Risk of Bleeding after Colorectal Endoscopic Resection in Patients with Continued Warfarin Use Compared to Heparin Replacement: A Propensity Score Matching Analysis

The Japan Gastroenterological Endoscopy Society (JGES) guidelines recommend continued warfarin treatment during gastroenterological endoscopic procedures with a high risk of bleeding as an alternative to heparin replacement in patients on warfarin therapy. However, there is insufficient evidence to support the use of warfarin in colorectal endoscopic resection (ER). The present study is aimed at verifying the risk of bleeding after ER for colorectal neoplasia (CRN) in patients with continued warfarin use. This was a single-center retrospective cohort study using clinical records. We assessed 126 consecutive patients with 159 CRNs who underwent ER (endoscopic mucosal resection, 146 cases; endoscopic submucosal dissection, 13 cases) at Hiroshima University Hospital between January 2014 and December 2019. Patients were divided into two groups: the heparin replacement group (79 patients with 79 CRNs) and the continued warfarin group (47 patients with 80 CRNs). One-to-one propensity score matching was performed to compare the bleeding rate after ER between the groups. The rate of bleeding after ER was significantly higher in the heparin replacement group than in the continued warfarin group for both before (10.1% vs. 1.3%, respectively; P = 0.0178 ) and after (11.9% vs. 0%, respectively; P = 0.0211 ) propensity score matching. None of the patients experienced thromboembolic events during the perioperative period. The risk of bleeding after colorectal ER was significantly lower in patients with continued warfarin use than in those with heparin replacement. Our data supports the recommendations of the latest JGES guidelines for patients receiving warfarin therapy.

Direct Oral Anticoagulants versus Warfarin in Octogenarians with Nonvalvular Atrial Fibrillation: A Systematic Review and Meta-Analysis

Direct oral anticoagulants (DOACs) have been demonstrated to be more effective and safer than vitamin-K antagonist (VKA) for stroke prevention in patients with nonvalvular atrial fibrillation (AF). This meta-analysis aims to assess the effect of DOACS vs. VKA in patients ≥ 80 and AF. Primary endpoints were stroke or systemic embolism and all-cause death. Secondary endpoints included major bleeding, intracranial bleeding, and gastrointestinal bleeding. A random-effects model was selected due to significant heterogeneity. A total of 147,067 patients from 16 studies were included, 71,913 (48.90%) treated with DOACs and 75,154 with VKA (51.10%). The stroke rate was significantly lower in DOACs group compared with warfarin group (Relative risk (RR): 0.72; 95% confidence interval (CI): 0.63–0.82; p < 0.001). All-cause mortality was significantly lower in DOACs group compared with warfarin group (RR: 0.82; 95% CI: 0.70–0.96; p = 0.012). Compared to warfarin, DOACs were not associated with reductions in major bleeding (RR: 0.85, 95% CI 0.69–1.04; p = 0.108) or gastrointestinal bleeding risk (RR: 1.08, 95% CI 0.76–1.53; p = 0.678) but a 43% reduction of intracranial bleeding (RR: 0.47, IC 95% 0.36–0.60; p < 0.001) was observed. Our meta-analysis demonstrates that DOACs are effective and safe with statistical superiority when compared with warfarin in octogenarians with AF.

Bleeding Outcomes Using Novel Oral Anticoagulants (NOACs) in End-Stage Renal Disease (ESRD) Versus Coumadin

Background: Patients with end-stage renal disease (ESRD) have been excluded from pivotal clinical trials with novel oral anticoagulants (NOACs). These patients are both at increased risk of venous and arterial thromboembolism and the risk of bleeding is also elevated, thus making treating such patients a challenge. Patients with ESRD and atrial fibrillation (AF) additionally have an increased risk of stroke, compared with less severe renal impairment. The risk of venous thromboembolism (VTE) is also positively correlated with CKD, suggesting ESRD is a hypercoagulable stage. Vitamin K antagonists (VKAs) such as warfarin are the mainstay of treatment as prevention or treatment of thromboembolic disease in ESRD, although the use is highly debated. Randomized controlled trials (RCTs) evaluating DOACs in AF all demonstrated non-inferiority for stroke or side effects, however these studies excluded patients on hemodialysis (HD) and those with creatinine clearance less than 25-30. There appears to be a dearth of high-quality evidence regarding use of DOACs in patients with ESRD. This retrospective analysis aims to evaluate whether use of NOACS causes increased bleeding rates compared to warfarin in the specific population of ESRD patients. Methods: Our study was a retrospective analysis of data using chart review of patients from an urban community medical center between the years 2017-2020. Retrospective data was entered into an electronic data form. Patients required a documented diagnosis of ESRD on hemodialysis and must have received at least one dose of anticoagulation to be included in analysis. Retrospective data pertaining to bleeding events were extracted for this analysis, including GI bleeding, intracranial bleeding, or any other major bleeding. Major bleeding events were defined as those requiring hospitalization or blood transfusion, or any other specific medical intervention. Demographics and clinical variables were presented using frequency and percentages. Patients were stratified into two groups, NOAC use and warfarin use. Continuous variables were analyzed using independent T test while chi square test was used for categorical variables. A p value &lt;0.05 was considered statistically significant. Results: A total sample of 208 patients with ESRD on dialysis who had received anticoagulation were included in this analysis. 51% of patients were male and the majority were African American (79%). The mean age was 67. 43% of patients were on NOACs while 57% were on warfarin. Several other clinical factors were also recorded, with 38% of patients being obese, 92% with hypertension, 58% with diabetes, 45% with coronary artery disease, and 67% with atrial fibrillation. Bleeding outcomes were recorded for both patients who had received a NOAC or warfarin. 24 bleeding events were noted in NOAC group versus 44 events in the warfarin group. There was a higher rate of any major bleeding in the warfarin group versus NOAC group (37% vs 27%), however this not statistically significant (p=0.138) Limitations: More data will need to be collected to gain statistical significance of primary endpoint findings, and we have estimated that a total of approximately 680 patient outcomes would need to be analyzed to gain statistical significance. This data collection is currently underway. Other limitations include the retrospective nature of this study, with heavy reliance on review of patient charts for proper documentation of clinically relevant bleeding while on anticoagulation. Ideally, a prospective study would be better able to standardize data. Conclusions: Based on current data analysis, there is a trend towards warfarin having higher rates of bleeding compared to DOACs in ESRD patients on dialysis, 37% versus 27%, although this is only approaching statistical significance. These findings may shift current lines of thought that warfarin is a more acceptable choice of anticoagulation in ESRD patients given long term experience with this drug. Further studies are needed to make more definite conclusions. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Rivaroxaban versus Warfarin in the Management of Deep Venous Thrombosis

Background Deep venous thrombosis (DVT) refers to the formation of one or more blood clots in one of the body’s large veins, most commonly in the lower limbs. The clot can cause partial or complete blocking of circulation in the vein, which in some patients leads to pain, swelling, tenderness, discolouration of the skin that is warm to touch. Aim of the Work Compare the effect of direct Oral Anticoagulant (Rivaroxaban) versus Antivitamin K (warfarin) in treatment of lower limb Deep Venous Thrombosis. Patients and Methods Type of study: prospective single blinded randomized study, study setting: was conducted at Kobri Elkobba hospitals, study period: 6 months, study population: Eligible all patients above 18 years had femoropopliteal vein thrombosis, confirmed with duplex ultrasound scanning and D-dimer test and qualified under the inclusion and exclusion criteria of the study. Results Our study shows that Rivaroxaban alone is as effective as standard therapy, with similar safety, for the treatment of acute DVT and in preventing recurrence and has low risk of bleeding. There was statistically significant increase in INR monitoring during 6 months in warfarin group than Rivaroxaban group with p-value &lt; 0.001. This because warfarin has many drug and food interaction. There's no response in treatment out come after 3 months duplex as the study was on patient of femoro popliteal DVT, however there were clinical improvement in both groups. Complete recanalization with normal augmentation by muscle compression occurred in all Rivaroxaban patients compared to 5% were partially compressible with incomplete recanalization in warfarin group after 6 months of treatment. Conclusion We concluded in patients with unprovoked VTE, rivaroxaban has the potential to reduce both the risk of major bleeding and recurrent VTE compared to warfarin. And there’s no need for adjusting the dose and INR monitoring, and Rivaroxaban has no food nor drug interactions.

Efficacy and safety of direct oral anticoagulants in morbidly obese patients with non-valvular atrial fibrillation: a systematic review and meta-analysis

Introduction Atrial fibrillation (AF) is the most common arrhythmia, with an estimated prevalence between 1–4%. On the other hand, obesity continued to be a prevalent health issue worldwide. Direct oral anticoagulants (DOACs) have been increasingly preferred over warfarin; however, The International Society of Thrombosis and Hemostasis (ISTH) recommended avoiding the use of DOACs in patients with a BMI &gt;40 or weight &gt;120 kg because of limited clinical data in these patients. In this meta-analysis, we aimed to evaluate the efficacy and safety of DOACs in morbidly obese patients with non-valvular AF. Method We performed a comprehensive literature search using multiple databases from database inception through January 2021, for all the studies that evaluated the efficacy and safety of DOACs in morbidly obese patients with non-valvular AF. The primary outcome of interest was stroke or systemic embolism (SSE) rate. The secondary outcome was major bleeding (MB). All meta-analyses were conducted using a random-effect model. Results A total of 10 studies including 89,494 morbidly obese patients (BMI &gt;40 or weight &gt;120 kg) with non-valvular AF on oral anticoagulation therapy (45427 on DOACs vs. 44067 on warfarin) were included in the final analysis. One included study was a randomized controlled trial (RCT), another study was a post hoc analysis of an RCT and the rest were retrospective cohort studies. The mean follow-up period was 1.8 years (range 8 months to 3.1 years). The SSE rate was significantly lower in DOACs group compared to warfarin group (odds ratio (OR): 0.71; 95% confidence interval (CI): 0.62, 0.81; p&lt;0.0001; I2=0%). MB rate was also significantly lower in DOACs group compared to the warfarin group (OR 0.60, 95% CI 0.46–0.78, P&lt;0.0001, I2=86%). Subgroup analysis in the rivaroxaban and apixaban AF cohort showed a statistically significant difference in SSE and MB event rates favoring both over warfarin therapy. Dabigatran showed non-inferiority to warfarin in SSE rate but superiority in the safety outcome. Conclusions Our meta-analysis demonstrated that DOACs are effective and safe when compared to warfarin in morbidly obese patients. However, more large scale randomized clinical trials are needed to further evaluate the efficacy and safety of DOACs compared to warfarin in this cohort of patients. FUNDunding Acknowledgement Type of funding sources: None. Stroke and systemic embolism events Major bleeding events

Vascular Protective Effects of New Oral Anticoagulants in Patients with Atrial Fibrillation

This study was designed to determine the efficacy of a new oral anticoagulant (NOAC) therapy for the prevention of endothelial dysfunction and atherosclerosis progression in patients with atrial fibrillation (AF). Sixty-five AF patients with a CHA2DS2-VASc score ≥2 without previous history of cardiovascular disease were registered and randomly assigned to either an NOAC group (dabigatran or rivaroxaban) or the warfarin group. Reactive hyperemia peripheral arterial tonometry (RH-PAT) measurements reflecting endothelial function were taken using Endo-PAT2000. Carotid intima–media thickness (IMT) was measured at baseline, 12 months, and 24 months, and several biomarkers were also analyzed. For the primary end point, the reactive hyperemia index (RHI) for the NOAC group was 1.5 ± 0.4 and that for the warfarin group was 1.6 ± 0.5. The left and right carotid IMT was 0.7 mm in the NOAC groups and 0.8 mm in the warfarin group. At 12 months, RHI was 1.6 ± 0.3 for the dabigatran group, 1.6 ± 0.5 for the rivaroxaban group, and 1.6 ± 0.3 for the warfarin group. The three groups did not differ statistically with respect to change in left and right carotid IMT at 12 and 24 months, respectively. The biomarkers for endothelial function and atherosclerosis were not significantly different. There was a trend of reduced P-selectin levels in the NOAC group compared to the warfarin group. In patients with AF, there were no significant differences in the prevention of endothelial dysfunction and atherosclerosis progression between the NOAC and warfarin groups.

Correlation between different anticoagulation schemes of pregnant women with mechanical prosthetic heart valves and adverse fetal/neonatal outcomes

Pregnant women with mechanical prosthetic heart valves (MPHV) have adverse effects on the growth and development of the fetus. Data on MPHV pregnant women and their offspring from our hospital from 2014 to 2020 were retrospectively collected. There were 137 pregnancies, 96 in the warfarin group, 28 in the low-molecular-weight heparin (LMWH) group, 13 in the sequential treatment group. There are 27 cases of spontaneous abortion, 3 cases of stillbirth, 56 live births and 51 artificial abortion. The international normalized ratio (INR, P < 0.001), prothrombin time (PT, P = 0.014), activated partial thromboplastin time (APTT, P = 0.035) of the neonates in the warfarin group were increased compared with the other two groups. Multivariate Tobit regression analysis showed that the probability of spontaneous abortion/stillbirth was positively correlated with INR before delivery (OR 1.13, P = 0.009) and valve usage time (OR 1.13, P = 0.009). The probability of malformation was positively correlated with worse heart function level (OR 1.20, P = 0.025) and INR (OR 1.18, P = 0.011) before delivery. The offspring of MPHV pregnant women who continuously take warfarin have poor outcomes and a significantly higher risk of early bleeding. Prenatal consultations for MPHV women should be strengthened to avoid unplanned pregnancy.

Rivaroxaban is Comparable to Warfarin in Prevention of Thromboembolism in Patients with Non-Valvular Atrial Fibrillation with Valvular Heart Disease: A Systematic Review and Meta-analysis

Objectives: While the use of novel oral anticoagulants (NOACs) has been approved in the treatment of non-valvular atrial fibrillation (NVAF), we are lacking studies on individual NOACs in NVAF with valvular heart disease (VHD) including bio-prosthetic valve and valve repair. We aimed to determine the efficacy and safety of rivaroxaban compared to warfarin in prevention of thromboembolism in patients with NVAF with VHD. Methods: We searched PubMed, MEDLINE, and EMBASE including only RCTs and Cohort studies from inception till April 2021. Eligible studies compared rivaroxaban with warfarin in patients with NVAF with VHD. We excluded patients with valvular AF. We used Review Manager (version 5.4, Cochrane Collaboration, Oxford, UK) applying the Mantel-Haenszel test and followed PRISMA guidelines. Risk ratio (RR) and 95% confidence intervals (CIs) were estimated using a random-effects method and heterogeneity using I squared test. Results: We had total of 23136 participants in both groups. Our results showed stroke and systemic thromboembolism in 88 of 4258 (2.06%) patients in the rivaroxaban group compared to 351 of 18878 (1.85%) patients in the warfarin group (RR 0.76; 95% CI, 0.55, 1.06; heterogeneity I2 = 35%, P = 0.10), major bleeding in 247 of 4258 (5.8%) patients in the rivaroxaban group compared to 270 of 18879 (1.4%) patients in the warfarin group (HR 1.68; 95% CI, 0.59, 4.77; heterogeneity I2 = 97%) and intracranial hemorrhage in 24 out of 2583 (0.9%) patients in the rivaroxaban group compared to 35 of 2160 (1.6%) in warfarin group (HR 0.49; 95% CI, 0.16, 1.56; heterogeneity I2 = 70%). Conclusions: Our results show that rivaroxaban is comparable to warfarin in prevention of stroke and systemic thromboembolism in patients with NVAF with VHD. Rivaroxaban is also comparable to warfarin in bleeding risks in these patients.

Rivaroxaban versus warfarin for the management of left ventricle thrombus

Background Rivaroxaban has been recently introduced for the management of non-valvular intra-cardiac thrombosis with variable results. We aimed to compare the results of the off-label use of rivaroxaban versus warfarin in the management of patients with left ventricle (LV) thrombus. This research is a retrospective study conducted on 63 patients who had LV thrombus from January to December 2016. We compared patients treated with warfarin (n=35) to patients who had rivaroxaban (n=28), and study outcomes were time to thrombus resolution, bleeding, stroke, and mortality. Results The median duration of treatment was 9.5 (25th-75th percentiles: 6-32.5) months for rivaroxaban and 14 (3-41) months for warfarin. Thrombus resolution occurred in 24 patients in the warfarin group (68.6%) and 20 patients in the rivaroxaban group (71.4%). The median time to resolution in the warfarin group was 9 (4-20) months and 3 (2-11.5) months in the rivaroxaban group. Thrombus resolution was significantly faster in patients on rivaroxaban (p= 0.019). Predictors of thrombus resolution were thrombus surface area (HR: 1.21; CI 95% (1.0-1.46); p= .048) and the use of rivaroxaban (HR: 1.92; CI 95% (1.01-3.65); p= 0.048). There was no difference in stroke, bleeding, and mortality between both groups. Conclusion Rivaroxaban was as effective and safe as warfarin in managing patients with left ventricle thrombus. Larger randomized clinical trials are recommended to confirm our findings.

UBLED AF study for safety and efficacy between uninterrupted edoxaban, warfarin and rivaroxaban for AF/Fl ablation patients

Funding Acknowledgements Type of funding sources: None. Introduction Catheter ablation in patients with atrial fibrillation (AF)/atrial flutter carries a risk of thromboembolism and major bleeding. Oral anticoagulation is advised for prevention of thromboembolic complications. Purpose In light of recent prospective trial data on the safety and efficacy of uninterrupted edoxaban in patients undergoing AF/flutter ablation, real-world data was aimed to compared. Methods A total of 228 patients who underwent AF/atrial flutter ablation over 14 months at our centre were retrospectively analyzed. All patients received uninterrupted oral anticoagulation for at least 4 weeks prior to ablation and 3 months post-ablation. Both bleeding and thromboembolic events were assessed at 24 hours comparing patients on warfarin, rivaroxaban and edoxaban. Results Mean age of patients were 68.5 +/- 8 years in the warfarin group (N = 86), 63.4 +/- 10.6 years; in the edoxaban group (N = 63) and 62.3 +/- 11.6 years in the rivaroxaban group (N = 79). CHADSVASc scores were 2.43 +/- 1.34, 1.68 +/- 1.34 and 1.64 +/- 1.38 respectively. The mean left atrial sizes were 42.7 +/- 6.8 mm, 42.0 +/- 6 mm and 41.1 +/- 6.5 mm respectively. The study endpoint was death, acute thromboembolism or major bleeding. There was 1 pericardial effusion (1.2%) in the warfarin group, 1 pericardial effusion and 1 transient ischaemic attack (2.5%) in the rivaroxaban group and 1 pericardial effusion needing drainage (1.6%) in the edoxaban group. There were no significant differences in the study endpoints between groups. Conclusion This real-world study demonstrated no significant difference in safety and efficacy between uninterrupted edoxaban, warfarin and rivaroxaban in patients undergoing AF/flutter ablation.