Direct Oral Anticoagulants for Rheumatic Heart Disease-Associated Atrial Fibrillation Post-Bioprosthetic Mitral Valve Replacement.

BACKGROUND: The efficacy of direct oral anticoagulants (DOACs) in preventing ischemic and thromboembolic events may be suboptimal in atrial fibrillation (AF) patients with rheumatic mitral stenosis. However, their safety and effectiveness after mitral valve replacement (MVR) using bioprosthetic valves is unclear. OBJECTIVES: This study sought to evaluate the safety and effectiveness of DOACs vs warfarin among patients with rheumatic heart disease (RHD)-associated AF after bioprosthetic MVR. METHODS: We performed an observational analysis identifying patients with RHD and AF who underwent bioprosthetic MVR. Primary effectiveness and safety outcomes were ischemic events and major bleeding, respectively. Secondary outcomes included all-cause mortality, cardiac thrombosis, myocardial infarction, and all-cause hospitalization. Propensity score matching was performed to account for the differences in baseline characteristics and comorbidities. RESULTS: A total of 3,950 patients were identified; 76% were on warfarin and 24% on DOAC post-MVR. The DOAC group had a higher burden of baseline comorbidities and prior cardiovascular procedures compared with the warfarin group. The propensity score matching balanced baseline characteristics in 1,832 patients (916 in each group), with a mean age of 69 years. At the 5-year follow-up, DOACs were associated with a lower incidence of major bleeding compared with warfarin (HR: 0.76; 95% CI: 0.62-0.94), with no significant difference in ischemic events, mortality, cardiac thrombosis, myocardial infarction, or hospitalization. CONCLUSIONS: Among patients with RHD-associated AF patients post-bioprosthetic MVR, DOACs are associated with lower major bleeding and comparable effectiveness, indicating a potential alternative to warfarin. Further randomized controlled trials are warranted to validate these findings in this population.

Chronic Anticoagulation in Patients Who Have Atrial Fibrillation Undergoing Outpatient Total Knee Arthroplasty: A Retrospective Matched Cohort Study.

BACKGROUND: Patients who have atrial fibrillation frequently require long-term anticoagulation with warfarin or a direct-acting oral anticoagulant (DOAC), such as apixaban or rivaroxaban, to avoid vascular complications. However, the impact of anticoagulant use on postoperative complications following total knee arthroplasty (TKA) in an outpatient setting has not been thoroughly elucidated. The purpose of this study was to examine the impact of anticoagulant use on early postoperative complications among atrial fibrillation patients undergoing outpatient TKA. METHODS: An insurance claims database was queried to identify all patients who underwent outpatient TKA between January 2010 and April 2022. There were two cohorts of patients, with associated 1:1 matched controls, who had atrial fibrillation and filled a prescription of either warfarin (N = 4,396) or DOAC (N = 5,383) for at least 30 days. The mean age was 70 years (range, 51 to 84 years) and 47.9% were women in the warfarin cohort, while the mean age was 70 years and 49.2% were women in the DOAC cohort. Postoperative 30-day medical and 90-day surgical complications were subsequently compared. RESULTS: Patients on warfarin had a higher incidence of pulmonary embolism (1.1 versus 0.2%, P < 0.001) and a lower incidence of TKA revision (0.1 versus 0.4%, P = 0.003) than matched controls. Similarly, patients on DOACs exhibited a higher incidence of pneumonia (1.4 versus 0.6%, P < 0.001) and myocardial infarction (3.2 versus 1.5%, P < 0.001) and a lower incidence of wound dehiscence (0.1 versus 0.5%, P < 0.001), joint infection (0.4 versus 0.9%, P = 0.002), and TKA revision (0.1 versus 0.4%, P = 0.002) than matched controls. CONCLUSIONS: Atrial fibrillation patients on long-term anticoagulants undergoing outpatient TKA experience higher rates of medical complications and lower rates of surgical complications than matched controls. Thus, patients on long-term anticoagulants may be considered for outpatient TKA, but should be counseled appropriately on associated medical risks.

Rates and risk factors of bleeding after gastric endoscopic submucosal dissection with continuous warfarin or 1-day withdrawal of direct oral anticoagulants.

BACKGROUND AND AIM: The 2017 Japanese guidelines recommend continuing warfarin therapy during the perioperative period or discontinuing direct oral anticoagulants (DOACs) only on the day of endoscopic submucosal dissection for early gastric cancer. However, their safety has not been sufficiently explored. This study aimed to validate this management method. METHODS: This retrospective, multicenter study analyzed the characteristics and outcomes of patients who underwent gastric endoscopic submucosal dissection between July 2017 and June 2019. The patients were categorized according to the use of warfarin or DOACs. RESULTS: Among the 62 eligible patients, 53 (85%) were male (median age, 76 years). Warfarin was used in 10 patients (16%) and DOACs in 52 patients (84%). Fourteen patients taking DOACs (27%) used concomitant antiplatelet agents, with seven patients (13%) continuing treatment at the time of the endoscopic procedure. No postprocedural bleeding occurred in patients receiving warfarin (0%), whereas 10 cases (19%) of bleeding occurred in patients receiving DOACs: rivaroxaban, 0% (0/22); dabigatran, 0% (0/2); edoxaban, 43% (6/14); and apixaban, 29% (4/14). The type of anticoagulant (P < 0.01) and continuation of antiplatelet therapy (P = 0.02) were risk factors for postprocedural bleeding in patients receiving DOACs. Intraprocedural bleeding requiring transfusion or symptomatic thromboembolic events were not reported. CONCLUSIONS: Continuous warfarin therapy is preferred. DOAC withdrawal 1 day before a procedure is associated with a high bleeding rate, which may differ for different types of anticoagulants. The continuation of antiplatelet medications in patients receiving DOACs carries a high risk of bleeding and is a future challenge.

Exploring bleeding in oral anticoagulant users: assessing incidence by indications and risk factors in the entire nationwide cohort.

Background: Oral anticoagulants (OACs) are essential for the prevention and treatment of thromboembolic disorders, but bleeding, a major complication, can have a fatal impact on the patient's treatment. Objectives: We aimed to estimate the nationwide, real-world incidence rate of bleeding in patients taking OACs and confirm the incidence by indications and risk factors. Methods: This cross-sectional study identified OAC users from April 1 to December 31, in both 2019 and 2020, using the HIRA-NPS database. The primary outcome variables were the incidence rate of major bleeding events during OAC treatment and within 30 days of treatment discontinuation. We estimated the adjusted incidence rate ratio (aIRR) in subpopulations. Results: Among 18,822 OAC users, the incidence rate of major bleeding was 27.9 (95% CI: 24.6-31.5) per 1,000 person-years. The incidence rate of major bleeding was higher in patients with a bleeding history, with an aIRR of 11.51; those at high bleeding risk (HAS-BLED score ≥3), with an aIRR of 1.51; those with high CCI scores ≥3, with an aIRR of 1.88; and those with liver disease, with an aIRR of 1.41. For indications, compared to patients with nonvalvular atrial fibrillation (NVAF), the aIRR of major bleeding was significantly higher at an aIRR of 2.35 in patients undergoing VTE treatment. Patients with ischemic stroke showed a higher incidence of major bleeding with an aIRR of 2.13 than NVAF patients. The aIRR of major bleeding in the oral anticoagulant group, compared to the matched control group, was 2.25 (95% CI: 1.93-2.63). Conclusion: These findings may be useful for implementing strategies to improve the evaluation and management of anticoagulation-related bleeding.

Modern psychometric evaluation of Thai WHOQOL-BREF and its shorter versions in patients undergoing warfarin in Thailand: Rasch analysis.

Rasch analysis was employed to investigate the psychometric properties of the World Health Organization Quality of Life-BREF (WHOQOL-BREF) and its shorter versions (EUROHIS-QOL-8 and WHOQOL-5) within the context of patients undergoing warfarin in Thailand. A group of 260 patients were recruited from three public hospitals and tasked with completing the WHOQOL-BREF questionnaire. Rasch analysis showed that the WHOQOL-BREF, structured into four-domain subtests, achieved a commendable fit to the Rasch model (χ2[16] = 12.26, p = 0.73), met the criterion of unidimensionality (7.31% significant t-tests; lower bound confidence interval, 4.66), and demonstrated satisfactory reliability (PSI = 0.87). The adoption of a subtest approach facilitated an acceptable fit to the Rasch model for each domain of the WHOQOL-BREF, except for the social domain. However, the presence of local dependency of the three-item social domain was detected, so the reliability was not reported. The WHOQOL-5 proved to be unidimensional, fitting the Rasch model acceptably, and had satisfactory reliability. Conversely, the EUROHIS-QOL-8 presented local dependency; thus, reliability was not reported. Consequently, the WHOQOL-BREF in its four-domain subtests is recommended for pre- and post-HRQoL measurements, whereas the WHOQOL-5 can effectively measure HRQoL levels in between-group analyses.

Frontoparietal intraparenchymal hemorrhage secondary to anticoagulation.

The authors present the case of a patient experiencing frontoparietal intraparenchymal hemorrhage. With a history of a mechanical heart valve due to rheumatic disease, the patient was on warfarin and experienced a warfarin-associated bleed. The new 2002 guidelines for the management of intracerebral hemorrhage are discussed in the context of this case.

Risk of spontaneous intracerebral hemorrhage associated with NOACs compared with aspirin and warfarin: A long-term single hospital follow-up study.

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) are currently the mainstay treatment for preventing thrombosis-induced ischemic stroke in patients with atrial fibrillation (AF), deep vein thrombosis (DVT), or previous infarction. However, such management may potentially induce antithrombotic-associated intracranial hemorrhage, leading to significantly adverse clinical outcomes. To investigate the risk of spontaneous intracranial hemorrhage (sICH) in patients under therapeutic anticoagulation. METHODS: This retrospective cohort study used a database established by Kaohsiung Veterans General Hospital to estimate the risk of first onset sICH in patients with AF, DVT or previous stroke who were 18 years old or older, and who had been on at least three months continuous long-term treatment with the oral anticoagulants aspirin, warfarin, or NOACs. In addition, we used propensity-score matching to minimize bias and Cox proportional hazards ratio to compare the risk of sICH among patients prescribed these anticoagulants. RESULTS: We analyzed the data of 546 patients (182 aspirin users, 182 warfarin users, and 182 NOAC users). 180 (20 taking aspirin, 74 warfarin, and 86 NOACs) developed new onset sICH before seven years. No new onset cases were found after 7 years. Importantly, those taking NOACs were found to be at a higher risk of early onset hemorrhage (47.80 %) compared to the groups taking aspirin (11.10 %) and warfarin (47.80 %) with a median time-to-occurrence being 2.50, 4.00, and 4.40 years, respectively. CONCLUSIONS: Though NOACs prevented ischemic stroke, they were used with a higher risk of early onset spontaneous ICH at our large medical center.

Ovarian Ectopic Pregnancy in a Female With Mitral Valve Repair and Mitral Stenosis: A Case Report on a Rare Type of Ectopic Pregnancy.

Ovarian ectopic pregnancy (OEP) occurs in cases where the fertilized egg is implanted outside the uterus in either of the ovaries. Assisted reproductive technologies and intrauterine device failure are high-risk factors associated with ovarian ectopic pregnancy. Pregnancies categorized under OEP have a higher risk of serious morbidities to maternal health. Clinical presentations of OEP are usually noted as abdominal pain and vaginal bleeding. Transvaginal ultrasound is considered the preferred primary modality for the diagnosis of OEC. It can be life threatening, especially in patients with mitral valve replacement (MVR) or heart diseases like rheumatic heart disease, majorly due to anticoagulant therapy. Pregnancy in MVR-mitral stenosis patients has been reported to have an increased risk of obstetric hemorrhage, miscarriage, and associated complications during delivery. Management of OEP depends on the patient's physical and clinical condition, with a primary focus on preserving the affected ovary function. This is a case of a 35-year-old pregnant female with a history of MVR presented with per vaginal bleeding and ruptured ectopic pregnancy. Radio imaging showed the product of conception attached to the right ovarian cyst. The patient was counseled for exploratory laparotomy and subsequently had right ovarian cystectomy alone with bilateral tubal ligation by modified Pomeroy's method.

Vkorc1 polymorphisms of the Norway rats in China: Implications for rodent management and evolutionary origin of anticoagulant resistance mutations.

The extensive utilization of second-generation anticoagulant rodenticides (SGARs) has raised concerns regarding non-target animal safety and environmental contamination. It is essential to assess the anticoagulant resistance level in rodent populations and prioritize the use of relative low toxic first-generation anticoagulant rodenticides (FGARs) in susceptible rodent populations. Mutations in the vitamin K epoxide reductase complex subunit 1 (Vkorc1) gene confer anticoagulant resistance in Norway rats. However, the Vkorc1 polymorphisms remain unclear in most Norway rat populations in China although anticoagulant rodenticides have been widely used in China since the 1980s. Analysis of the Vkorc1 polymorphisms in 489 rats across China, combined with in silico binding affinity analysis, revealed three potential resistance mutations A26T, C96Y, and A140T at three distinct locations. In the remaining locations, Vkorc1 resistance mutations were absent, indicating that the FGARs could be effective in these areas. Additional evolutionary analysis of different Vkorc1 mutations suggested that the three missense mutations identified in China might have evolved independently as de novo mutations, and the resistance mutations in Europe are unlikely to be pre-existing variations in China. Further analysis of Vkorc1 haplotypes among European resistant rat populations is essential for understanding the origin of these resistance mutations. These findings emphasize the importance of customizing rodent control strategies in China based on regional resistance levels and gaining insights into the origins of Vkorc1 mutations for more effective rodent management strategies.

Accuracy of an internationally validated genetic-guided warfarin dosing algorithm compared to a clinical algorithm in an Arab population.

PURPOSE: To identify the impact of CYP2C9*2, *3, VKORC1-1639 G>A and CYP4F2*3 on warfarin dose in an Arab population. To compare the accuracy of a clinical warfarin dosing (CWD) versus genetic warfarin dosing algorithms (GWD) during warfarin initiation. METHODS: A cohort of Arab patients newly starting on warfarin had their dose calculated using CWD published in www.warfarindosing.org and were followed for 1 month. Each patient provided a saliva sample. DNA was extracted, purified and genotyped for VKORC-1639 G>A, CYP2C9*2, CYP2C9*3 and CYP4F2*3. After reaching warfarin maintenance dose, the dose was recalculated using the GWD and median absolute error (MAE) and the percentage of warfarin doses within 20% of the actual dose were calculated and compared for the two algorithms. RESULTS: The study enrolled 130 patients from 12 Arabian countries. Compared to those with wild type, carriers of reduced function alleles in CYP2C9 required significantly lower median (IQR) warfarin weekly dose [24.5 (15.3) vs. 35 (29.8) mg/week, p=0.006]. With regards to VKORC, patients with AA genotype had a significantly lower median (IQR) weekly warfarin dose compared to AG and GG [21(10.5) vs 29.4 (21), p<0.001 for AA vs AG, p<0.001 for AA vs GG]. The MAE (IQR) for the weekly dose of the GWD was significantly lower compared to CWD [8.1 (10.5) vs 12.4 (12.6) (p<0.001)]. CONCLUSION: CYP2C9 and VKORC1 variants are important determinants of warfarin dose in the Arab population. The use of the genetic and clinical factors led to better warfarin dose estimation when compared to clinical factors alone.