence of any bleeding was significantly higher in the combination therapy group than in the monotherapy group (p < 0.001). The rate of major bleeding, stroke/SE, and MACE between the two groups was similar. The rate of under-dosage NOAC prescriptions was higher in the combination therapy group than in the monotherapy group (p = 0.024). CONCLUSIONS: The combination therapy group had higher incidences of any bleeding events compared to the monotherapy in patients with appropriate dosing. However, there was no difference in stroke/SE, and MACE. The bleeding risk in AF patients taking the combination of NOACs and APT should be carefully evaluated.

Patient factors associated with receiving reversal therapy in oral anticoagulant-related intracerebral hemorrhage.

BACKGROUND: We aimed to describe baseline characteristics of patients with oral anticoagulant-related intracerebral hemorrhage (OAC-ICH) in Sweden and to identify predictive variables associated with receiving hemostatic treatment in the event of OAC-ICH. METHODS: We performed an observational study based on data from Riksstroke and the Swedish Causes of Death Register to define baseline characteristics of patients with OAC-ICH who received reversal treatment compared with patients who did not receive reversal treatment during 2017-2019. Predictive analysis was performed using multivariable logistic regression to identify odds ratios for factors associated with receiving OAC reversal treatment. RESULTS: We included 1902 patients ((n = 1146; OAC reversal treatment) (n = 756; no OAC reversal treatment)). The proportion of non-Vitamin K oral anticoagulant associated ICH (NOAC-ICH) patients who received reversal treatment was 48.4% and the proportion of Vitamin K antagonist-associated ICH (VKA-ICH) patients was 72.9%. Factors associated with a lower odds of receiving reversal treatment were increased age (OR = 0.98; 95% CI: 0.96-0.99), previous stroke (OR = 0.78; 95% CI: 0.62-0.98), comatose LOC (OR = 0.36;95%CI: 0.27-0.48; ref. = alert), pre-stroke dependency (OR = 0.72; 95% CI: 0.58-0.91), and NOAC treatment (OR = 0.34; 95% CI: 0.28-0.42). Care at a university hospital was not associated with higher odds of receiving reversal treatment compared to treatment at a county hospital. CONCLUSION: Treatment with a reversal agent following OAC-ICH was related to several patient factors including type of OAC drug. We identified that only 48% of patients with NOAC-ICH received hemostatic treatment despite an increase in these cases. Further studies are required to guide the use of reversal therapies more precisely, particularly in NOAC-ICH.

The impact on renal function after long-term use of anticoagulants in atrial fibrillation patients.

OBJECTIVE: Long-term oral anticoagulant should be considered or recommended in patients with atrial fibrillation (AF) and CHA2DS2VASc score ≥ 1 for stroke prevention. Warfarin and different direct oral anticoagulants (DOACs) are metabolized differently by the kidney. The impact on renal function after long-term use of anticoagulants in the patients with AF remains unclear. This study aimed to compare DOACs and warfarin's impact on the decline in renal function from a large cohort with AF. METHODS: This study included patients with nonvalvular AF from 2000 to 2018, mainly through the medical history (ICD code) of the Chang Gung Research Database. Baseline estimated glomerular filtration rate (eGFR), follow-up eGFR and the change in eGFR between 2-year eGFR and baseline eGFR were compared between different DOACs and warfarin after propensity score matching. The primary study endpoint was acute kidney injury (AKI). RESULTS: 3657 patients were enrolled in this study and the mean observation time was 3.3 ± 0.9 years. During the observation period, there was a significantly higher incidence of AKI during follow-up in the warfarin group than in the different DOAC groups before and after propensity score matching (before: warfarin vs. DOAC: 9.2% vs. 5.2%, p <  0.001; after: warfarin vs. DOAC: 8.9% vs. 4.4%, p <  0.001). There was no difference in the incidence of AKI between dabigatran group and anti-factor Xa inhibitor group after propensity score matching. The incidence of AKI was similar among rivaroxaban, apixaban and edoxaban groups after propensity score matching. The change in eGFR between 2-year eGFR and baseline eGFR did not differ between the warfarin and DOAC groups after propensity score matching (warfarin vs. DOAC: - 1.27 ± 20.32 vs. -1.94 ± 17.24 mL/min/1.73 m2, p = 0.461). CONCLUSIONS: During the mean observation time of 3.3 ± 0.9 years, warfarin was associated with a higher incidence of AKI compared with DOACs. The decline in renal function did not differ among warfarin and different DOAC groups.

Outcome of non-vitamin K oral anticoagulants in the treatment of left atrial/left atrial appendage thrombus in patients with nonvalvular atrial fibrillation.

BACKGROUND: Data comparing dabigatran with rivaroxaban regarding the resolution of left atrial/left atrial appendage (LA/LAA) thrombus in patients with nonvalvular atrial fibrillation (AF) are scarce. This study aimed to compare the efficacy and safety of dabigatran vs rivaroxaban regarding the resolution of LA/LAA thrombus in patients with nonvalvular AF. METHODS: This retrospective study enrolled nonvalvular AF patients scheduled to undergo catheter ablation or cardioversion in Shanghai Ruijin Hospital between January 2014 and January 2019. Altogether, 34 patients with LA/LAA thrombus detected by transesophageal echocardiography (TEE) were enrolled. Among them, 12 patients were treated with dabigatran 150 mg bid and the other 22 with rivaroxaban 20 mg qd. Follow-up TEE was performed within greater than or equal to 3 weeks to less than 6 months of the initial TEE to evaluate the resolution of the LA/LAA thrombus. RESULTS: Baseline patient characteristics were similar in the two groups. Overall, 18 patients (81.8%) in the rivaroxaban group had complete thrombus resolution after 70.3 ± 22.1 treatment days, and 10 patients (83.3%) in the dabigatran group had complete thrombus resolution after 69.3 ± 47.9 treatment days. There was no significant difference between the groups (P = .6). TEE showed that the average length, width, and area of thrombus significantly decreased in both groups after treatment, although there was no significant difference in the amount of change in these parameters between the two groups after treatment (P = .6). Undissolved thrombus in two patients in the rivaroxaban group did dissolve after switching to dabigatran. CONCLUSIONS: The results suggest that both dabigatran and rivaroxaban are potential options for treating LA/LAA thrombus in patients with nonvalvular AF. Dabigatran could be an alternative option for the resolution of LA/LAA thrombus resistant to rivaroxaban.

Blood Pressure and Anticoagulation Reversal Management during Off-Hours in Oral Anticoagulation-Associated Intracerebral Hemorrhage.

BACKGROUND: Prevention of hematoma enlargement in oral anticoagulation-associated intracerebral hemorrhage (OAC-ICH) focuses on blood pressure (BP) reduction and OAC reversal. We investigated whether treatment efficiency and clinical outcomes differ between OAC-ICH patients admitted outside versus during regular working hours. METHODS: Based on pooled data of multicenter cohort studies, we grouped OAC-ICH patients (vitamin K antagonist [VKA], non-vitamin K oral anticoagulant [NOAC]) according to on- vs. off-hour admission. Primary outcome was the functional outcome using the modified Rankin scale (mRS) dichotomized into favorable (mRS 0-3) and unfavorable (mRS 4-6) and mortality at 3 months. Secondary outcome measures included the occurrence of hematoma enlargement, the proportions of patients with systolic BP <140 mm Hg and with anticoagulation treatment achieving international normalized ratio (INR) levels <1.3 at 4 h. Propensity score matching (PSM) was performed to account for imbalances in baseline characteristics. RESULTS: The study population consisted of 76/126 NOAC-ICH patients and 1,005/1,470 VKA patients presenting during off-hours. Functional outcome and mortality rates were not significantly different among PSM patients with VKA-ICH and NOAC-ICH during on- vs. off-hours (mRS 4-6 VKA-ICH: on-hour: 239/357 [66.9%] vs. 253/363 [69.7%] off-hour; p = 0.43; NOAC-ICH: on-hour 26/42 [61.9%] vs. off-hour: 37/57 [64.9%]; p = 0.76; mRS 6 VKA-ICH: on-hour: 127/357 [35.6%] vs. off-hour: 148/363 [40.8%]; p = 0.15; -NOAC-ICH: on-hour 17/42 [40.5%] vs. off-hour: 16/57 [28.1%]; p = 0.20). There were no differences detectable regarding the secondary outcome measures (i.e., hematoma enlargement, the proportion of patients who achieved systolic BP levels <140 mm Hg at 4 h as well as anticoagulation treatment achieving INR levels <1.3 at 4 h) in OAC patients. CONCLUSION: Our study implies that BP reduction and anticoagulation reversal management are well established and associated with similar rates of hematoma enlargement and clinical outcomes in on- vs. off-hour admitted OAC-ICH patients.

Anti-Factor Xa Activity of Standard and Japan-Specific Doses of Rivaroxaban in Thai Patients With Non-Valvular Atrial Fibrillation.

BACKGROUND: Recommended rivaroxaban doses for stroke prevention in atrial fibrillation (SPAF) are 20 and 15 mg/day in patients with normal and reduced renal function, respectively, but lower doses (15 and 10 mg) have been tested and approved in Japan. It is not known whether 15 and 10 mg rivaroxaban are appropriate in other Asian populations. This study compared the anti-Factor Xa (FXa) activity of 20 and 15 mg rivaroxaban in Thai patients with normal renal function and 15 and 10 mg rivaroxaban in patients with reduced renal function.Methods and Results:Sixty non-valvular atrial fibrillation patients receiving rivaroxaban (mean [±SD] age 69.3±9.1 years, mean creatinine clearance 59.2±22.7 mL/min) were enrolled. The anti-FXa activity of standard rivaroxaban and Japan-specific doses was measured at peak and trough concentrations. Median anti-FXa activity at peak concentrations was significantly higher for the standard than Japan-specific dose. Median anti-FXa activity measured at the trough was significantly higher for the standard dose only in those with impaired renal function. A higher proportion of patients receiving the Japan-specific rather than standard dose had anti-FXa activity at peak concentrations within the expected range (87.7% vs. 64.4%; P=0.001). One-third of those receiving the standard dose had anti-FXa activity higher than the expected range. CONCLUSIONS: A significantly higher proportion of Thai patients receiving the Japan-specific dose of rivaroxaban had anti-FXa activity at peak concentrations within the expected range.

Periprocedural anticoagulation in atrial fibrillation: Update on electrical cardioversion and ablation.

In this manuscript, we discuss the most important changes in the field of anticoagulant treatment in patients with atrial fibrillation in the setting of electrical cardioversion or catheter ablation. Moreover, we provide practical guidance as well as information on daily practice.

Anti Xa oral anticoagulants inhibit in vivo platelet activation by modulating glycoprotein VI shedding.

Anti Xa non-vitamin K oral anticoagulants (anti Xa NOACs) seem to possess antiplatelet effect in vitro, but it is unclear if this occurs also in vivo. Aim of the study was to compare the effect on platelet activation of two anti Xa NOACs, namely apixaban and rivaroxaban, to warfarin, and to investigate the potential underlying mechanism by evaluating soluble glycoprotein GPVI (sGPVI), a protein involved in platelet activation. We performed a cross-sectional including AF patients treated with warfarin (n=30), or apixaban 10mg/day (n=40), or rivaroxaban 20mg/day (n=40). Patients were balanced for sex, age and cardiovascular risk factors. Platelet activation by urinary excretion of 11-dehydro-thromboxane (Tx) B2 and soluble GPVI (sGPVI) were analysed at baseline and after 3 months of treatment. Baseline TxB2 value was 155.2±42.7ng/mg creatinine. The 3 months-variation of urinary excretion of TxB2 was -6.5% with warfarin (p=0.197), -29% with apixaban (p<0.001) and -31% with rivaroxaban (p<0.001). Use of anti Xa NOACs was independently associated to the variation of urinary TxB2 (B: -0.469, p<0.001), after adjustment for clinical characteristics; sGPVI was significantly lower in patients treated with NOACs at 3 months (p<0.001), while only a trend for the warfarin group (p=0.116) was observed. The variation of sGPVI was correlated with that of TxB2 in the NOACs group (Rs: 0.527, p<0.001). In 15 patients (5 per each group) platelet recruitment was significantly lowered at 3 months by NOACs (p<0.001), but not by warfarin. The study provides evidence that anti Xa NOACs significantly inhibit urinary TxB2 excretion compared to warfarin, suggesting that NOACs possess antiplatelet property.

Safety and efficacy of non-vitamin K oral anticoagulant treatment compared with warfarin in patients with non-valvular atrial fibrillation who develop acute ischemic stroke or transient ischemic attack: a multicenter prospective cohort study (daVinci study).

The safety and efficacy of non-vitamin K oral anticoagulant (NOAC) compared with warfarin in treating patients with non-valvular atrial fibrillation (NVAF) who developed acute ischemic stroke or transient ischemic attack (AIS/TIA), particularly those receiving tissue-plasminogen activator (tPA) therapy, remains unclear. Between April 2012 and December 2014, we conducted a multicenter prospective cohort study to assess the current clinical practice for treating such patients. We divided the patients into two groups according to the administration of oral anticoagulants (warfarin or NOACs) and tPA therapy. The risk of any hemorrhagic or ischemic event was compared within 1 month after the onset of stroke. We analyzed 235 patients with AIS/TIA including 73 who received tPA therapy. Oral anticoagulants were initiated within 2-4 inpatient days. NOACs were administered to 49.8 % of patients, who were predominantly male, younger, had small infarcts, lower NIHSS scores, and had a lower all-cause mortality rate (0 vs. 4.2 %, P = 0.06) and a lower risk of any ischemic events (6.0 vs. 7.6 %, P = 0.797) compared with warfarin users. The prevalence of all hemorrhagic events was equivalent between the two groups. Early initiation of NOACs after tPA therapy appeared to lower the risk of hemorrhagic events, although there was no significant difference (0 vs. 5.6 %, P = 0.240). Although more clinicians are apt to prescribe NOACs in minor ischemic stroke, NOAC treatment may provide a potential benefit in such cases. Early initiation of NOACs after tPA therapy may reduce the risk of hemorrhagic events compared with warfarin.

Intracranial bleedings in patients on long-term anticoagulant treatment: Benefits from oral thrombin and factor Xa inhibitors in clinical practice.

Dabigatran, a direct thrombin inhibitor and activated factor X inhibitors, rivaroxaban and apixaban, used in the prevention of stroke or systemic embolism in patients with nonvalvular atrial fibrillation (AF), have several advantages over vitamin K antagonists (VKAs). The non-vitamin K oral anticoagulants (NOACs) have been shown to reduce the risk of intracranial bleedings by 50%. The current review summarizes the available data on the epidemiology, mechanisms and treatment of intracranial bleedings observed on oral anticoagulation with the focus on the specificity of NOACs in this context.

Risk of gastrointestinal bleeding in Asian patients receiving oral anticoagulants for stroke prevention in atrial fibrillation.

Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used for stroke prevention in atrial fibrillation. At the Asia Pacific Advancing Patient care with EdoXaban 2023 meeting, experts shared insights on gastrointestinal bleeding with NOACs for stroke prevention in atrial fibrillation in Asian clinical practice, where NOACs have gained widespread acceptance due to their favourable profiles. Gastrointestinal bleeding risk varies amongst NOACs, emphasizing the importance of diligent patient assessment, dosage selection and vigilant monitoring. Edoxaban emerged as a viable option with a low gastrointestinal bleeding risk profile in Asian compared with non-Asian patients, supporting its continued clinical utilization for appropriate patients.

Design, Rationale and Initial Findings From HERA-FIB on 10 222 Patients With Atrial Fibrillation Presenting to an Emergency Department Over An 11-Year Period.

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.

Contemporary trends and barriers to oral anticoagulation therapy in Non-valvular atrial fibrillation during DOAC predominant era.

There is a need to reassess contemporary oral anticoagulation (OAC) trends and barriers against guideline directed therapy in the United States. Most previous studies were performed before major guideline changes recommended direct oral anticoagulant (DOAC) use over warfarin or have otherwise lacked patient level data. Data on overuse of OAC in low-risk group is also limited. To address these knowledge gaps, we performed a nationwide analysis to analyze current trends. This is a retrospective cohort study assessing non-valvular AF identified using a large United States de-identified administrative claims database, including commercial and Medicare Advantage enrollees. Prescription fills were assessed within a 90-day follow-up from the patient's index AF encounter between January 1, 2016, and December 31, 2020. Among the 339,197 AF patients, 4.4%, 8.0%, and 87.6% were in the low-, moderate-, and high-risk groups (according to CHA2DS2-VASc score). An over (29.6%) and under (52.2%) utilization of OAC was reported in low- and high-risk AF patients. A considerably high frequency for warfarin use was also noted among high-risk group patients taking OAC (33.1%). The results suggest that anticoagulation use for stroke prevention in the United States is still comparable to the pre-DOAC era studies. About half of newly diagnosed high-risk non-valvular AF patients remain unprotected against stroke risk. Several predictors of OAC and DOAC use were also identified. Our findings may identify a population at risk of complications due to under- or over-treatment and highlight the need for future quality improvement efforts.

Treatment of Persistent Left Atrial Appendage Thrombus in Patients with Atrial Fibrillation on Adequate Oral Anticoagulation: Pathways of Care for All-comers and Heart Failure Patients.

In patients with AF, the presence of left atrial/left atrial appendage (LA/LAA) thrombus is related to an increased risk of thromboembolic events. Anticoagulation therapy, either with vitamin K antagonists or novel oral anticoagulants (NOACs) is therefore mandatory in AF with LA/LAA thrombus in order to lower the risk of stroke or other systemic embolic events. Despite the efficacy of these treatments, some patients will have persistent LAA thrombus remaining or may have contraindications to oral anticoagulation. Currently, little is known about the occurrence, risk factors and resolution rate of LA/LAA thrombus in patients who are already under optimal chronic oral anticoagulation, including vitamin K antagonists or NOACs. The common action in clinical practice in this scenario is switching from one to another anticoagulant drug exhibiting a different mechanism of action. Repeated cardiac imaging is then advised within several weeks to visually verify thrombus dissolution. Finally, there is a substantial scarcity of data on the role and optimal use of NOACs after LAA occlusion. The aim of this review is to critically evaluate data and provide up-to-date information on the best antithrombotic strategies in this challenging clinical scenario.

Safety of a single bolus administration of heparin without the measurement of activated clotting time during cryoballoon ablation: a prospective randomized controlled trial.

BACKGROUND: Single-shot ablation has emerged as an effective technique for index atrial fibrillation (AF) ablation, with an advantage of short procedure time. Although recent guidelines recommend peri-procedural uninterrupted oral anticoagulants (OACs), the intra-procedural anticoagulation strategy remains uncertain under non-vitamin K OACs (NOACs). We investigated procedural safety of a single bolus administration of heparin without activated clotting time (ACT) measurement during cryoballoon ablation (CBA). METHODS: Two hundred patients (64.2 ± 10.0 years, 70% with non-paroxysmal AF) who underwent CBA with uninterrupted NOACs were randomly assigned to No-ACT group and ACT group. A bolus of heparin (100 U/kg) was routinely administered immediately after transseptal puncture. In the ACT group, an additional injection of heparin (30 U/kg) was administered if ACT at 30 min after the initial bolus was < 300 s. RESULTS: There were no differences in baseline characteristics including CHA2DS2-VASc score between the two groups. The left atrium indwelling and procedure times were 60.4 ± 13.1 min and 78.9 ± 13.9 min, respectively, and not significantly different between the two groups. The mean ACT was 335.2 ± 59.9 s in the ACT group. Any bleeding rate was 3.2% in all patients and there was no statistically significant difference in bleeding complications between the two groups. In the ACT group, groin hematoma, laryngopharyngeal bleeding, and hemoptysis occurred in 3, 1, and 1 patient, respectively. Cardiac tamponade occurred in 1 patient in the No-ACT group. No thromboembolic events occurred during the 30-day follow-up after CBA. CONCLUSIONS: Single bolus administration of heparin without ACT measurement is a feasible anticoagulation strategy for CBA in patients with uninterrupted NOAC intake.

Short- and Long-Term Mortality for Patients With and Without a Cancer Diagnosis Following Pulmonary Embolism in Denmark, 2000 to 2020: A Nationwide Study.

BACKGROUND: New treatment regimens have been introduced in the past 20 years, which may influence the short- and long-term prognosis for patients with and without a cancer diagnosis following pulmonary embolism. However, newer studies investigating these trends are lacking. Therefore, we aimed to investigate the 30- and 31- to 365-day mortality following pulmonary embolism. METHODS AND RESULTS: Using the Danish nationwide registries, patients with a diagnosis of pulmonary embolism between 2000 and 2020 were included. Age- and sex-standardized 30- and 31- to 365-day mortality was calculated and stratified by cancer status. In total, 60 614 patients (29.6% with recent cancer; mean age, 68.2 years) were included. The 30-day mortality for patients with no recent cancer decreased from 19.1% (95% CI, 17.9%-20.4%) in 2000 to 7.3% (95% CI, 6.7%-8.0%) in 2018 to 2020 (hazard ratio [HR], 0.36 [95% CI, 0.32-0.40]; P<0.001). The 30-day mortality for patients with recent cancer decreased from 32.2% (95% CI, 28.8%-36.6%) to 14.1% (95% CI, 12.7%-15.5%) (HR, 0.38 [95% CI, 0.33-0.44]; P<0.001). The 31- to 365-day mortality for patients with no recent cancer decreased from 12.5% (95% CI, 11.4%-13.6%) to 9.4% (95% CI, 8.6%-10.2%) (HR, 0.73 [95% CI, 0.64-0.83]; P<0.001).The 31- to 365-day mortality for patients with recent cancer remained stable: 39.4% (95% CI, 35.1%-43.7%) to 38.3% (95% CI, 35.9%-40.6%) (HR, 0.97 [95% CI, 0.84-1.12]; P=0.69). CONCLUSIONS: From 2000 to 2020, improvements were observed in 30-day mortality following pulmonary embolism regardless of cancer status. For patients with recent cancer, 31- to 365-day mortality did not improve, whereas a minor improvement was observed for patients without recent cancer.

Recurrent Nonbacterial Thrombotic Endocarditis and Primary Antiphospholipid Antibody Syndrome.

In 2015, a 37-year-old man was referred for evaluation of hypertension and was found to have a mobile structure on the posterior mitral valve leaflet on echocardiography. Laboratory investigations yielded a diagnosis of primary antiphospholipid antibody syndrome (APLS). He underwent excision of the lesion and mitral valve repair. Histology confirmed the diagnosis of nonbacterial thrombotic endocarditis (NBTE). The patient was anticoagulated with warfarin up until 2018, which was substituted for rivaroxaban because of an erratic international normalised ratio. Serial echocardiography up to 2020 was unremarkable. In 2021, he presented with breathlessness and peripheral oedema. Echocardiography demonstrated large vegetation on both mitral valve leaflets. At the operation, vegetations were also evident on the left and noncoronary cusps of the aortic valve and he underwent mechanical aortic and mitral valve replacement. Histology confirmed NBTE. The case is unusual and highlights recurrent NBTE requiring re-do valve surgery.

Atraumatic Splenic Rupture: A Notable Complication of Rivaroxaban Use.

Direct oral anticoagulants (DOACs) are well known to be associated with bleeding complications. However, little is known about their association with atraumatic splenic rupture, a potentially fatal condition. We present the case of a 73-year-old female with paroxysmal atrial fibrillation managed with rivaroxaban who developed a spontaneous atraumatic splenic rupture. This highlights the importance of recognizing this complication in patients without previous risk factors, such as abdominal trauma or infiltrative splenic disease, who are under anticoagulation with DOACs. There is a strong need for further research on this complication's underlying mechanism and management.

Edoxaban for stroke prevention in atrial fibrillation and age-adjusted predictors of clinical outcomes in routine clinical care.

AIMS: Patients with atrial fibrillation (AF) treated with oral anticoagulation still suffer from cardiovascular complications including cardiovascular death, stroke, and major bleeding. To identify risk factors for predicting stroke and bleeding outcomes in anticoagulated patients, we assessed 2-year outcomes in patients with AF treated with edoxaban in routine care. We also report the age-adjusted risk predictors of clinical outcomes. METHODS AND RESULTS: The Edoxaban Treatment in Routine Clinical Practice for Patients With Non-Valvular Atrial Fibrillation (ETNA-AF) Europe (NCT02944019) is a prospective, multi-centre, post-authorisation, observational study with an overall 4-year follow-up conducted in 825 centres enrolling edoxaban-treated patients in 10 European countries. Of the 13 133 patients with AF (mean age: 73.6 ± 9.5 years), 5682 (43.3%) were female. At the 2-year follow-up, 9017/13 133 patients were still on edoxaban; 1830 discontinued treatment including 937 who died (annualised event rate of all-cause death was 3.87%). 518 (2.14%) patients died of cardiovascular causes; 234 (0.97%) experienced major bleeding and 168 (0.70%) experienced stroke or systemic embolic events (SEE). Intracranial haemorrhage was noted in 49 patients (0.20%). History of transient ischaemic attack (TIA) at baseline was the strongest predictor of ischaemic stroke or SEE (Wald χ2: 73.63; P < 0.0001). Low kidney function at baseline was the strongest predictor of major bleeding (Wald χ2: 30.68; P < 0.0001). History of heart failure (HF) was the strongest predictor of all-cause (Wald χ2: 146.99; P < 0.0001) and cardiovascular death (Wald χ2: 100.38; P < 0.0001). CONCLUSION: Patients treated with edoxaban in ETNA-AF-Europe reported low 2-year event rates in unselected AF patients. Prior stroke, reduced kidney function, and HF identify patients at high risk of stroke, bleeding and all-cause/cardiovascular death, respectively.

Non-Vitamin K Antagonists Versus Warfarin in Patients with Atrial Fibrillation and Bioprosthetic Valves: A Systematic Review and Meta-Analysis.

BACKGROUND: Patients with atrial fibrillation and bioprosthetic valves are at high risk for thromboembolic events. The pooled efficacy and safety of non-vitamin K oral anticoagulants (NOACs), as a class, relative to warfarin in this population is not well-known. We aimed to compare the efficacy and safety of NOACs relative to warfarin in patients with bioprosthetic valves or valve repair. METHODS: We systematically searched EMBASE, PubMed, and Cochrane databases for randomized controlled trials comparing NOACs to warfarin in patients with atrial fibrillation and bioprosthetic valves or valve repair. We pooled outcomes for stroke or systemic embolism, ischemic stroke, hemorrhagic stroke, and major bleeding. RESULTS: We included 4 trials with 1379 patients, of whom 723 (52.4%) received a NOAC. Mean follow-up ranged from 90 days to 2.8 years. In the pooled analysis, stroke or systemic embolism was significantly lower in patients treated with NOACs (1.9%) compared with warfarin (3.7%) (odds ratio [OR] 0.43; 95% confidence interval [CI] 0.22-0.85; P = .02). Ischemic stroke (OR 0.72; 95% CI 0.18-2.93), hemorrhagic stroke (OR 0.18; 95% CI 0.03-1.05), cardiovascular death (OR 0.78; 95% CI 0.38-1.62), and all-cause mortality (OR 0.94; 95% CI 0.55-1.62) were not significantly different among groups. Major bleeding was significantly lower in patients treated with NOAC (2.8%) compared with warfarin (4.7%) (OR 0.49; 95% CI 0.28-0.88; P = .02). CONCLUSIONS: In patients with atrial fibrillation and bioprosthetic valves or valve repair, NOACs are associated with a reduced incidence of thromboembolic events and major bleeding as compared with warfarin. Thus, NOACs may be considered a preferred option for this patient population.