Warfarin Initiation Research Articles

Impact of Antibacterials on the Quality of Anticoagulation Control in Patients Initiating Warfarin Therapy.

Warfarin interacts with antibacterials to prolong the prothrombin time international normalized ratio (PT-INR) and increase the risk of bleeding. Patients initiating warfarin therapy often undergo precise dosage adjustments; however, the clinical implications of these interactions with antibacterials remain unclear. This study aimed to clarify the effect of antibacterials on PT-INR during the warfarin induction phase. This was a retrospective, observational study. Patients who were newly treated with warfarin after cardiovascular surgery were included. The primary endpoint was the comparison of the maximum PT-INR and time in therapeutic range (TTR) after warfarin initiation between the antibacterial-treated (ABx) and non-treated (non-ABx) groups. The maximum PT-INR was significantly higher in the ABx group (which included β-lactams, glycopeptides, quinolones, tetracyclines, and aminoglycosides) than in the non-ABx group (median [interquartile range] 2.37 [2.03-2.71] vs. 2.08 [1.93-2.33]; P = 0.005); however, the TTR did not differ significantly (65% [44-76] vs. 71% [43-85]; P = 0.150). The odds ratio for maximum PT-INR >2.6 with antimicrobial therapy was 2.51 (95% confidence interval 1.21-5.21). Antibacterial therapy was a risk factor for a maximum PT-INR >2.6. However, there was no association with the TTR, which is a marker of good outcomes. This was due to the strict warfarin dosing regimen according to the algorithm, which immediately and appropriately adjusted for PT-INR overexpansion. Antibacterials have been suggested to increase PT-INR during the induction phase of warfarin. However, with strict dose adjustments, the clinical impact on the PT-INR and TTR is likely limited.

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

PurposeTo 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. MethodsA 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. ResultsThe 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)]. ConclusionCYP2C9 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.

Comparative Effectiveness and Safety of Apixaban, Rivaroxaban, and Warfarin in Patients With Cirrhosis and Atrial Fibrillation : A Nationwide Cohort Study.

Apixaban, rivaroxaban, and warfarin have shown benefit for preventing major ischemic events, albeit with increased bleeding risk, among patients in the general population with atrial fibrillation (AF). However, data are scarce in patients with cirrhosis and AF. To compare the effectiveness and safety of apixaban versus rivaroxaban and versus warfarin in patients with cirrhosis and AF. Population-based cohort study. Two U.S. claims data sets (Medicare and Optum's de-identified Clinformatics Data Mart Database [2013 to 2022]). 1:1 propensity score (PS)-matched patients with cirrhosis and nonvalvular AF initiating use of apixaban, rivaroxaban, or warfarin. Primary outcomes included ischemic stroke or systemic embolism and major hemorrhage (intracranial hemorrhage or major gastrointestinal bleeding). Database-specific and pooled PS-matched rate differences (RDs) per 1000 person-years (PY) and Cox proportional hazard ratios (HRs) with 95% CIs were estimated, controlling for 104 preexposure covariates. Rivaroxaban initiators had significantly higher rates of major hemorrhagic events than apixaban initiators (RD, 33.1 per 1000 PY [95% CI, 12.9 to 53.2 per 1000 PY]; HR, 1.47 [CI, 1.11 to 1.94]) but no significant differences in rates of ischemic events or death. Consistently higher rates of major hemorrhage were found with rivaroxaban across subgroup and sensitivity analyses. Warfarin initiators also had significantly higher rates of major hemorrhage than apixaban initiators (RD, 26.1 per 1000 PY [CI, 6.8 to 45.3 per 1000 PY]; HR, 1.38 [CI, 1.03 to 1.84]), particularly hemorrhagic stroke (RD, 9.7 per 1000 PY [CI, 2.2 to 17.2 per 1000 PY]; HR, 2.85 [CI, 1.24 to 6.59]). Nonrandomized treatment selection. Among patients with cirrhosis and nonvalvular AF, initiators of rivaroxaban versus apixaban had significantly higher rates of major hemorrhage and similar rates of ischemic events and death. Initiation of warfarin versus apixaban also contributed to significantly higher rates of major hemorrhagic events, including hemorrhagic stroke. National Institutes of Health.

Veterans Affairs Medical Center Racial and Ethnic Composition and Initiation of Anticoagulation for Atrial Fibrillation

Racial and ethnic disparities exist in anticoagulation therapy for atrial fibrillation (AF). Whether medical center racial and ethnic composition is associated with these disparities is unclear. To determine whether medical center racial and ethnic composition is associated with overall anticoagulation and disparities in anticoagulation for AF. Retrospective cohort study of Black, White, and Hispanic patients with incident AF from 2018 to 2021 at 140 Veterans Health Administration medical centers (VAMCs). Data were analyzed from March to November 2023. VAMC racial and ethnic composition, defined as the proportion of patients from minoritized racial and ethnic groups treated at a VAMC, categorized into quartiles. VAMCs in quartile 1 (Q1) had the lowest percentage of patients from minoritized groups (ie, the reference group). The odds of initiating any anticoagulant, direct-acting oral anticoagulant (DOAC), or warfarin therapy within 90 days of an index AF diagnosis, adjusting for sociodemographics, medical comorbidities, and facility factors. The cohort comprised 89 791 patients with a mean (SD) age of 73.0 (10.1) years; 87 647 (97.6%) were male, 9063 (10.1%) were Black, 3355 (3.7%) were Hispanic, and 77 373 (86.2%) were White. Overall, 64 770 individuals (72.1%) initiated any anticoagulant, 60 362 (67.2%) initiated DOAC therapy, and 4408 (4.9%) initiated warfarin. Compared with White patients, Black and Hispanic patients had lower rates of any anticoagulant and DOAC therapy initiation but higher rates of warfarin initiation across all quartiles of VAMC racial and ethnic composition. Any anticoagulant therapy initiation was lower in Q4 than Q1 (69.8% vs 74.9%; adjusted odds ratio [aOR], 0.80; 95% CI, 0.69-0.92; P < .001). DOAC and warfarin initiation were also lower in Q4 than in Q1 (DOAC, 69.4% vs 65.3%; aOR, 0.85; 95% CI, 0.74-0.97; P < .001; warfarin, 5.4% vs 4.5%; aOR, 0.82; 95% CI, 0.67-1.00; P < .001). In adjusted models, patients in Q4 were significantly less likely to initiate any anticoagulant therapy than those in Q1 (aOR, 0.88; 95% CI, 0.78-0.99). Patients in Q3 (aOR, 0.75; 95% CI, 0.60-0.93) and Q4 (aOR, 0.69; 95% CI, 0.55-0.87) were significantly less likely to initiate warfarin therapy than those in Q1. There was no significant difference in the adjusted odds of initiating DOAC therapy across racial and ethnic composition quartiles. Although significant Black-White and Hispanic-White differences in initiation of any anticoagulant, DOAC, and warfarin therapy were observed, interactions between patient race and ethnicity and VAMC racial composition were not significant. In a national cohort of VA patients with AF, initiation of any anticoagulant and warfarin, but not DOAC therapy, was lower in VAMCs serving more minoritized patients.

Evaluation of the four mg warfarin initiation dose in patients with cardiovascular disease

Background: Warfarin is the most widely used oral anticoagulant for the prevention of stroke in patients with cardiovascular disease. In Indonesia, validation of the initiation dose of warfarin has never been carried out. Objective: To evaluate the efficacy and safety of 4 mg warfarin initiation dose in achieving therapeutic targets. Methods: It was a prospective observational study involving hospitalised and ambulatory patients administered a 4 mg warfarin initiation dose between days one and three. On day four, the INR was measured for three to seven days. Subsequently, the initiation dose was adjusted to the therapeutic INR. The INR level was measured every seven days until patients achieved therapeutic INR twice. Results: A total of 14 patients were included in this study, with a mean age of 62 years. The most common indication for using warfarin was non-valvular atrial fibrillation (85.7%), with a CHA2DS2-VASc score between one and three and a HAS-BLED score ranging from zero to two. The median time to achieve therapeutic INR was 22.2 days, and the predictive value of the day four INR for determining the maintenance dose had an r2= 0.77. Conclusions: The initiation dose of 4 mg warfarin effectively achieved therapeutic INR within an acceptable time.

Leveraging QSP Models for MIPD: A Case Study for Warfarin/INR.

Warfarin dosing remains challenging due to substantial inter-individual variability, which can lead to unsafe or ineffective therapy with standard dosing. Model-informed precision dosing (MIPD) can help individualize warfarin dosing, requiring the selection of a suitable model. For models developed from clinical data, the dependence on the study design and population raises questions about generalizability. Quantitative system pharmacology (QSP) models promise better extrapolation abilities; however, their complexity and lack of validation on clinical data raise questions about applicability in MIPD. We have previously derived a mechanistic warfarin/international normalized ratio (INR) model from a blood coagulation QSP model. In this article, we evaluated the predictive performance of the warfarin/INR model in the context of MIPD using an external dataset with INR data from patients starting warfarin treatment. We assessed the accuracy and precision of model predictions, benchmarked against an empirically based reference model. Additionally, we evaluated covariate contributions and assessed the predictive performance separately in the more challenging outpatient data. The warfarin/INR model performed comparably to the reference model across various measures despite not being calibrated with warfarin initiation data. Including CYP2C9 and/or VKORC1 genotypes as covariates improved the prediction quality of the warfarin/INR model, even after assimilating 4 days of INR data. The outpatient INR exhibited higher unexplained variability, and predictions slightly exceeded observed values, suggesting that model adjustments might be necessary when transitioning from an inpatient to an outpatient setting. Overall, this research underscores the potential of QSP-derived models for MIPD, offering a complementary approach to empirical model development.

A Randomized Trial Comparing Standard of Care to Bayesian Warfarin Dose Individualization.

The quality of warfarin treatment may be improved if management is guided by the use of models based upon pharmacokinetic-pharmacodynamic theory. A prospective, two-armed, single-blind, randomized controlled trial compared management aided by a web-based dose calculator (NextDose) with standard clinical care. Participants were 240 adults receiving warfarin therapy following cardiac surgery, followed up until the first outpatient appointment at least 3 months after warfarin initiation. We compared the percentage of time spent in the international normalized ratio acceptable range (%TIR) during the first 28 days following warfarin initiation, and %TIR and count of bleeding events over the entire follow-up period. Two hundred thirty-four participants were followed up to day 28 (NextDose: 116 and standard of care: 118), and 228 participants (114 per arm) were followed up to the final study visit. Median %TIR tended to be higher for participants receiving NextDose guided warfarin management during the first 28 days (63 vs. 56%, P = 0.13) and over the entire follow-up period (74 vs. 71%, P = 0.04). The hazard of clinically relevant minor bleeding events was lower for participants in the NextDose arm (hazard ratio: 0.21, P = 0.041). In NextDose, there were 89.3% of proposed doses accepted by prescribers. NextDose guided dose management in cardiac surgery patients requiring warfarin was associated with an increase in %TIR across the full follow-up period and fewer hemorrhagic events. A theory-based, pharmacologically guided approach facilitates higher quality warfarin anticoagulation. An important practical benefit is a reduced requirement for clinical experience of warfarin management.

Patient Characteristics Associated With Using Transcatheter Left Atrial Appendage Occlusion Versus Oral Anticoagulants for Atrial Fibrillation.

Transcatheter left atrial appendage occlusion (LAAO) is an alternative to oral anticoagulants (OACs) for stroke prevention in patients with atrial fibrillation, but the predictors of LAAO use in routine care are unclear. We aimed to assess the utilization trends of LAAO and compare the change in characteristics of LAAO users versus OACs since its marketing. Using the US Medicare claims database (March 15, 2015, to December 31, 2020), we identified patients with atrial fibrillation, ≥65 years, and CHA2DS2-VASc score ≥2 (men) or ≥3 (women), with either first implantation of an LAAO device or initiation of OACs, including apixaban, dabigatran, rivaroxaban, edoxaban, or warfarin. Patient characteristics, measured 365 days before the first LAAO or OAC use date, were compared using logistic regression. There were 30 058 LAAO recipients (mean age, 77.74 years; female, 42.1%) and 792 600 OAC initiators (mean age, 78.48; female, 53.3%). In 2020, patients had higher odds of initiating LAAO use than in 2015 (0.52 versus 9.32%; adjusted odds ratio [aOR], 13.64 [95% CI, 12.56-14.81]). Old age (ie, >85 versus 65-75 years; aOR, 0.84 [95% CI, 0.80-0.88]), female sex (aOR, 0.74 [95% CI, 0.71-0.76]), Black race (aOR, 0.63 [95% CI, 0.58-0.68]) versus White race, and Medicaid eligibility (aOR, 0.61 [95% CI, 0.58-0.64]) were associated with lower odds of receiving LAAO. Among clinical characteristics, frailty, cancer, fractures, and venous thromboembolism were associated with lower odds of LAAO use, while history of intracranial and extracranial bleeding, coagulopathy, and falls were associated with higher odds of receiving LAAO. Among patients with atrial fibrillation receiving stroke-preventive therapy, LAAO use increased rapidly from 2015 to 2020 and was positively associated with the risk factors for OAC complications but negatively associated with old age, advanced frailty, and cancer. Black race and female sex were associated with a lower likelihood of receiving LAAO.

Early Versus Late Post Cesarean Section Warfarin Initiation and Increased Risk of Maternal Complications in Patients With Mechanical Heart Valves: A Randomized, Open-Label Pilot Study.

The timing of the reinstitution of warfarin after cesarean section (CS) delivery was not adequately addressed in the literature. This study aims to evaluate the risks of early versus late initiation of warfarin post-CS in patients with mechanical heart valves. This randomized, open-label cohort study included 114 pregnant women with mechanical heart valves planned to be delivered by CS at or after 28 weeks of gestation. Patients were randomly divided into two groups: Day-2-group, where warfarin was started on day 2, and Day-5-group, where warfarin was started on day 5 after CS. Maternal postoperative bleeding complications, mechanical valve thrombosis, need for blood transfusion or reoperation, and maternal mortality were identified. Ten women (8.8%) had 11 bleeding complications, of whom 2 patients (20%) had intraperitoneal hemorrhage (none in Day-2-group and 2 in Day-5-group), 3 patients (30%) had subcutaneous hematoma (none in Day-2-group and 3 in Day-5-group), and 6 patients (60%) had sub-rectus hematoma (3 in Day-2-group and 3 in Day-5-group). No mechanical valve thrombosis, other thromboembolic events, or in-hospital maternal mortality were reported. Despite the small number of events, the bleeding risk was lower in the group with early post-CS warfarin introduction than in the group with late warfarin introduction in patients with prosthetic heart valves. ClinicalTrials.gov Identifier: NCT04855110.

Warfarin intake in relation to diagnosis reduces mortality in patients with colorectal cancer – a register-based study

BackgroundSeveral studies have analyzed the effect of anticoagulants on cancer survival, with varying results. This study aimed to assess the effect of warfarin on survival in patients with colorectal cancer (CRC) in relation to timing of warfarin initiation. MethodsData on 10,051 individuals aged ≥45 years in the Västra Götaland Region of Sweden, and diagnosed with CRC between 2000 and 2009, were obtained from the Swedish National Cancer Register. Those who received warfarin treatment (n= 1,216) during the study period were labeled cases and those who did not (n= 8,873) were labeled controls. For statistical analysis, National Cancer Register data were merged with mortality data from the Swedish National Cause of Death register and data from the regional warfarin treatment register. ResultsHazard rates for CRC-specific mortality were lower in cases than in controls. When warfarin was used for any reason at any time, cases had a significantly lower CRC-specific mortality than controls among both women (hazard ratio [HR] 0.71; 95 % confidence interval [CI] 0.59–0.85; p= 0.0002) and men (HR 0.61; 95 % CI 0.52–0.72; p < 0001). Warfarin treatment after CRC diagnosis reduced CRC-specific mortality by 80 %; however, when warfarin was given before or ≥5 years after diagnosis, CRC-specific mortality did not significantly decrease. The number needed to treat to avoid one death was four. ConclusionUse of warfarin early after diagnosis in patients with CRC was associated with improved survival.

Effectiveness and safety of apixaban and rivaroxaban vs warfarin in patients with atrial fibrillation and chronic kidney disease.

Randomized controlled trials (RCTs) of direct oral anticoagulants (DOACs) included a low proportion of atrial fibrillation (AF) patients with chronic kidney disease (CKD), and suggested that DOACs are safe and effective in patients with mild-to-moderate CKD. In a metanalysis of RCTs and observational studies, DOACs were associated with better efficacy (vs warfarin) in early CKD and had similar efficacy and safety profiles in patients with stages IV-V CKD. But few studies have provided data on the safety and effectiveness of each DOAC vs warfarin in patients with stage III CKD. The effectiveness and safety of DOACs in those patients are still subject to debate. To assess and compare the effectiveness and safety of apixaban and rivaroxaban vs warfarin in this patient population. A cohort of patients with an inpatient or outpatient code for AF and stage III CKD who were newly prescribed apixaban and rivaroxaban was created using the administrative databases from the Quebec province of Canada between 2013 and 2017. The primary effectiveness outcome was a composite of ischemic stroke, systemic embolism, and death, whereas the primary safety outcome was a composite of major bleeding within a year of DOAC vs warfarin initiation. Treatment groups were compared in an under-treatment analysis using inverse probability of treatment weighting and Cox proportional hazards. A total of 8899 included patients filled out a new oral anticoagulation therapy claim; 3335 for warfarin and 5564 for DOACs. Compared with warfarin, 15 mg and 20 mg rivaroxaban presented a similar effectiveness and safety composite risk. Apixaban 5.0 mg was associated with a lower effectiveness composite risk [Hazard ratio (HR) 0.76; 95% confidence interval (CI): 0.65-0.88] and a similar safety risk (HR 0.94; 95%CI: 0.66-1.35). Apixaban 2.5 mg was associated with a similar effectiveness composite (HR 1.00; 95%CI: 0.79-1.26) and a lower safety risk (HR 0.65; 95%CI: 0.43-0.99. Although, apixaban 5.0 mg was associated with a better effectiveness (HR 0.76; 95%CI: 0.65-0.88), but a similar safety risk profile (HR 0.94; 95%CI: 0.66-1.35). The observed improvement in the effectiveness composite for apixaban 5.0 mg was driven by a reduction in mortality (HR 0.61; 95%CI: 0.43-0.88). In comparison with warfarin, rivaroxaban and apixaban appear to be effective and safe in AF patients with stage III CKD.

COVID-19 pandemic and initiation of treatment for atrial fibrillation: a nationwide analysis of claims data

BackgroundThe COVID-19 pandemic profoundly disrupted the delivery of medical care. It remains unclear whether individuals diagnosed with new onset disease during the pandemic were less likely to initiate treatments after diagnosis. We sought to evaluate changes in the treatment initiation of patients newly diagnosed with atrial fibrillation (AF) after the onset of the COVID-19 pandemic.MethodsIn this retrospective cohort study, we identified individuals with incident AF from 01/01/2016–09/30/2021 using Optum’s de-identified Clinformatics® Data Mart Database. The primary outcome was initiation of oral anticoagulation (OAC) within 30 days of AF diagnosis. Secondary outcomes included initiation of OAC within 180 days of diagnosis, initiation of warfarin, direct oral anticoagulants (DOACs), rhythm control medications and electrical cardioversion within 30 days of diagnosis. We constructed interrupted time series analyses to examine changes in the outcomes following the onset of the pandemic.ResultsA total of 573,524 patients (age 73.0 ± 10.9 years) were included in the study. There were no significant changes in the initiation of OAC, DOAC, and rhythm control medications associated with the onset of the pandemic. There was a significant decrease in initiation of electrical cardioversion associated with the onset of the pandemic. The rate of electronic cardioversion within 30 days of diagnosis decreased by 4.9% per 1,000 patients after the onset of the pandemic and decreased by about 35% in April 2020, compared to April 2019, from 5.53% to 3.58%.ConclusionThe COVID-19 pandemic did not affect the OAC initiation within 30 days of AF diagnosis but was associated with a decline in the provision of procedures for patients newly diagnosed with AF.

Initiation of warfarin is associated with decreased mortality in patients with infective endocarditis: A population-based cohort study

ImportanceThe use of warfarin to prevent thromboembolism in patients with infective endocarditis (IE) remains controversial due to potentially increased bleeding risks. DesignPopulation-based retrospective cohort study. ParticipantsPatients aged 18 or older and diagnosed with IE in Hong Kong between January 1st, 1997 and August 31st, 2020 were included. Patients with use of any anticoagulant 30 days before IE diagnosis were excluded. Patients initiated on warfarin within 14 days of IE diagnosis and patients without warfarin use were matched for baseline characteristics using 1:1 propensity score matching. ExposureWarfarin use within 14 days of IE diagnosis. Main outcomes and measuresPatients were followed up to 90 days for the outcomes of ischemic stroke, all-cause mortality, intracranial hemorrhage, and gastrointestinal bleeding. Cox regression was used to determine hazard ratios (HRs) [95 % confidence intervals (CIs)] between treatment groups. Fine-Gray competing risk regression with all-cause mortality as the competing event was performed as a sensitivity analysis. In addition to 90-day analyses, landmark analyses were performed at 30 days of follow-up. ResultsThe matched cohort consisted of 675 warfarin users (57.0 % male, age 59 ± 16 years) and 675 warfarin non-users (53.5 % male, age 61 ± 19 years). Warfarin users had a 50 % decreased 90-day risk in all-cause mortality (HR:0.50 [0.39–0.65]), without significantly different 90-day risks of ischemic stroke (HR:1.04 [0.70–1.53]), intracranial hemorrhage (HR:1.25 [0.77–2.04]), and gastrointestinal bleeding (HR:1.04 [0.60–1.78]). Thirty-day landmark analysis showed similar results. Competing risk regression showed significantly higher 30-day cumulative incidence of intracranial hemorrhage in warfarin users (sub-HR:3.34 [1.34–8.31]), but not at 90-day (sub-HR:1.63 [0.95–2.81]). Results from Fine-Gray regression were otherwise congruent with those from Cox regression. Conclusions and relevanceWarfarin initiated within 14 days of IE diagnosis was associated with significantly decreased risks of mortality but higher risks of intracranial hemorrhage, with similar risks of ischemic stroke and gastrointestinal bleeding, compared with non-use of warfarin with 14 days of IE diagnosis. Key pointsQuestion: Is warfarin, initiated within 14 days of a diagnosis of infective endocarditis (IE), efficacious and safe?Findings: In this propensity score-matched, population-based, prospective cohort study from Hong Kong, warfarin use within 14 days of IE diagnosis was associated with a 50 % decrease in the risk of all-cause mortality, albeit with higher risk of intracranial hemorrhage, and without significant differences in the risk of ischaemic stroke and gastrointestinal bleeding.Meaning: In patients with IE, warfarin use within 14 days of diagnosis may have mortality benefits, despite increased risks of intracranial hemorrhage.

Initiation of warfarin is associated with decreased mortality in patients with infective endocarditis: a population based cohort study

Abstract Background The use of warfarin as an anticoagulant to prevent thromboembolism in setting of infective endocarditis (IE) remains controversial due to increased bleeding risks. Purpose To study the risks of stroke, mortality and bleeding in warfarin users compared with non-use. Methods Patients aged 18 or older and diagnosed with IE in our city between January 1st 1997 and August 31st 2020 were included. Patients with use of any anticoagulant 30 days before IE diagnosis were excluded. Patients initiated on warfarin within 14 days of IE diagnosis and patients without warfarin use were matched using propensity scores (1:1 ratio). The study outcomes were ischemic stroke, all-cause mortality, intracranial hemorrhage, and gastrointestinal bleeding. Cox proportional hazards regression was used to determine the hazard ratios [95% confidence intervals (CIs)] for the predictors of study outcomes at the end of 90-day follow up. Results The matched cohort consisted of 675 warfarin users (57.0% male, age 59±16 years, mean CHA2DS2-VASc score: 1.42±1.72) and 675 warfarin non-users (53.5% male, age 61±19 years, mean CHA2DS2-VASc score: 1.58±1.76). Warfarin use was not associated with ischemic stroke risk (Hazard ratio: 1.04 [95% CI, 0.70-1.53]), but was associated with a 50% decreased risk of all-cause mortality (HR: 0.50 [0.39-0.65]). In terms of bleeding risk, intracranial hemorrhage occurred in 36 (5.3%) warfarin users and in 29 (4.3%) patients warfarin non-users, and gastrointestinal bleeding occurred in 27 (4.0%) warfarin users and in 26 (3.9%) warfarin non-users. Conclusions Warfarin use is associated with decreased risks of mortality but similar risks of ischemic stroke compared with non-use of warfarin in patients with IE.Kaplein Meier curves of study outcomes

Anticoagulation therapy in patients with atrial fibrillation and active cancer

Abstract Background Atrial fibrillation (AF) is common among cancer patients. Oral anticoagulation therapy (OAT) is important to prevent stroke in AF patients, but active cancer may also predispose to bleeding. Current knowledge on the use of OAT among AF patients with active cancer is scarce. Purpose To assess the influence of active cancer on the initiation of OAT in patients with AF and to explore cancer features predicting withholding OAT. Methods The nationwide FinACAF registry linked data from several registries covering all levels of care as well as drug purchases and included all 123 618 patients diagnosed with incident AF in Finland during 2011- 2018 with an indication for OAT (≥1 non-sex CHA2DS2-VASc point). Patients were considered to have active cancer if they had received a new cancer diagnosis or treatment for cancer during the preceding year from AF diagnosis. The primary outcome was the initiation of OAT (including non-vitamin K oral anticoagulants (NOAC) and warfarin) and the secondary outcome the initiation of any anticoagulation therapy (AAT; including OAT and low molecular-weight heparin) during the first year from AF diagnosis. Results The mean age of the patients was 73.9 (standard deviation 11.5) years and 62 955 (50.9%) of them were women. Altogether, 7015 (5.7%) patients had active cancer at AF diagnosis. The median CHA2DS2-VASc (3 [interquartile range 2-4] for both groups) and HAS-BLED (2 [interquartile range 2-3] for both groups) scores were similar in patients with active cancer and those without cancer history. Patients with active cancer, compared to those without cancer history, less often initiated OAT (47.7% vs. 70.5 %) or AAT (61.8% vs. 71.8%) (Figure). In Fine-Gray regression analyses with all-cause mortality as a competing risk, after adjusting for confounding factors, active cancer remained associated with lower likelihood of OAT (adjusted subdistribution hazard ratio (aSHR 0.501) (95% confidence interval (CI): 0.485-0.518), p&amp;lt;0.001) as well as AAT (aSHR 0.745 (95%-CI 0.723-0.769, p&amp;lt;0.001) initiation. Among cancer patients, metastases, gastrointestinal cancer and radiotherapy were associated with lower likelihood of OAT initiation, while only metastases predicted lower likelihood of AAT initiation (Table). Among patients initiating OAT, active cancer was associated with lesser likelihood of choosing a NOAC over warfarin compared to those without cancer (36.0% vs. 39.2%; adjusted hazard ratio 0.712 (95%-CI: 0.640-0.792), p&amp;lt;0.001). Conclusion AF patients with active cancer are less likely to initiate anticoagulation therapy, and those starting OAT are less likely to initiate with NOACs, compared to patients without cancer history. Metastases are the most important predictor of withholding anticoagulation therapy among AF patients with cancer.

Comparative Safety and Effectiveness of Warfarin or Rivaroxaban Versus Apixaban in Patients With Advanced CKD and Atrial Fibrillation: Nationwide US Cohort Study

Head-to-head data comparing the effectiveness and safety of oral anticoagulants in patients with atrial fibrillation (AF) and advanced chronic kidney disease (CKD) are lacking. We compared the safety and effectiveness of warfarin or rivaroxaban versus apixaban in patients with AF and non-dialysis-dependent CKD stage 4/5. Propensity score-matched cohort study. 2 nationwide US claims databases, Medicare and Optum's deidentified Clinformatics Data Mart Database, were searched for the interval from January 1, 2013, through March 31, 2022, for patients with nonvalvular AF and CKD stage 4/5 who initiated warfarin versus apixaban (matched cohort, n=12,488) and rivaroxaban versus apixaban (matched cohort, n= 5,720). Warfarin, rivaroxaban, or apixaban. Primary outcomes included major bleeding and ischemic stroke. Secondary outcomes included all-cause mortality, major gastrointestinal bleeding, and intracranial bleeding. Cox regression was used to estimate HRs, and 1:1 propensity-score matching was used to adjust for 80 potential confounders. Compared with apixaban, warfarin initiation was associated with a higher rate of major bleeding (HR, 1.85; 95% CI, 1.59-2.15), including major gastrointestinal bleeding (1.86; 1.53-2.25) and intracranial bleeding (2.15; 1.42-3.25). Compared with apixaban, rivaroxaban was also associated with a higher rate of major bleeding (1.69; 1.33-2.15). All-cause mortality was similar for warfarin (1.08; 0.98-1.18) and rivaroxaban (0.94; 0.81-1.10) versus apixaban. Furthermore, no statistically significant differences for ischemic stroke were observed for warfarin (1.14; 0.83-1.57) or rivaroxaban (0.71; 0.40-1.24) versus apixaban, but the CIs were wide. Similar results were observed for warfarin versus apixaban in the positive control cohort of patients with CKD stage 3, consistent with randomized trial findings. Few ischemic stroke events, potential residual confounding. In patients with AF and advanced CKD, rivaroxaban and warfarin were associated with higher rates of major bleeding compared with apixaban, suggesting a superior safety profile for apixaban in this high-risk population. Different anticoagulants have been shown to reduce the risk of stroke in patients with atrial fibrillation, such as warfarin and direct oral anticoagulants like apixaban and rivaroxaban. Unfortunately, the large-scale randomized trials that compared direct anticoagulants versus warfarin excluded patients with advanced chronic kidney disease. Therefore, the comparative safety and effectiveness of warfarin, apixaban, and rivaroxaban are uncertain in this population. In this study, we used administrative claims data from the United States to answer this question. We found that warfarin and rivaroxaban were associated with increased risks of major bleeding compared with apixaban. There were few stroke events, with no major differences among the 3 drugs in the risk of stroke. In conclusion, this study suggests that apixaban has a better safety profile than warfarin and rivaroxaban.

Abstract P541: Trends in Initiation of Anticoagulation for Atrial Fibrillation in the Early Months of the COVID-19 Pandemic

Introduction: Oral anticoagulation (OAC) is the treatment of choice to prevent stroke in patients with atrial fibrillation (AF). We evaluated changes in OAC initiation in newly diagnosed AF after the onset of the COVID-19 pandemic. Hypothesis: We hypothesized that individuals newly diagnosed with AF in the early months of the COVID-19 pandemic would be less likely to initiate OAC than those with incident AF before the pandemic. Methods: We selected individuals with incident AF in 01/01/2016 - 09/30/2021 from Optum’s de-identified Clinformatics® Data Mart Database. AF was defined by having ICD-9 code 427.31 or ICD-10 codes I48.0, I48.1, I48.2, or I48.91 at the first or second diagnosis field. For every 30-day period. We measured the proportion of individuals newly diagnosed with AF initiated OAC within 30 or 180 days of diagnosis. As secondary outcomes, we evaluated the initiation of warfarin and of direct oral anticoagulants (DOACs) individually. We constructed interrupted time series analyses to examine changes in the level and trend of OAC initiation following the onset of the COVID-19 pandemic, defined by the date of the World Health Organization declaration (3/11/2020). Results: The study sample included 573,524 individuals (age 73± 11 years, 48% female sex, 85% Medicare beneficiaries). Although initiation of OAC and DOAC increased in 01/01/2016-09/30/2021 (Figure), there were no significant changes associated with the onset of pandemic (all P&gt;0.05). Rates of warfarin initiation decreased over time, from 9.7% in year 2016 to 1.9% in year 2021. Conclusion: There were no significant changes in the initiation of OAC immediately after the onset of the COVID-19 pandemic among patients newly diagnosed with AF during this time.

Trends of use and factors that determine the choice of oral anticoagulants in women and men with atrial fibrillation.

The aim was to identify sex-specific factors linked with oral anticoagulant initiation in a cohort of patients with atrial fibrillation using administrative data from Quebec (Canada) between 2014 and 2017. Cohort entry defined as new users, that is, no claims in last 12 months, a cohort of 32 050 patients was stratified in two groups, that is, women and men. Multivariable regression models were used to identify factors of initiations for low- and standard-dose direct oral anticoagulants (DOACs) versus warfarin, and low- versus standard-dose DOACs. In both sexes, warfarin initiation decreased and DOAC initiation increased, with year of initiation as major factors of DOACs use. In 2017, the increase was of 2- to 4-fold and 3- to 8-fold for low- and standard-dose DOACs (vs. warfarin), respectively. The proportion of patients starting on a low-dose DOAC was higher in women than men. Older age for both sexes and CHADS2 score ≥2 (only women) were major factors of low-dose dabigatran and rivaroxaban versus warfarin use. The only significant factor of standard-dose DOAC versus warfarin use was age of 65-79 for women or men treated with apixaban by 1.8- and 1.4-fold, respectively. Factors that made women and men less likely to receive a standard-dose DOAC versus warfarin were higher CHADS2 (for dabigatran and rivaroxaban), HAS-BLED and frailty scores, prior coronary disease, major bleeding, and chronic kidney disease (CKD) status. The choice of a low- versus standard-dose DOAC was mainly driven by age and CKD, and higher CHADS2 score (for dabigatran and apixaban) for both sexes.

Trends in Use of Oral Anticoagulants in Older Adults With Newly Diagnosed Atrial Fibrillation, 2010-2020

Undertreatment of older adults with atrial fibrillation with anticoagulation therapy is an important practice gap. It has been posited that the availability of direct oral anticoagulants (DOACs) would improve oral anticoagulant (OAC) initiation in older adults with atrial fibrillation given their superior safety profile compared with warfarin. To systematically examine trends in OAC initiation and nonadherence in older adults with atrial fibrillation and coexisting geriatric conditions. This retrospective cohort study uses administrative claims data from Optum's Clinformatics Data Mart from January 1, 2010, to December 31, 2020. Participants included beneficiaries of Medicare Advantage plans aged 65 years and older with atrial fibrillation and elevated risk of ischemic stroke. Data analysis was performed from October 2021 to October 2022. Coexisting dementia, frailty, and anemia. The primary outcomes were OAC initiation within 12 months after the first diagnosis of atrial fibrillation per year and nonadherence with OAC per year (defined as <80% of proportion of days covered among patients newly started on OAC in each year). There were 21 603 to 51 236 patients per year (total for 2010-2020, 381 488 patients) in the OAC-eligible incident AF cohort (mean [SD] age, 77.2 [6.1] to 77.4 [6.8] years; 13 871 [51.8%] to 22 901 [49.8%] women). OAC initiation within 12 months after incident AF increased from 20.2% (5405 of 26 782 patients) in 2010 to 32.9% (7111 of 21 603 patients) in 2020. DOAC uptake increased from 1.1% (291 of 26 782 patients) to 30.9% (6678 of 21 603 patients), and warfarin initiation decreased from 19.1% (5114 of 26 782 patients) to 2.0% (436 of 21 603 patients). Older age (odds ratio [OR], 0.98; 95% CI, 0.98-0.98), dementia (OR, 0.57; 95% CI, 0.55-0.58), frailty (OR, 0.74; 95% CI, 0.72-0.76), and anemia (OR, 0.75; 95% CI, 0.74-0.77) were associated with lower odds of OAC initiation. During the study period, the median (IQR) proportion of days covered increased from 77.6% (41.0%-96.4%) to 90.2% (57.4%-98.6%), and OAC nonadherence decreased from 52.2% (2290 of 4389 patients) to 39.0% (3434 of 8798 patients). Since the introduction of DOACs, OAC initiation in older adults with has improved but remained suboptimal in 2020. Additional strategies are needed to improve stroke prophylaxis in all older adults with atrial fibrillation including those with coexisting dementia, frailty, and anemia.

Abstract 9312: Factors That Predict the Choice of Oral Anticoagulants in Men and Women With Atrial Fibrillation

Introduction: Potential sex-specific differences in oral anticoagulation (OAC) initiation among atrial fibrillation (AF) patients discharged from hospital into the community have not previously been investigated. This study identified sex-specific factors associated with OAC initiation in patients with AF. Methods: Using hospitalization and drug databases, we built a cohort of AF patients having been hospitalized and then discharged to the community between 2014 and 2017 in Québec, Canada. The primary outcome was the choice of OAC (warfarin, high-dose or low-dose DOAC) initiated upon hospital discharge, based on the first claim at the index date. Multivariate logistic regression was used to identify predictors of low-dose and standard-dose DOAC vs warfarin initiation, and low-dose vs standard-dose DOACs initiation. Results: 32,050 patients were included, from whom 16,896 (53%) were women. In both sexes, warfarin initiation decreased while DOACs initiation increased over time. 17.3%, 29.0% and 53.7% of women were started on warfarin, low-dose and standard-dose DOACs, respectively while 15.6%, 16.6% and 67.8% of men were started on warfarin, low-dose and standard-dose DOACs, respectively. Year of initiation was a predictor of DOACs (odds ratios (ORs): from 1.40 to 8.37) (vs warfarin initiation in both sex (Table 1). Older age predicted the use of low-dose DOACs vs warfarin in both sex (ORs: from 1.65 to 3.99 age 65-79 and from 1.83 to 10.29 in age ≥80), while a CHA 2 DS 2 -VASc score ≥3 predicted the use of low-dose DOACs in women only (ORs from 1.98 to 2.49). Age ≥80 (ORs: from 17.99 to 64.82) and chronic kidney disease (CKD) (ORs from 2.82 to 7.42) predicted the use of low-dose DOACs vs standard DOACs in both sex (ORs: from 2.64 to 3.29 age. Conclusions: Women were more likely than men to received low-dose DOACs and the decision to initiate low- vs standard-dose DOACs was mainly driven by age, CKD status (in both sexes) and a high CHA 2 DS 2 -VASc score (in women only).