Warfarin Use Research Articles

Evaluation of modified fixed dose four-factor prothrombin complex concentrate for warfarin reversal.

Non-activated four-factor prothrombin complex concentrate (4F-PCC) has emerged as the preferred reversal strategy for patients on warfarin with life-threatening bleeding. Current dosing recommendations for 4F-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 4F-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 4F-PCC, a time analysis, incidence of concomitant vitamin K administration, and incidence of thrombosis within seven days of 4F-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 4F-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 4F-PCC was effective in reversing INR to less than two in most patients regardless of reversal indication with minimal thrombotic risks.

Complications of the use of Warfarin during pregnancy and Fetal Warfarin Syndrome: Scientific Review

Complications of the use of Warfarin during pregnancy and Fetal Warfarin Syndrome: Scientific Review

Balancing fracture risk versus risk of mortality before fracture among women aged 80 years or older.

Most fractures occur in women aged ≥80 years but competing mortality unrelated to fracture may limit the benefit of osteoporosis drug therapy for some women in late life. Our primary aim was to develop separate prediction models for non-spine fracture (NSF) and mortality before fracture to identify subsets of women with varying fracture versus mortality risks. Separate prediction models were developed for NSF and mortality before NSF for 4895 women aged ≥80 years enrolled in the Study of Osteoporotic Fractures (SOF) or the Health Aging and Body Composition (HABC) study. Proportional hazards models modified to account for competing mortality were used to identify candidate risk factors for each outcome. Predictors associated with NSF or mortality (p < 0.2) were included in separate competing risk models to estimate the cumulative incidence of NSF and mortality before NSF during 5 years of follow-up. This process was repeated to develop separate prediction models for hip fracture and mortality before hip fracture. Significant predictors of NSF (race, total hip BMD, grip strength, prior fracture, falls, and use of selective serotonin reuptake inhibitors, benzodiazepines, or oral/transdermal estrogen) differed from predictors of mortality before NSF (age, walking speed, multimorbidity, weight change, shrinking, smoking, self-rated health, dementia, and use of warfarin). Within nine subsets of women defined by tertiles of risk, 5-year outcomes varied from 28% NSF and 8% mortality in the high-risk NSF/low-risk mortality subset, to 9% NSF and 22% mortality in the low-risk NSF/high-risk mortality subset. Similar results were seen for predictors of hip fracture and mortality before hip fracture. Considerable variation in 5-year competing mortality risk is present among women in late life with similar 5-year NSF risk. Both fracture risk and life expectancy should inform shared clinical decision-making regarding initiation or continuation of osteoporosis drug therapy for women aged ≥80 years.

Oral prednisolone and warfarin and risk of oesophageal cancer: A case-control study.

A recent epidemiological study systematically screened 250 prescription medications for associations with oesophageal cancer risk, using Scottish data, and identified an increased risk with use of prednisolone and warfarin. We investigated whether oral prednisolone or warfarin use was associated with increased oesophageal cancer risk. A case-control study was conducted within the Clinical Practice Research Datalink. In the primary analysis oesophageal cancer cases were identified from linked cancer registry records. Up to 5 cancer-free controls were matched to each case (based upon sex, birth year, GP practice and year of GP registration). Prednisolone and warfarin medications were identified from prescribing records. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression after adjusting for covariates including demographics, comorbidities and medication use. There were 4552 oesophageal cancer cases and 22,601 matched control participants. Overall, there was no evidence of an increased risk of oesophageal cancer with oral prednisolone use (unadjusted OR=1.16 95% CI 1.06, 1.27 and adjusted OR=0.99 95% CI 0.89, 1.11) or warfarin use (unadjusted OR=1.12 95% CI 0.99, 1.28 and adjusted OR=1.08 95% CI 0.92, 1.27). In this large population-based study, oral prednisolone and warfarin were not associated with oesophageal cancer risk.

Gender Differences in Patients with Atrial Fibrillation Receiving Oral Anticoagulants.

Gender is a well-recognized risk factor in atrial fibrillation (AF)-related ischemic stroke. The association of gender with the use of oral anticoagulants (OACs) and prognosis remains unknown. The National Health Insurance Research Database in Taiwan identified 203,775 patients with AF aged 20 years from 2012 to 2018, with 55.4% of males. Our main study cohort included 67,426 patients using OACs. The study endpoints include death, ischemic stroke, intracranial hemorrhage, major bleeding, and composite adverse events. Significant differences were found in baseline characteristics between sexes. Female patients with AF were older and had higher -VASc and HAS-BLED scores. Non-vitamin K antagonist oral anticoagulant (NOAC) use was more prominent in females while the use of warfarin was similar in both sexes. The distribution of baseline characteristics between the warfarin and NOAC groups in both sexes was much alike. Among the whole study cohort, NOAC was associated with a decreased risk of clinical endpoints compared to warfarin, which remained the same in subgroup analyses of both sexes. Additionally, a greater risk reduction of ischemic stroke with NOAC was observed in female patients compared to male patients (adjusted hazard ratio: 0.517 in males, 0.425 in females, interaction p = 0.040). This nationwide cohort demonstrated the differences between male and female patients with AF, including baseline characteristics, risk profiles, and medication use. Despite great differences in baseline demographic data, NOAC was associated with better clinical outcomes compared to warfarin in both sexes, and females benefited more than males in preventing ischemic stroke using NOACs.

Fetal Warfarin Syndrome - A Case Report

Fetal warfarin syndrome (FWS) or warfarin embryopathy also known as “Di Sala syndrome” is a rare fetal anomaly which occurs as a result of fetal exposure to warfarin during the early stages of pregnancy. FWS is characterised by nasal hypoplasia and skeletal abnormalities, including short limbs and digits and stippled epiphyses. Here we present a case of foetal embryopathy due to warfarin use in a female with an unplanned pregnancy while taking warfarin for cerebral venous thrombosis. The case was reported in Adverse Drug Reaction (ADR) Monitoring centre in August 2023. The purpose of this case report is to caution all the clinicians particularly obstetricians regarding the fetal abnormalities of warfarin. If the mother had history of warfarin usage, paediatricians should also be vigilant regarding the possibility of congenital warfarin syndrome in the newborn.&#x0D; Warfarin is an oral anticoagulant drug that decreases the production of clotting factors (II, VII, IX, X) which are vitamin K-dependent. Warfarin is used in the treatment of patients with thromboembolic disorders and in patients who are predisposed to the development of thrombus. Especially those people with prosthetic heart valves, those who have had ischemic stroke and atrial fibrillation. Warfarin is a teratogen which can cross the placental barrier and cause harm to the developing foetus.[1] Warfarin causes inhibition of clotting factors leading to internal bleeding of the fetus, while inhibition of osteocalcin retards bone growth. In addition to birth defects, warfarin can induce spontaneous abortion, premature delivery, neonatal death and even congenital anomalies known as fetal warfarin syndrome.[2] The risk of teratogenicity is not predictable with any dose of warfarin. The first case of embryopathy due to warfarin was reported by Di Sala in 1966 hence, it is also known as Di Sala syndrome.[3,4] Warfarin leads to embryopathy which is characterized by the abnormalities of cartilages and bones known as chondrodysplasia punctata.[5] Almost 6% of babies born to mothers treated with warfarin during the first trimester have a pattern of congenital anomalies like nasal hypoplasia and stippling of vertebrae or bony epiphyses.[6] So, warfarin is contraindicated during pregnancy.&#x0D; Here we present a case of foetal embryopathy due to warfarin use in a female with an unplanned pregnancy while taking warfarin for cerebral venous thrombosis. This form of stroke is relatively rare and underdiagnosed which accounts for 0.5%-1% of all strokes mostly occurring in young adults, especially in women. Pregnancy, use of oral contraceptive pills (OCPs), puerperium, malignancies and other conditions with hypercoagulable states have been recognised as predisposing risk factors.[7] The conventional therapy for venous thromboembolism includes treatment with parenteral low-molecular-weight heparin (LMWH) and the vitamin K antagonist warfarin.[7]

Major bleeding in patients with atrial fibrillation treated with apixaban versus warfarin in combination with amiodarone: nationwide cohort study

BackgroundAmiodarone is an established treatment for atrial fibrillation (AF) but might interfere with the metabolism of apixaban or warfarin. Therefore, the aim was to investigate the occurrence of major bleeding...

Optimizing Warfarin use in Egyptian patients with Autoimmune Diseases – Genetic and Clinical Related Factors

Introduction: Over the last Century, Thousands of studies were conducted to highlight the factors affecting warfarin efficacy and toxicity. Many of these studies had major limitations because they focused only on one or a few factors. Objectives: to determine the effect of 14 different clinical and genetic factors on the clinical outcomes (efficacy and toxicity) of warfarin in Egyptian patients with autoimmune diseases. The secondary objective was detecting the association between genetic polymorphisms of VKORC1 (rs 9923231) and systemic lupus erythematosus (SLE) susceptibility in the Egyptian population. Methods: after signing a consent form, 150 patients were included in the study from Kasr Aleiny Hospital, Cairo University. All medical records were reviewed to extract the effect of age, sex, diagnoses, genotypes, warfarin-drug interactions, and all patients' comorbidities on warfarin's efficacy and toxicity. The average warfarin doses, INR, (No. of times)/total times of INR within the therapeutic range, differences between the maximum and minimum INR values, the addition of enoxaparin and discontinuing warfarin and shifting to Rivaroxaban, and bleeding episodes were determined. Results: all the studied factors had clinical and statistical significance on the clinical outcomes. The T allele was associated with treatment failure and a shift to rivaroxaban, a higher risk of bleeding and SLE. Conclusions: Awareness of the effect of the factors addressed in this study is mandatory for the assessment of warfarin efficacy and toxicity for each patient. Further studies are essential in other specialties because different warfarin-drug interactions may be detected, with other comorbidities and on different genes.

Abstract TMP51: Clinical Factors Associated With Enlarged Perivascular Spaces in a US Population of Caucasian Descent

Introduction: Enlarged Perivascular Spaces (EPVS), characterized by distinct cerebrospinal fluid-filled structures surrounding intracranial vessels, have garnered growing attention concerning brain aging and cerebrovascular disorders. This study investigates the associations between EPVS and a spectrum of clinical factors and conditions in a large community-based sample in the northeastern United States. Method: This research was conducted on a subset of the Geisinger DiscovEHR Initiative Cohort. The total numbers of EPVS were categorized into five grades (0-4) in centrum semiovale and basal ganglia regions. A comparison was established between patients with EPVS and a propensity-score-matched cohort devoid of EPVS. Matching factors included age, gender, body mass index, and hypertension. Results: Among 3054 randomly selected participants (mean age 67.5 years, 57.4% women), 1465 (47.9%, mean age 69.6 years, 58% women) exhibited EPVS in their brain imaging. The presence of EPVS was linked to cerebral aneurysm (OR, 2.40; 95% CI, 1.5-4.0), heart failure (OR, 2.0; 95% CI, 1.5-2.8), peripheral vascular disease (OR, 1.5; 95% CI, 1.1-2.15), Parkinson's Disease (OR, 1.9; 95% CI, 1.2-3.1), history of ischemic stroke (OR, 1.18; 95% CI, 1.0-1.4), non-central nervous system malignancies (OR, 1.4; 95% CI, 1.1-2.0), smoking (OR, 1.3; 95% CI, 1.0-1.6), and warfarin use (OR, 0.76; 95% CI, 0.6-0.9). Higher scales of EPVS were notably associated with obstructive sleep apnea (OR, 1.9; 95% CI, 1.0-3.8) and hypertension (OR, 3.1; 95% CI, 1.1-9.9). Conclusion: EPVS presence and severity may be associated with several vascular risk factors, providing potential avenues for risk assessment and further research.

Direct oral anticoagulants compared to warfarin in long-term management of cerebral venous thrombosis: A comprehensive meta-analysis.

We compared the safety and efficacy of direct oral anticoagulants (DOACs) with those of warfarin in the long-term (≥6 months) treatment of cerebral venous thrombosis (CVT). We searched electronic databases up to November 2023 to compare the use of DOACs and warfarin in CVT management. Modified Rankin scores (mRS), new intracranial hemorrhage, all-cause mortality, recurrence and nonrecanalisation events were used to assess outcome. RevMan v5.4 software and the Cochran-Mantel-Haenszel method were utilized to analyse data. A total of 25 studies involving 2301 patients were identified as having treated CVT with either DOACs or warfarin. Good long-term mRS scores 0-2 (risk ratio [RR] = 1.01, 95% CI = 0.98-1.03; p = 0.61), new intracranial hemorrhage (RR = 1.00, 95% CI = 0.48-2.08; p = 0.99), all-cause mortality (RR = 1.00, 95% CI = 0.50-1.98; p = 0.99), nonrecanalisation (RR = 0.95, 95% CI = 0.77-1.18; p = 0.65) and recurrence venous thrombosis events (RR = 0.63, 95% CI = 0.33-1.22; p = 0.17) were similar between the two treatment arms. Subgroup analysis found recurrence of venous thrombosis was lower in the rivaroxaban group compared to warfarin (2.2% vs. 8.5%, RR = 0.33, 95% CI = 0.11-0.98; p = 0.05). DOACs and warfarin provide comparable long-term safety and efficacy profiles. DOACs may be preferred over warfarin due to their ease of clinical management.

Abstract WMP10: Carotid Floating Thrombus; Medical Management and Outcomes

Background: Carotid free-floating-thrombus(CFT)is a rare cause of stroke describing an intraluminal thrombus that is loosely associated with the arterial wall and manifesting as a filling defect fully surrounded by contrast. Unfortunately, there is no clear consensus among experts on the ideal treatment for CFT. Methods: Retrospective analysis of acute ischemic stroke(AIS)patients diagnosed with internal carotid CFT on CTA between January2015-March2023.We aimed to compare two treatment regimens: antiplatelet(APT) and anticoagulation(ACT) in the treatment of CFT. APT regimens included the use of dual or single APT (aspirin, clopidogrel and ticagrelor) and ACT regimens included the use of direct oral anticoagulants, warfarin, heparin or low molecular weight heparin+/-aspirin. Patients that underwent thrombectomy were excluded. Results: During study time there were 8252 AIS patients, of which 137(1.6%) patients were diagnosed with CFT. Sixty-six patients were included in our analysis. Patients assigned to APT were older (60.4years + 12.8;p&lt;0.01) (Table 1) .Other demographic variables were similar between groups. Complete CFT resolution by repeat imaging was comparable between groups at 30 days (58.8vs31.6%;p=0.1) and at latest follow-up (70.8vs50%;p=0.1) on ACT vs APT, respectively. There were similar rates of any ICH (13.5vs27.6%;p=0.5), PH1/2, independence at discharge and similar hospital length of stay between APT and ACT groups, respectively ( Table 1 ). Patients assigned to APT were more likely to be discharged on their assigned treatment compared to those assigned to ACT (86.5vs55.2%;p&lt;0.001).The rate of recurrent AIS was comparable among APT and ACT at 30 days (0vs3.4%;p=0.1,respectively).Sensitivity analysis comparing DAPT to exclusive ACT lead to similar results. Conclusion: Our study showed comparable efficacy and safety outcomes in CFT patients who were exclusively managed with APT vs ACT. Larger prospective studies are needed.

Clinical outcomes and anticoagulation therapy in elderly non-valvular atrial fibrillation and heart failure patients.

Atrial fibrillation (AF) and heart failure (HF) often coexist. Older age is strongly associated with stroke, HF, and mortality. The association between coexistence of HF and a risk of clinical outcomes and the effectiveness of anticoagulation therapy including direct oral anticoagulants (DOACs) in elderly patients with AF and HF have not been investigated. We aimed to evaluate 2years of outcomes and to elucidate the efficacy of DOACs or warfarin in elderly AF patients in the All Nippon AF In the Elderly (ANAFIE) Registry with and without a history of HF. The ANAFIE Registry is a multicentre, prospective observational study following elderly non-valvular AF patients aged ≥75years for 2years. Hazard ratios (HRs) were calculated based on the presence or absence of an HF diagnosis and DOAC or warfarin use at enrolment. Among 32275 eligible patients, 12116 (37.5%) had been diagnosed with HF. Patients with HF had significantly higher rates of HF hospitalization or cardiovascular death (HR 1.94, P<0.001), cardiovascular events (HR 1.59, P<0.001), cardiovascular death (HR 1.49, P<0.001), all-cause death (HR 1.32, P<0.001), and net clinical outcome including stroke/systemic embolism, major bleeding, and all-cause death (HR 1.23, P<0.001), compared with those without HF; however, HRs for stroke/systemic embolism (HR 0.96, P=0.56) and major bleeding (HR 1.14, P=0.13) were similar. DOAC use was associated with a low risk of stroke/systemic embolism (HR 0.86, P=0.19 in HF; HR 0.79, P=0.016 in non-HF; P for interaction=0.56), major bleeding (HR 0.71, P=0.008 in HF; HR 0.75, P=0.016 in non-HF; P for interaction=0.74), HF hospitalization or cardiovascular death (HR 0.81, P<0.001 in HF; HR 0.78, P<0.001 in non-HF; P for interaction=0.26), cardiovascular events (HR 0.83, P<0.001 in HF; HR 0.82, P=0.001 in non-HF; P for interaction=0.65), cardiovascular death (HR 0.84, P=0.12 in HF; HR 0.75, P=0.035 in non-HF; P for interaction=0.18), all-cause death (HR 0.89, P=0.082 in HF; HR 0.80, P=0.001 in non-HF; P for interaction=0.091), and net clinical outcome (HR 0.88, P=0.019 in HF; HR 0.81, P<0.001 in non-HF; P for interaction=0.21) compared with warfarin, irrespective of the presence or absence of HF. Analysis using the propensity score matching method showed similar associations. Non-valvular AF patients aged ≥75years with a history of HF had higher risks of cardiovascular events and mortality. DOACs were favourable to warfarin regardless of the coexistence of HF. These results might encourage the use of DOACs in elderly patients with non-valvular AF with or without HF.

Prevalence and associated factors of cerebral microbleeds in a rural population of the United States

ObjectiveCerebral microbleeds (CMBs) can carry an advanced risk for the development and burden of cerebrovascular and cognitive disorders. Large-scale population-based studies are required to identify the at-risk population. MethodTen percent (N = 3,056) of the Geisinger DiscovEHR Initiative Cohort participants who had brain magnetic resonance imaging (MRI) for any indication were randomly selected. Patients with CMBs were compared to an age-, gender-, body mass index-, and hypertension-matched cohort of patients without CMB. The prevalence of comorbidities and use of anticoagulation therapy was investigated in association with CMB presence (binary logistic regression), quantity (ordinal regression), and topography (multinomial regression). ResultsAmong 3,056 selected participants, 477 (15.6 %) had CMBs in their MRI. Patients with CMBs were older and were more prevalently hypertensive, with ischemic stroke, arrhythmia, dyslipidemia, coronary artery disease, and the use of warfarin. After propensity-score matching, 477 patients with CMBs and 974 without were included for further analyses. Predictors of ≥5 CMBs were ischemic stroke (OR, 1.6; 95 % CI, 1.2 -2.0), peripheral vascular disease (OR, 1.6; 95 % CI, 1.1–2.3), and thrombocytopenia (OR, 1.9; 95 % CI, 1.2–2.9). Ischemic stroke was associated with strictly lobar CMBs more strongly than deep/infra-tentorial CMBs (OR, 2.1; 95 % CI, 1.5–3.1; vs. OR, 1.4; CI, 1.1–1.8). ConclusionsCMBs were prevalent in our white population. Old age, hypertension, anticoagulant treatment, thrombocytopenia, and a history of vascular diseases including stroke, were associated with CMBs.

OUTCOMES OF WARFARIN THERAPY FOR SECONDARY PREVENTION OF ISCHEMIC STROKE: A RETROSPECTIVE, FOLLOW-UP STUDY

Aim: Anticoagulant prophylaxis is recommended because cardioembolic ischemic stroke is associated with worse functional outcomes, increased recurrence rates, and higher mortality. This study aimed to investigate the rates of recurrent ischemic attacks and bleeding complications in patients receiving warfarin following ischemic stroke. Method: In this retrospective analysis, a total of 181 individuals who were initiated on warfarin therapy following an ischemic stroke were included in the study. These patients were subsequently monitored for a duration spanning from 1 month to as long as 16 years. The acute ischemic stroke diagnosis was established using the Trial of Org 10172 in Acute Stroke Treatment classification criteria. Patient follow-up periods, international normalized ratio (INR) levels, ischemic events, and bleeding were recorded and evaluated. Results: In the patient cohort, 97 (53.6%) were women and 84 (46.4%) were men. The recurrent ischemic stroke rate was 7.2%, major bleeding rate was 3.3%, and minor bleeding rate was 12.7%. While the average INR value during recurrent ischemic stroke was 1.69±0.31, the average INR value during bleeding complications was observed to be 3.15±1.38. The rate of minor bleeding was related to duration of warfarin use and non-valvular atrial fibrillation. Conclusion: Our results show that long-term warfarin use and non-valvular atrial fibrillation are risk factors for bleeding.

Effectiveness and Safety of the Coadministration of Rifampin and Warfarin versus Direct Oral Anticoagulants: A Cohort Study.

Pharmacokinetic studies have shown that rifampin reduces the levels of oral anticoagulants during the initiation of coadministration, raising concerns about an increased thrombotic risk, but there are limited comparative clinical outcomes between rifampin and warfarin compared with direct oral anticoagulants (DOACs). This study aimed to evaluate the effectiveness and safety of concurrent use of rifampin and warfarin versus DOACs, with assessments of outcome-associated factors and oral anticoagulant (OAC) management quality. A total of 142 patients given rifampin plus warfarin (n = 56) or DOACs (n = 86) for over 7 days were included, and their clinical data and outcomes were compared. The median Charlson Comorbidity Index and HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile INR, elderly, drugs/alcohol concomitantly) score of the two groups were 2 and 3, respectively. The incidence rate of composite ischemic or thromboembolic events was 2.16 and 1.44 per 10,000 patient-days in the warfarin and DOAC groups, respectively, with an adjusted hazard ratio (HR) of 0.41 (95% confidence interval [CI] 0.02-7.34). The incidence rate of composite major bleeding or clinically relevant nonmajor bleeding events was 1.58 and 1.52 per 10,000 patient-days in the warfarin and DOAC groups, respectively, with an adjusted HR of 1.12 (95% CI 0.32-4.45). The risk of composite bleeding events increased with a higher HAS-BLED score (HR: 1.62, 95% CI: 1.02-2.63). Moreover, 34.3% of warfarin users maintained a percent time in therapeutic range of above 50%. Furthermore, 77.9% of DOAC users received appropriate dosing. No significant differences were observed in terms of the incidence of thrombotic or bleeding events between the two groups during coadministration. In addition, a higher HAS-BLED score was associated with a greater risk of bleeding events regardless of the class of OACs used. Finally, close monitoring of bleeding events should be considered.

Real-World Clinical Outcomes of Warfarin Use Among Patients with Chronic Kidney Disease in Thailand

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. Keywords: Vitamin K antagonist; Bleeding; Thromboembolism; Chronic kidney disease

Characteristics and outcomes in elderly patients with non-valvular atrial fibrillation and high bleeding risk: subanalysis of the J-RHYTHM Registry

Recently, a once-daily dose of edoxaban (15-mg) has been approved for stroke prevention in non-valvular atrial fibrillation (NVAF) patients aged ≥ 80 years, in whom standard oral anticoagulants are not recommended because of high bleeding risk (HBR), based on the ELDERCARE-AF trial. However, information regarding the characteristics and clinical outcomes among such patients is limited. Thus, this study aimed to clarify the characteristics and event rates in elderly patients with NVAF and HBR defined by the ELDERCARE-AF criteria. Of the 7406 NVAF outpatients included in the J-RHYTHM Registry, 60 patients with creatinine clearance (CrCl) < 15 mL/min were excluded. The remaining 7346 patients (age, 69.7 ± 9.9 years; men, 70.9%; warfarin use, 78.7%) were divided into three groups: Group 1, aged < 80 years (n = 6165); Group 2, aged ≥ 80 years without HBR (n = 584); and Group 3, aged ≥ 80 years with HBR (at least one of the followings; CrCl, 15–30 mL/min, history of bleeding, body weight ≤ 45 kg, and antiplatelet use) (n = 597, eligible for 15-mg edoxaban). Patients in Group 3 had a higher prevalence of comorbidities, and therefore, both higher thromboembolic and bleeding risk scores than in the other groups. During the 2-year follow-up period, the incidence rates (per 100 person-years) of thromboembolism in Groups 1, 2, and 3 were 0.7, 1.5, and 2.1 (P < 0.001), major hemorrhage, 0.8, 1.2, and 2.0 (P < 0.001), and all-cause death, 0.8, 2.6, and 4.6 (P < 0.001), respectively. Adjusted hazard ratios of Group 3 were 1.64 (95% confidence interval 0.89–3.04, P = 0.116) for thromboembolism, 1.53 (0.85–2.72, P = 0.154) for major hemorrhage, and 1.84 (1.19–2.85, P = 0.006) for all-cause death compared with Group 1. The NVAF Patients aged ≥ 80 years with HBR defined by the ELDERCARE-AF criteria were certainly at a higher adverse event risk, especially for all-cause death. Clinical trial registration: The J-RHYTHM Registry is registered in the University Hospital Medicine Information Network (UMIN) Clinical Trials Registry (unique identifier: UMIN000001569) http://www.umin.ac.jp/ctr/.

Application of the U.S. Food and Drug Administration's Sentinel Routine Querying Tools to the Taiwan Sentinel Data Model-formatted National Health Insurance Research Database.

The U.S. Food and Drug Administration's Sentinel System is a leading distributed data network for drug safety surveillance in the world. The National Health Insurance Research Database (NHIRD) in Taiwan was converted into the Taiwan Sentinel Data Model (TSDM) based on the Sentinel Common Data Model (SCDM) version 6.0.2. The goal of this study was to investigate the feasibility of applying the same study designs, analytic choices, and analytic tools as used by the U.S. Sentinel System to examine the same drug-outcome associations in the TSDM-formatted NHIRD. Four known drug-outcome associations previously examined by the U.S. Sentinel System were selected as the use cases: (1) use of angiotensin-converting enzyme inhibitors (ACEIs) and risk of angioedema, (2) use of warfarin and risk of gastrointestinal bleeding, (3) use of oral clindamycin and risk of Clostridioides difficile infection (CDI), and (4) use of glyburide and risk of serious hypoglycemia. We followed the same study designs and analytic choices used by the U.S. Sentinel System and applied the Sentinel Routine Querying Tools to answer the same study questions within the TSDM-formatted NHIRD. The results showed that ACEIs were associated with a non-significant increase in risk of angioedema compared to beta-blockers (hazard ratio [HR]: 1.21; 95% confidence interval [CI]: 0.89-1.64); warfarin was associated with a higher risk of gastrointestinal bleeding compared to statins (HR: 1.72; 1.50-1.98); glyburide was associated with an increased risk of hypoglycemia compared to glipizide (HR: 1.61, 1.30-2.00). We were unable to evaluate the association between oral clindamycin and risk of CDI due to the low event number. Our study demonstrated that it was feasible to directly apply the publicly available Sentinel Routine Querying Tools within the TSDM-formatted NHIRD. However, sources of heterogeneity other than design and analytic differences should be carefully considered when comparing the results between the two systems.

Clinical Predictors of Gastrointestinal Bleeding Source before Computed Tomography Angiography.

Acute gastrointestinal bleeding (GIB) is a commonly encountered medical emergency. In cases of negative endoscopic evaluations, computed tomography angiography (CTA) is usually the next diagnostic step. To date, data regarding positive CTA examinations are lacking. We aimed to assess the clinical and laboratory parameters that predict a positive CTA examination, as demonstrated by the extravasation of contrast material into the bowel lumen. We performed a single-center retrospective study, including all patients who were admitted with GIB and who underwent CTA. Analysis was performed to compare patients' characteristics, and logistic regression was used to explore parameters associated with a positive CTA. We included 154 patients. Of them, 25 patients (16.2%) had active GIB on CTA vs. 129 patients (83.8%) who did not. On univariate analysis, several parameters were positively associated with active GIB, including congestive heart failure (OR 2.47, 95% CI 1.04-5.86, p = 0.04), warfarin use (OR 4.76, 95% CI 1.49-15.21, p = 0.008), higher INR (OR 1.33, 1.04-1.69, p = 0.02), and low albumin level (OR 0.37, 95% CI 0.17-0.79, p = 0.01). On multivariate logistic regression analysis, only high INR (OR 1.34, 95% CI 1.02-1.76, p = 0.03) and low albumin (OR 0.3, 95% CI 0.12-0.7, p = 0.005) kept their positive association with active bleeding, while a high ASA score was negatively associated with an active GIB. We could identify high INR and low albumin as strong predictors of active GIB, as demonstrated by positive CTA. On the other hand, comorbid patients classified by a high ASA score did not experience a higher rate of active GIB.

Benefit of Anticoagulation Early After Surgical Aortic Valve Replacement Using Bioprosthetic Valves.

To compare all-cause mortality and thromboembolic events in patients undergoing surgical aortic valve replacement (sAVR) receiving anticoagulation with warfarin versus patients with no systemic anticoagulation. Using data from the OptumLabs Data Warehouse, we investigated adult patients having bioprosthetic sAVR with or without coronary artery bypass from January 1, 2007, through December 31, 2019. Patients were classified into groups of nonwarfarin or warfarin (≥30 days of continuous prescription coverage after sAVR). One-to-one propensity score (PS) matching was used to adjust for group differences. Of 10,589 patients having sAVR, 7659 (72.3%) were in the nonwarfarin group and 2930 (27.7%) were in the warfarin group. After PS matching, 2930 pairs of patients were analyzed. Median follow-up was 4.1 months (interquartile range [IQR], 2.6-7.4 months) for the warfarin group and 21.3 months (IQR, 7.8-24.0 months) for the nonwarfarin group. Overall mortality was lower for the warfarin group than for the nonwarfarin group (hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.47 to 1.00; P=.047), and there was a trend toward decreased cumulative incidence of thromboembolic events (subdistribution HR [SHR], 0.62; 95% CI, 0.35 to 1.07; P=.09). Cumulative incidence of major bleeding events was higher for the warfarin group vs the nonwarfarin group (SHR, 1.94; 95% CI, 1.28 to 2.94; P=.002). Results were similar in a subgroup analysis of patients undergoing isolated sAVR. During the prescription coverage period, warfarin use after bioprosthetic sAVR was associated with lower all-cause mortality and decreased risk of thromboembolism compared with not receiving warfarin. However, warfarin use was associated with an increased risk of major bleeding events.