Gastrointestinal Bleeding During Direct Oral Anticoagulants Therapy in Patients With Nonvalvular Atrial Fibrillation and Risk of Polypharmacy

Although concomitant medications have been raised as a factor affecting hemorrhage during direct oral anticoagulants (DOACs) therapy, details remain unelucidated. This study was conducted to clarify the relationship between concomitant medications with possible pharmacokinetic interactions and number of concomitant medications, and bleeding and embolism in patients with nonvalvular atrial fibrillation on DOACs. The subjects were 1,010 patients prescribed DOACs between April 2011 and June 2018. The study investigated their course between the first prescription and December 2018, including the presence or absence of clinically relevant bleeding, gastrointestinal bleeding (GIB), and major cardiovascular and cerebrovascular events (MACCE). Impacts of medications were evaluated by the general linear model with inverse probability-weighted propensity score. The observation period was 2,272 patient-years. The rate of bleeding was 4.7%/year, GIB was 2.8%/year, and MACCE was 2.0%/year. Taking 10 or more oral medications concurrently was a significant risk for GIB (hazard ratio, 2.046 [1.188–3.526]; p = 0.010). Nonsteroidal anti-inflammatory drugs (NSAIDs) was the only significant risk for GIB. Clinicians should be aware of gastrointestinal bleeding when using DOACs with patients taking more than 10 medications and/or NSAIDs.

Predictive Value of Left Atrial Appendage Functional Parameters on Left Atrial Thrombus or Spontaneous Echo Contrast in Patients with Nonvalvular Atrial Fibrillation

Background: Left atrial appendage (LAA) spontaneous echocardiographic contrast (SEC), sludge and thrombus were associated with a high incidence of thrombus formation and thromboembolic events in patients with non-valvular atrial fibrillation (AF). We aim to identify the main echocardiographic parameters associated with LAA SEC or LAA sludge/thrombus in nonvalvular AF patients.Methods and results: 298 patients with nonvalvular atrial fibrillation were included in the current study between September 2019 and January 2021. Transthoracic echocardiography and transesophageal echocardiography were performed before scheduled electrical cardioversion. LA diameter and maximum left atrial appendage area were increased in the LAA SEC group than control group, and were further increased in patients with LAA sludge or thrombus. LAA-EV, LAA-FV, anterior mitral annular plane systolic excursion (MAPSE) and LAA FAC were lower in the group with LAA SEC than control group, and were further reduced in LAA sludge or thrombus group. Lower LAA FAC and anterior MAPSE were associated with an increased risk of LAA SEC or LAA sludge/thrombus, and LAA FAC and anterior MAPSE showed high accuracy on predicting LAA SEC or LAA sludge/thrombus.Conclusion: Left atrial appendage FAC and anterior MAPSE improves left atrial appendage stasis in patients with nonvalvular atrial fibrillation.

Barriers to Prescribing Oral Anticoagulants To Inpatients Aged 80 Years and Older With Nonvalvular Atrial Fibrillation: A Cross-Sectional Study

Background: To investigate the temporal trend of prevalence of anticoagulation treatment and explore the factors associated with under prescription of oral anti-coagulants (OACs) among inpatients aged ≥80 years with nonvalvular atrial fibrillation (NVAF). Methods: We retrospectively reviewed the medical records of inpatients with a discharge diagnosis of NVAF from a medical database. We used the Pearson chi-square or Fisher’s exact test to compare categorical variables between patients with and without OACs prescription. Logistic regression analysis was used to assess the association between risk factors and under prescription of OACs. Results: A total of 4375 patients aged ≥80 years with AF were assessed in the largest academic hospital in China from August 1, 2016, to July 31, 2020, 3165 NVAF patients were included. The prevalence of OACs use was 20.9% in 2017, 28.7% in 2018, 35.6% in 2019, and 43.9% in 2020. Of all participants with CHA2DS2-VASc≥2, 1,027 (32.4%) were prescribed OACs; 33.7% and 31.8% of patients with and without prior stroke received OACs, respectively. Age, clinical department where patients were discharged, use of antiplatelets, and history of stroke and dementia were significantly associated with not prescribing OACs. Conclusions: The prevalence of OACs use increased over the past several years. The rate of prescription of OACs was lower among NVAF patients who were older, prescribed antiplatelets, discharged from non-departmental cardiology, and suffered from comorbidities. This study found the iatrogenic factors affecting the use of OACs in the inpatients aged ≥80 years, providing clues and basis for the standardized use of OACs in the inpatients.

Increased expression of six-large extracellular vesicle-derived miRNAs signature for nonvalvular atrial fibrillation

Backgrounds Non-valvular atrial fibrillation (AF) is the most common type of cardiac arrhythmia. AF is caused by electrophysiological abnormalities and alteration of atrial tissues, which leads to the generation of abnormal electrical impulses. Extracellular vesicles (EVs) are membrane-bound vesicles released by all cell types. Large EVs (lEVs) are secreted by the outward budding of the plasma membrane during cell activation or cell stress. lEVs are thought to act as vehicles for miRNAs to modulate cardiovascular function, and to be involved in the pathophysiology of cardiovascular diseases (CVDs), including AF. This study identified lEV-miRNAs that were differentially expressed between AF patients and non-AF controls. Methods lEVs were isolated by differential centrifugation and characterized by Nanoparticle Tracking Analysis (NTA), Transmission Electron Microscopy (TEM), flow cytometry and Western blot analysis. For the discovery phase, 12 AF patients and 12 non-AF controls were enrolled to determine lEV-miRNA profile using quantitative reverse transcription polymerase chain reaction array. The candidate miRNAs were confirmed their expression in a validation cohort using droplet digital PCR (30 AF, 30 controls). Bioinformatics analysis was used to predict their target genes and functional pathways. Results TEM, NTA and flow cytometry demonstrated that lEVs presented as cup shape vesicles with a size ranging from 100 to 1000 nm. AF patients had significantly higher levels of lEVs at the size of 101–200 nm than non-AF controls. Western blot analysis was used to confirm EV markers and showed the high level of cardiomyocyte expression (Caveolin-3) in lEVs from AF patients. Nineteen miRNAs were significantly higher (> twofold, p < 0.05) in AF patients compared to non-AF controls. Six highly expressed miRNAs (miR-106b-3p, miR-590-5p, miR-339-3p, miR-378-3p, miR-328-3p, and miR-532-3p) were selected to confirm their expression. Logistic regression analysis showed that increases in the levels of these 6 highly expressed miRNAs associated with AF. The possible functional roles of these lEV-miRNAs may involve in arrhythmogenesis, cell apoptosis, cell proliferation, oxygen hemostasis, and structural remodeling in AF. Conclusion Increased expression of six lEV-miRNAs reflects the pathophysiology of AF that may provide fundamental knowledge to develop the novel biomarkers for diagnosis or monitoring the patients with the high risk of AF.

The Safety and Efficacy of Standard-Dose versus Low-Dose Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Nonvalvular Atrial Fibrillation and Left Atrial Appendage Thrombus

Background. Data comparing different doses of non-vitamin K antagonist oral anticoagulants (NOACs) regarding resolution of left atrial appendage thrombus (LAAT) in patients with nonvalvular atrial fibrillation (AF) are scarce. This study aimed to investigate the safety and efficacy of standard-dose versus low-dose NOACs in patients with nonvalvular AF and LAAT. Methods. Patients with nonvalvular AF who underwent transesophageal echocardiography (TEE) before interventional procedures for the detection of LAAT and treated with NOACs from October 2014 to September 2020 in Ningbo First Hospital were retrospectively screened. The study population was divided into two groups according to the doses of NOACs: standard-dose group (dabigatran 150 mg, twice daily; rivaroxaban 20 mg, once daily) and low-dose group (aged ≥75 years, body weight <50 kg, or creatinine clearance <50 mL/min; dabigatran 110 mg, twice daily; rivaroxaban 15 mg, once daily). Repeated TEE was performed 1, 2, and 3 months later. The rate of LAAT completely resolved and incidence of thromboembolic and major bleeding events were compared between the two groups. Results. A total of 24 patients were included, 14 patients in the standard-dose group and 10 in the low-dose group. After 3 months, LAAT was completely resolved in 12 out of 14 (85.7%) and 8 out of 10 (80%) patients treated with standard- and low-dose NOACs, respectively. The rate of LAAT completely resolved was comparable between groups. No thromboembolic or major bleeding events occurred during the follow-up. Conclusion. Low-dose NOACs are a safe and effective option for the treatment of LAAT in some special subset patients. However, the results warrant validation in a prospective study.

Problems of adherence to treatment with oral anticoagulants in elderly patients with atrial fibrillation in the Kyrgyz Republic

Objectives assessment of adherence to treatment in elderly patients with nonvalvular atrial fibrillation who were prescribed anticoagulant therapy with vitamin K antagonist, warfarin, and a new oral anticoagulant rivaroxaban. Material and methods. During the study, 322 patients with atrial fibrillation of nonvalvular etiology were observed. Depending on the type of anticoagulant taken, the patients were divided into 2 groups: the first group included 253 (78.6%) people who took warfarin, the second group 69 (21.4%) people, who were prescribed a new oral anticoagulant rivaroxaban. Results. By the end of the one-year follow-up from the start of anticoagulant treatment, only 8.7% of patients in the first group followed the doctor's prescription; the second group had 59.4% of adherent patients. The vast majority of patients refused warfarin therapy due to the inability to control INR. In the case of the appointment of rivaroxaban, the reason for the refusal to take was the high cost of the drugs. Conclusion. Effective prevention of thromboembolic complications in atrial fibrillation requires the development of appropriate measures to improve adherence to treatment.