Warfarin Prescription Research Articles

Holistic Approach to Ecstasy-induced Atrial Fibrillation in a Young Patient: A Case Report

Stimulants abuse is a global issue. Acute myocardial infarction, heart failure, and arrhythmia have all been linked to stimulants misuse and its synthetic variants but are rather uncommon. Herein, we present a case of a young patient presented with atrial fibrillation that did not respond to digoxin therapy. A suspicion of drug toxicity was later confirmed with a bedside urine screening. Following administration of benzodiazepines, the patient's clinical condition gradually improved, and he was eventually discharged with a prescription of lifelong warfarin. Therefore, patients with a low-to-intermediate risk of coronary artery disease presenting with atypical symptoms may benefit from a full substance use history and urine drug screening to ensure prompt institution of appropriate treatment.

Improving safety of warfarin prescribing and administration using clinical decision support

Improving safety of warfarin prescribing and administration using clinical decision support

Association of Race and Ethnicity With Oral Anticoagulation and Associated Outcomes in Patients With Atrial Fibrillation

Oral anticoagulation (OAC) is underprescribed in underrepresented racial and ethnic group individuals with atrial fibrillation (AF). Little is known of how differential OAC prescribing relates to inequities in AF outcomes. To compare OAC use at discharge and AF-related outcomes by race and ethnicity in the Get With The Guidelines-Atrial Fibrillation (GWTG-AFIB) registry. This retrospective cohort analysis used data from the GWTG-AFIB registry, a national quality improvement initiative for hospitalized patients with AF. All registry patients hospitalized with AF from 2014 to 2020 were included in the study. Data were analyzed from November 2021 to July 2022. Self-reported race and ethnicity assessed in GWTG-AFIB registry. The primary outcome was prescription of direct-acting OAC (DOAC) or warfarin at discharge. Secondary outcomes included cumulative 1-year incidence of ischemic stroke, major bleeding, and mortality postdischarge. Outcomes adjusted for patient demographic, clinical, and socioeconomic characteristics as well as hospital factors. Among 69 553 patients hospitalized with AF from 159 sites between 2014 and 2020, 863 (1.2%) were Asian, 5062 (7.3%) were Black, 4058 (5.8%) were Hispanic, and 59 570 (85.6%) were White. Overall, 34 113 (49.1%) were women; the median (IQR) age was 72 (63-80) years, and the median (IQR) CHA2DS2-VASc score (calculated as congestive heart failure, hypertension, age 75 years and older, diabetes, stroke or transient ischemic attack, vascular disease, age 65 to 74 years, and sex category) was 4 (2-5). At discharge, 56 385 patients (81.1%) were prescribed OAC therapy, including 41 760 (74.1%) receiving DOAC. OAC prescription at discharge was lowest in Hispanic patients (3010 [74.2%]), followed by Black patients (3935 [77.7%]) Asian patients (691 [80.1%]), and White patients (48 749 [81.8%]). Black patients were less likely than White patients to be discharged while taking any anticoagulant (adjusted odds ratio, 0.75; 95% CI, 0.68-0.84) and DOACs (adjusted odds ratio, 0.73; 95% CI, 0.65-0.82). In 16 307 individuals with 1-year follow up data, bleeding risks (adjusted hazard ratio [aHR], 2.08; 95% CI, 1.53-2.83), stroke risks (aHR, 2.07; 95% CI, 1.34-3.20), and mortality risks (aHR, 1.22; 95% CI, 1.02-1.47) were higher in Black patients than White patients. Hispanic patients had higher stroke risk (aHR, 2.02; 95% CI, 1.38-2.95) than White patients. In a national registry of hospitalized patients with AF, compared with White patients, Black patients were less likely to be discharged while taking anticoagulant therapy and DOACs in particular. Black and Hispanic patients had higher risk of stroke compared with White patients; Black patients had a higher risk of bleeding and mortality. There is an urgent need for interventions to achieve pharmacoequity in guideline-directed AF management to improve overall outcomes.

Delayed intracranial hemorrhage after head injury among elderly patients on anticoagulation seen in the emergency department.

Elderly patients on oral anticoagulation are commonly seen in emergency departments (EDs). Oral anticoagulation, particularly warfarin, is associated with an increased risk of intracranial hemorrhage after head trauma. Data on delayed bleeds in anticoagulated patients are limited. The objective of this study was to examine risk of delayed intracranial hemorrhage in patients presenting to the ED with a head injury anticoagulated with warfarin or a direct oral anticoagulant, compared to patients not anticoagulated. Cohort study using administrative data from Ontario of patients ≥ 65years presenting to theED with a complaint of head injury between 2016 and 2018. The primary outcome was delayed intracranial hemorrhage, defined as a new ICD-10 code for intracranial hemorrhage within 90days of the initial ED visit for a head injurywhere no intracranial hemorrhage was diagnosed. The main exposure variable was oral anticoagulation use, which was a three-level variable (warfarin, direct oral anticoagulants, or no oral anticoagulation). We used multivariable logistic regression to determine the odds of delayed intracranial hemorrhage based on anticoagulation status. 69,321 patients were included: 58,233 (84.0%) had not been prescribed oral anticoagulation, 3081 (4.4%) had a warfarin prescription, and 8007 (11.6%) had a direct oral anticoagulant prescription. Overall, 718 (1.0%) patients had a delayed intracranial hemorrhage within 90days of ED visit for head injury. Among patients not anticoagulated, 586 (1.0%) had a delayed intracranial hemorrhage, 54 (1.8%) patients on warfarin, and 78 (1.0%) patients on a direct oral anticoagulant had a delayed intracranial hemorrhage. There was an increased odds of delayed intracranial hemorrhage with warfarin use compared with no anticoagulation (OR 1.5, 95% CI 1.1-2.1). There was no association between delayed intracranial hemorrhage and direct oral anticoagulant use compared to no anticoagulation (OR 0.9, 95% CI 0.6-1.1). There was an increased odds of delayed intracranial hemorrhage within 90days in older ED head injured patients prescribed warfarin compared to patients not on anticoagulation. direct oral anticoagulant use was not associated with increased risk of delayed intracranial hemorrhage.

275 Prothrombin Complex Concentrate Use in a Rural Health Care Network

Study ObjectivesReversal of warfarin-induced anticoagulation using prothrombin complex concentrate (PCC4) is more rapidly achieved than with traditional methods such as fresh frozen plasma (FFP). In many rural facilities the availability of PCC4 has been limited. A tertiary hospital instituted a program to provide PCC4 to rural sites using an air transport team and pharmacy exchange. We hypothesized that increasing accessibility of PCC4 would shorten time to INR reversal.MethodsThis was a retrospective study with the primary outcome being time to INR reversal (INR ≤ 1.6) from outside hospital admission. Active warfarin prescription, EMS transfer to the tertiary facility, and receipt of anticoagulation reversal between January 2012 and December 2020 were required for inclusion. Patients were grouped by dates before and after implementation of the program in August 2016. Time to event analysis was conducted to compare mean INR reversal times. Propensity score matching was used to match patients in each arm and Chi-square analysis compared variables across groups.ResultsAfter data collection and review, 165 patients were analyzed. There were 44 patients transferred before implementation of the PCC4 exchange program and 121 after. The mean duration to INR reversal was significantly shorter for patients post-exchange (19.03 hours) compared to pre-exchange (38.98 hours) (p=0.0104). There was no significant difference in 30-day mortality between the groups.ConclusionIn rural hospitals, increasing availability of PCC4 using a medication exchange program significantly reduces time to INR reversal in warfarin patients.No, authors do not have interests to disclose Study ObjectivesReversal of warfarin-induced anticoagulation using prothrombin complex concentrate (PCC4) is more rapidly achieved than with traditional methods such as fresh frozen plasma (FFP). In many rural facilities the availability of PCC4 has been limited. A tertiary hospital instituted a program to provide PCC4 to rural sites using an air transport team and pharmacy exchange. We hypothesized that increasing accessibility of PCC4 would shorten time to INR reversal. Reversal of warfarin-induced anticoagulation using prothrombin complex concentrate (PCC4) is more rapidly achieved than with traditional methods such as fresh frozen plasma (FFP). In many rural facilities the availability of PCC4 has been limited. A tertiary hospital instituted a program to provide PCC4 to rural sites using an air transport team and pharmacy exchange. We hypothesized that increasing accessibility of PCC4 would shorten time to INR reversal. MethodsThis was a retrospective study with the primary outcome being time to INR reversal (INR ≤ 1.6) from outside hospital admission. Active warfarin prescription, EMS transfer to the tertiary facility, and receipt of anticoagulation reversal between January 2012 and December 2020 were required for inclusion. Patients were grouped by dates before and after implementation of the program in August 2016. Time to event analysis was conducted to compare mean INR reversal times. Propensity score matching was used to match patients in each arm and Chi-square analysis compared variables across groups. This was a retrospective study with the primary outcome being time to INR reversal (INR ≤ 1.6) from outside hospital admission. Active warfarin prescription, EMS transfer to the tertiary facility, and receipt of anticoagulation reversal between January 2012 and December 2020 were required for inclusion. Patients were grouped by dates before and after implementation of the program in August 2016. Time to event analysis was conducted to compare mean INR reversal times. Propensity score matching was used to match patients in each arm and Chi-square analysis compared variables across groups. ResultsAfter data collection and review, 165 patients were analyzed. There were 44 patients transferred before implementation of the PCC4 exchange program and 121 after. The mean duration to INR reversal was significantly shorter for patients post-exchange (19.03 hours) compared to pre-exchange (38.98 hours) (p=0.0104). There was no significant difference in 30-day mortality between the groups. After data collection and review, 165 patients were analyzed. There were 44 patients transferred before implementation of the PCC4 exchange program and 121 after. The mean duration to INR reversal was significantly shorter for patients post-exchange (19.03 hours) compared to pre-exchange (38.98 hours) (p=0.0104). There was no significant difference in 30-day mortality between the groups. ConclusionIn rural hospitals, increasing availability of PCC4 using a medication exchange program significantly reduces time to INR reversal in warfarin patients.No, authors do not have interests to disclose In rural hospitals, increasing availability of PCC4 using a medication exchange program significantly reduces time to INR reversal in warfarin patients.

Pharmacogenomics implementation in cardiovascular disease in a highly diverse population: initial findings and lessons learned from a pilot study in United Arab Emirates

BackgroundPharmacogenomic (PGx) testing has proved its utility and cost-effectiveness for some commonly prescribed cardiovascular disease (CVD) medications. In addition, PGx-guided dosing guidelines are now available for multiple CVD drugs, including clopidogrel, warfarin, and statins. The United Arab Emirates (UAE) population is diverse and multiethnic, with over 150 nationalities residing in the country. PGx-testing is not part of the standard of care in most global healthcare settings, including the UAE healthcare system. The first pharmacogenomic implementation clinical study in CVD has been approved recently, but multiple considerations needed evaluation before commencing. The current report appraises the PGx-clinical implementation procedure and the potential benefits of pursuing PGx-implementation initiatives in the UAE with global implications.MethodsPatients prescribed one or more of the following drugs: clopidogrel, atorvastatin, rosuvastatin, and warfarin, were recruited. Genotyping selected genetic variants at genes interacting with the study drugs was performed by real-time PCR.ResultsFor the current pilot study, 160 patients were recruited. The genotypes and inferred haplotypes, diplotypes, and predicted phenotypes revealed that 11.9% of the participants were poor CYP2C19 metabolizers, 35% intermediate metabolizers, 28.1% normal metabolizers, and 25% rapid or ultrarapid metabolizers. Notably, 46.9% of our cohort should receive a recommendation to avoid using clopidogrel or consider an alternative medication. Regarding warfarin, only 20% of the participants exhibited reference alleles at VKORC1-1639G > A, CYP2C9*2, and CYP2C9*3, leaving 80% with alternative genotypes at any of the two genes that can be integrated into the warfarin dosing algorithms and can be used whenever the patient receives a warfarin prescription. For statins, 31.5% of patients carried at least one allele at the genotyped SLCO1B1 variant (rs4149056), increasing their risk of developing myopathy. 96% of our cohort received at least one PGx-generated clinical recommendation for the studied drugs.ConclusionThe current pilot analysis verified the feasibility of PGx-testing and the unforeseen high frequencies of patients currently treated with suboptimal drug regimens, which may potentially benefit from PGx testing.

Informed Decision Making for Anticoagulation Therapy for Atrial Fibrillation.

Patients with atrial fibrillation (AF) must decide between warfarin and direct oral anticoagulants (DOACs), a decision involving important tradeoffs. Our objective was to understand whether physicians engage patients in informed decision making for anticoagulants. We performed an analysis of recorded conversations between physicians and anticoagulation-naïve patients in the Verilogue Point-of-Practice database. We assessed the presence of 7 elements of informed decision making, as well as a discussion of financial costs. Of 37 encounters with 21 physicians, 92% resulted in a DOAC prescription and 8% resulted in a warfarin prescription. Seventy percent met criteria for discussion of pros and cons, 70% for discussion of the alternatives, 43% presented the decision, 30% included an assessment of patient understanding, 22% included an explanation of the patient's role in decision making, 22% included an assessment of patient preferences, and 19% included a discussion of uncertainty. Two encounters (5%) included all 7 elements and 9 (24%) included none. Physicians discussed treatment costs with patients in 43% of encounters. We assessed informed decision making in a single encounter. Physicians and patients may have had other discussions that were not captured in our data. Physicians often presented the alternatives but did not generally engage patients in informed decision making. The high rate of DOAC prescriptions is likely the result of physician preferences, as patient preferences were rarely assessed. Strategies to support physicians in engaging patients in informed decision making for anticoagulation are needed. While physicians discussed the alternatives and presented pros and cons with patients, they rarely assessed patient preferences, explained the patient's role in decision making, or addressed uncertainty.The cost of treatment with DOACs versus warfarin was discussed by physicians in less than half of encounters, limiting patients' ability to make informed decisions for anticoagulation.Only 2 encounters (5%) fulfilled all 7 elements of informed decision making.

Risk of osteoporosis in patients with atrial fibrillation with and without oral anticoagulant therapy

Background We aimed to compare the risk of developing osteoporosis in patients prescribed warfarin or direct-acting oral anticoagulants (DOACs) with those with no therapy. Research design and methods We included 37,632 patients aged between 18 and 111 years with a recorded diagnosis of AF between 1 Jan 2013 and 31 Dec 2017. Patients were followed until the diagnosis of osteoporosis, switch or discontinuation of the OAC, last clinical visit, or end of the study period (31 Dec 2018), whichever occurred first. The incidences of new-onset osteoporosis were calculated using the Cox proportional hazards model. Results Of total, 16,995 (45.2%) had no recorded OAC prescription, and 20,637 had a recorded prescription of warfarin (6,609) or DOAC (14,028). Compared with those not prescribed an OAC, the risk of being diagnosed with new-onset osteoporosis increased in patients prescribed warfarin (HR 2.22, 95% CI 2.00-2.47, p<0.001) and DOACs (HR 1.42, 95% CI 1.29-1.58, p<0.001). However, the effect of DOACs was not statistically significant (HR 1.07, 95% CI 0.86-1.33, p<0.535) after excluding patients with at least one recorded prescription of systemic corticosteroids, antiepileptics, or proton pump inhibitors. Conclusions Use of warfarin or DOACs was associated with a significantly increased risk of developing osteoporosis compared with no OAC treatment.

Anticoagulation After Bioprosthetic Aortic Valve Replacement: Are We Following the Guidelines?

BackgroundGuideline-directed medication adherence is considered an important quality measure after cardiac surgery. We evaluated compliance with the American College of Cardiology/American Heart Association guidelines for warfarin use after surgical aortic valve replacement (sAVR) using bioprostheses and examined potential variations in anticoagulation practice over time. MethodsUsing the OptumLabs Data Warehouse, we investigated adult patients having bioprosthetic sAVR with or without coronary artery bypass (2007-2019). Early postoperative warfarin use was defined as ≥30 days of continuous prescription coverage after sAVR. ResultsAmong 10 730 adult patients having sAVR, 3071 (28.6%) received warfarin early postoperatively. Median length of warfarin prescription coverage was 4.5 months (interquartile range, 3.0-8.9 months). However, only 11.1% (736/6634) had warfarin prescription coverage of 3 to 6 months in compliance with the most recent guidelines. Yearly warfarin prescription rate did not change significantly during the 13-year period (P = .386). Compared with patients from the non-warfarin group, those receiving warfarin prescriptions were older and more likely to be male and to have atrial fibrillation, congestive heart failure, chronic pulmonary disease, and CHA2DS2-VASc score ≥2; warfarin use was also greater in patients receiving prescriptions for other cardiac medications (P < .05). ConclusionsAnticoagulation after sAVR as reflected by warfarin prescriptions may be underused; the rates of warfarin use have not changed in the last decade. Although additional studies are needed to confirm the benefit of early anticoagulation after sAVR, these results indicate that guideline recommendations are not followed by most clinicians. The findings highlight a potentially important area for quality improvement.

1048 REDUCING RISK FROM WARFARIN- A COMPLETED AUDIT CYCLE ON NICE COMPLIANCE WITH WARFARIN FOR NVAF IN HOSPITALISED OLDER PEOPLE

Abstract Introduction Traditionally Warfarin has been mainly used for stroke thromboprophylaxis in patients with atrial fibrillation but direct oral anticoagulant (DOAC) are increasingly being used as they have improved safety profiles with comparable efficacy. Recent data from National Reporting and Learning System (NRLS) have discovered safety incidents related to anticoagulation, predominantly Warfarin, contributing in excess of 10% of all medication errors. National institute for clinical excellence (NICE) recommends reassessing anticoagulation choice for patients on Warfarin with poor anticoagulation control, indicated by any of the following: 1 &amp;gt; 2 INR values &amp;lt;1.5 or &amp;gt; 5 or 1 INR value &amp;gt;8, within the past 6 months 2 &amp;gt; Time in therapeutic range (TTR) &amp;lt;65% Intervention An initial retrospective audit on 50 patients on Warfarin for NVAF performed between June—September 18 showed poor compliance with NICE. We reviewed the previous 6 months INR values and recorded any significant deviations outside of the therapeutic range as per NICE. TTR over the last 6 months was calculated using the Rosendaal method. Following departmental audit presentation, a reaudit was carried out between Jan-Aug 2019 to assess improvement. Results Median age was 87.5 compared to 83 in the first audit. Warfarin was correctly continued in 7/38(18%) in the 1st audit which improved to 9/28 (32%) in the second. Number of patients discharged on warfarin with unstable INRs decreased significantly from 26/32 (81%) patients in the 1st audit to 10/24 (42%) in the 2nd. Discussion Our reaudit shows significant reduction in continuation of warfarin on discharge in patients with unstable INRs (p = 0.0043 Fisher exact test). Although, there is a trend towards improvement with NICE compliance; in general, the compliance with NICE remains poor. We suggest geriatricians to proactively review the appropriateness of warfarin prescription and to consider a DOAC in preference to Warfarin in all elderly patients.

Impact of the COVID-19 pandemic on England’s national prescriptions of oral vitamin K antagonist (VKA) and direct-acting oral anticoagulants (DOACs): an interrupted time series analysis (January 2019–February 2021)

Background Direct-acting oral anticoagulants (DOACs) were developed as an alternative to warfarin to treat and prevent thromboembolism, including stroke prevention in non-valvular atrial fibrillation patients. The COVID-19 pandemic could increase the risk of stroke and/or the risk of bleeding in patients due to nonadherence or sub/supra-optimal dosing. Objective To investigate DOAC prescription trends in England’s community settings during the complete first wave of COVID-19 pandemic. Methods Descriptive and interrupted time series (ITS) analyses were conducted to examine the prescription patterns of DOACs (dabigatran, rivaroxaban, apixaban and edoxaban) and warfarin for primary care patients in the English Prescribing Dataset from January 2019 to February 2021, with March 2020 as the cut-off point. Results A 19% increase in mean DOAC’s accompanied with 20% warfarin prescriptions decline was observed. ITS modelling showed an increase in DOAC prescription volume in March 2020 (+7 million items, p = 0.008). The pre-existing upward trend in DOAC prescriptions slowed during the period (-427,000 items, p = 0.007). Apixaban was the most frequently used DOAC and had the largest step-change in March 2020 (+5 million items, p = 0.010). The mean monthly combined cost of DOACs and warfarin was higher during the period. DOAC prescription trends were consistent across England’s regions. Conclusion: The overall oral anticoagulants use in this period was lower than expected, indicating a medical needs gap, possibly due to adherence issues. The potential clinical and logistical consequences warrant further study to identify contributing factors and mitigate avoidable risks.

Survival outcomes with warfarin compared with direct oral anticoagulants in cancer-associated venous thromboembolism in the United States: A population-based cohort study.

BackgroundDirect oral anticoagulants (DOACs) have comparable efficacy with low-molecular-weight heparin (LMWH) for the treatment of cancer-associated venous thromboembolism (VTE). Whether there is a mortality benefit of DOACs compared with warfarin in the management of VTE in cancer is not established.Methods and findingsUtilizing the United States’ Surveillance, Epidemiology, and End Results (SEER)-Medicare linked databases from 2012 through 2016, we analyzed overall survival in individuals diagnosed with a primary gastric, colorectal, pancreas, lung, ovarian, or brain cancer and VTE who received a prescription of DOAC or warfarin within 30 days of VTE diagnosis. Patients were matched 1:2 (DOAC to warfarin) through exact matching for cancer stage and propensity score matching for age, cancer site, cancer stage, and time interval from cancer to VTE diagnosis. The analysis identified 4,274 patients who received a DOAC or warfarin for the treatment of VTE within 30 days of cancer diagnosis (1,348 in DOAC group and 2,926 in warfarin group). Patients were of median age 75 years and 56% female. Within the DOAC group, 1,188 (88%) received rivaroxaban, and 160 (12%) received apixaban. With a median follow-up of 41 months, warfarin was associated with a statistically significantly higher overall survival compared to DOACs (median overall survival 12.0 months [95% confidence interval (CI): 10.9 to 13.5] versus 9.9 months [95% CI: 8.4 to 11.2]; hazard ratio (HR) 0.85; 95% CI: 0.78 to 0.91; p < 0.001). Observed differences in survival were consistent across subgroups of cancer sites, cancer stages, and type of VTE. The study limitations include retrospective design with potential for unaccounted confounders along with issues of generalizability beyond the cancer diagnoses studied.ConclusionsIn this analysis of a population-based registry, warfarin was associated with prolonged overall survival compared to DOACs for treatment of cancer-associated VTE.

Antithrombotic Therapy and the Nearest Forecast of Pulmonary Embolism in Rutine Clinical Practice (Data of the Regional Vascular Center of the Ryazan Region)

Aim. To perform the analysis of antithrombotic therapy and immediate prognosis in patients with pulmonary embolism (PE) in routine clinical practice.Materials and methods. During 13 months of follow-up (2018-2019) within the framework of the Russian SIRENA registry, the study included patients (n=103) with verified PE who were hospitalized at the regional vascular center. Main results. Thrombolytic therapy was performed in 63 patients (61.2% of the sample), of which 48 (76.2%) had no indications. In these cases, the most common reason for performance was the results of the PESI score (n=17) and/or a significant amount of damage to the pulmonary artery (n=10) and/or severe shortness of breath (n=3) and/or the presence of a thrombus in the right parts of the heart or deep veins of the lower extremities (n=2), in addition, in a number of medical records, the cause is indicated as “for health reasons” (n=6) or there were no data (n=10). Patients who underwent thrombolysis had a larger volume of pulmonary lesions, more pronounced signs of respiratory failure and overload of the right heart, as well as a shorter duration of clinical manifestations. Anticoagulant therapy was used in 94.2% of cases, of which 90.3% of patients used parenteral forms at the start, then direct oral anticoagulants were mainly used, the frequency of warfarin prescription was only 5.8% of cases. Bleeding was registered in 19.4% of patients (significant – in 11.7%). PE recurrence after diagnosis and initiation of therapy was observed in 4 cases (3.9%). Hospital mortality was 9.7%. Predictors of poor prognosis were hospitalization with a different diagnosis (risk ratio [RR] 16.2; p=0.001), advanced age (RR 10.1; p=0.028), unstable hemodynamics (RR 7.6; p=0.002), chronic kidney disease C3- 5 (RR 5.6; p=0.03), history of stroke (RR 5.3; p=0.016) and chronic heart failure (RR 3.9; p=0.035).Conclusion. In modern clinical practice, the indications for thrombolysis often differ from those recommended, which leads to an increase in the number of bleeding and leveling of the positive effect on the prognosis. Factors such as advanced age, chronic heart failure and atrial fibrillation, stroke, chronic kidney disease, hemodynamic instability, hospitalizations with a different primary diagnosis, and the need for oxygen therapy increase the risk of early mortality.

Apixaban versus Warfarin for Treatment of Venous Thromboembolism in Patients Receiving Long-Term Dialysis.

The association of apixaban compared with warfarin for the treatment of venous thromboembolism in patients receiving maintenance dialysis is not well studied. We conducted a retrospective cohort study of Medicare fee-for-service beneficiaries receiving dialysis using United States Renal Data System data from 2013 to 2018. The study included patients who received a new prescription for apixaban or warfarin following a venous thromboembolism diagnosis. The outcomes were recurrent venous thromboembolism, major bleeding, and death. Outcomes were analyzed using Cox proportional hazards regression for intention-to-treat and censored-at-drug-switch-or-discontinuation analyses. Models incorporated inverse probability of treatment and censoring weights to minimize confounding and informative censoring. In 12,206 individuals, apixaban, compared with warfarin, was associated with lower risks of both recurrent venous thromboembolism (hazard ratio [HR], 0.58; 95% confidence interval [95% CI], 0.43 to 0.77) and major bleeding (HR, 0.78; 95% CI, 0.62 to 0.98) in the intention-to-treat analysis over 6 months of follow-up. However, there was no difference between apixaban and warfarin in terms of risk of all-cause death (HR, 1.04; 95% CI, 0.94 to 1.16). Corresponding hazard ratios for the 6-month censored-at-drug-switch-or-discontinuation analysis and for corresponding analyses limited to a shorter (3-month) follow-up were all highly similar to the primary analysis. In a large group of US patients on dialysis with recent venous thromboembolism, we observed that apixaban was associated with lower risk of recurrent venous thromboembolism and of major bleeding than warfarin. There was no observed difference in mortality.

Abstract 73: Associations Of Social Determinants Of Health On Anticoagulation Treatment Among Patients With Atrial Fibrillation At Risk For Stroke At A Large Health System

Objectives: The objective of this study was to evaluate anticoagulant prescribing disparities in atrial fibrillation (AF) by exploring associations between social determinants of health (SDOH) collected from electronic health records (EHR) and oral anticoagulant (OAC) prescription. Methods: This retrospective study included adult patients newly diagnosed with AF who had ≥ 2 encounters from a large, integrated healthcare system between May 2016 and May 2021. Patient-level demographics, prescribing provider specialties, comorbidities, medications, and SDOH were extracted from EHRs. Area deprivation index (ADI) was linked to patient records as a measure of socioeconomic status. Patients were followed for 1 year from diagnosis. Multivariable logistic regression models were used to assess associations between SDOH, clinical factors, and OAC prescribing and class (warfarin or direct-acting OAC[DOAC]) of OAC prescribed. Results: Of 19,191 AF patients, 12,718 patients (66.3%) were prescribed an OAC within the first year of diagnosis. Mean age was 71.1 + 12.9 years, 43.9% (8,430 of 19,191) were females, and 91.2% (17,705 of 19,191) were white. Patients were less likely to be prescribed an OAC (relative risk [95% CI]) if they were widowed (0.98 [0.96-0.99] vs single) or had history of alcoholism (0.86 [0.79-0.95] vs no history). Most patients (53.3%) received prescriptions from a primary care provider. A linear relationship was found between worsening ADI and increased warfarin prescriptions compared with DOACs. Conclusion: Though guideline-concordant anticoagulation use remained suboptimal, clinical characteristics were strong predictors if an OAC was prescribed for AF stroke prevention. Worsening ADI was associated with an increased likelihood for patients to be prescribed warfarin instead of a DOAC.

Area Deprivation Index and Oral Anticoagulation in New Onset Atrial Fibrillation

ObjectiveOral anticoagulation is a standard of care for thromboembolic stroke prevention in individuals with atrial fibrillation (AF). Social determinants of health have had limited investigation in AF and particularly in access to anticoagulation. We examined the relation between area deprivation index (ADI) and anticoagulation in individuals at risk of stroke due to AF. MethodsWe conducted a retrospective analysis of patients with incident, non-valvular AF from 2015-2020 receiving care at a large, regional health center. We extracted demographics, medications, and problem lists and used administrative coding to identify comorbid conditions and relevant covariates, and individual-level residential address to ascertain ADI. We examined the relation between ADI and receipt of prescribed oral anticoagulation (warfarin or direct-acting oral anticoagulant, or DOAC) at 90 days following AF diagnosis in multivariable-adjusted models. ResultsFollowing exclusions, the dataset included 20,210 individuals (age 74.5±10.9 years; 51% women; 94% white race). In multivariable-adjusted analyses, individuals in the highest quartile of ADI had a 16% lower likelihood of receiving anticoagulation prescription than those in the lowest ADI quartile (Odds Ratio [OR] 0.84; 95% Confidence Interval [CI], 0.75-0.95) at 90 days following AF diagnosis. In those receiving anticoagulation, individuals in the highest ADI quartile had a 24% lower likelihood of receiving a DOAC prescription as opposed to warfarin prescription than those in the lowest quartile (OR 0.76; 95% CI, 0.60-0.96) at 90 days following AF diagnosis. ConclusionsWe demonstrate the association of higher neighborhood deprivation as determined by ADI with decreased likelihood of (1) anticoagulation prescribing for stroke prevention in AF and (2) prescription of a DOAC when any oral anticoagulation is prescribed. Our results suggest neighborhood-based health inequities in the receipt of anticoagulation prescription for stroke prevention in AF in a large, regional health care system.

Acute illness may increase bleed risk among oral anticoagulant users

In the United States, oral anticoagulant use has increased by 54% since 2012, particularly with the use of newer direct oral anticoagulants (DOACs). Unfortunately, among clinicians in certain settings knowledge gaps persist concerning the safety of these therapies, including the risk of acute infection. A new study published in the BMJ December 21, 2021, suggests that acute respiratory tract infections (RTIs) may increase the rates of major and nonmajor bleeding in patients taking oral anticoagulants. Haroon and colleagues conducted a self-controlled case series that included over 1,200 participants on oral anticoagulant therapy who were exposed to an RTI and had major or non-major bleeding events. The analysis included longitudinal general practice EHR data from the UK’s Clinical Practice Research Datalink with over 3 million validated living patients registered at over 400 practices across the UK. The authors defined a specific “excess bleed risk” time window as a general practice consultation for an RTI for which immediate antibiotics were not prescribed. They then compared bleeding event outcomes within the excess risk window to an observation period in which the patients were unexposed to an RTI, allowing the patients to act as their own controls. This methodology had the advantage of allowing for reliable control of time invariant confounders. The researchers defined the RTI risk window as 90 days from general practice consultation, which was divided into smaller chunks of 0 to 14 days, 15 to 30 days, 30 to 60 days, and 60 to 90 days. The 0- to 14-day window was selected as the primary risk period. Additionally, a “pre-risk” window of 7 days prior to the risk period was established in which bleed events could not be captured as being “unexposed.” This was to compensate for RTI symptom onset before the day of general practice consultation as to not misclassify a bleeding event. To prevent confounding from antibiotic use and subsequent drug–drug interactions with a patient’s oral anticoagulant, a patient remained inside of the 90-day risk window as long as they weren’t prescribed antibiotics. Additionally, in order to control for experienced user bias, the total observation period began on the date of the first new prescription of warfarin or a DOAC. After adjusting for time confounders (e.g., age, calendar year, and season) the authors observed a statistically significant 268% relative increase in the rates of major bleeding—defined as either a GI bleed or an intracranial hemorrhage—in the 0- to 14-day risk window after an RTI consultation compared to the rates within the unexposed period. However, no increase in major bleeding was observed in the other aforementioned risk windows. Additionally, the authors observed a statistically significant 232% increase in the relative rates of clinically relevant non-major bleeding—defined as general practice consultation or hospital admission for haemoptysis, epistaxis, or haematuria—during the 0- to 14-day risk window. Despite 67% of the patients in the analysis being on warfarin, a sensitivity analyses demonstrated that there was little modification in the incidence rates of major and non-major bleeding during the 0- to 14-day risk window when conducting a subgroup analysis based on the specific oral anticoagulant used. A major limitation of this study was the inability for the authors to control or adjust for OTC treatments for RTI. Of particular concern are NSAIDs, which would have the potential to significantly bias the results of major bleeds away from the null given that 87% of the recorded bleed events seen were GI bleeds. The authors stated that they “explored the use of prescribed NSAIDs, but were unable to account for over-the-counter drugs” when discussing the limitations of their study. They went on to say that this confound was significant given that survey data from 1,000 adults in England with a recent RTI indicated that 60% of these patients sought OTC treatments. Other observational studies have shown that acute infection may increase international normalized ratio measure in warfarin users. As it stands, Haroon and colleagues’ study is the only one in the literature that has looked at the effect of acute infection on clinical events within the oral anticoagulant population as a whole. “These findings are important and timely given the increasing rates of oral anticoagulant use and the lack of knowledge and guidance on how to manage oral anticoagulant use during acute infection,” suggested the authors in one of their concluding remarks. “There are potential implications for how patients and clinicians manage oral anticoagulant use during an acute intercurrent illness, but further work is needed before any clinical recommendations are made.”

Safety of direct oral anticoagulants (DOACs) vs. warfarin for people aged ≥ 75 years with atrial fibrillation: a cohort study

Abstract Introduction Warfarin significantly reduces the risk of stroke in people with atrial fibrillation (AF), but historically has been underused in older people due to complicated dosage regimens. DOACs offer an attractive alternative to warfarin and were shown to be non-inferior in randomised controlled trials, however older people were underrepresented in these trials and there have been few studies investigating outcomes specifically in this high risk group (1). Aim To compare the risk of major, non-major, gastrointestinal, and intracranial bleeding between warfarin and DOACs in people aged ≥ 75 years with AF. Methods A cohort of patients aged ≥ 75 years with a diagnosis of AF was extracted from the Clinical Practice Research Datalink (CPRD). Patients could enter the study on the date of their first prescription for warfarin or a DOAC between 1/1/2013 and 27/12/2017. Patients were censored on the date of the outcome, death, or leaving the general practice. Switching between anticoagulants and unexposed periods were measured using prescription mapping. Crude and adjusted hazard rates of the risk of bleeding were calculated using a Cox proportional hazards model with oral anticoagulant prescribing as a time varying covariate. Results The cohort included 10,149 patients in the warfarin group and 10,237 in the DOAC group. The groups had similar characteristics and the average age was 81 in the warfarin group and 82 in the DOAC group. The table summarises the results. Whilst major and non-major bleeding was similar between all DOACs and warfarin, rivaroxaban was associated with higher risk and apixaban lower risk when analysed separately. Risk of gastrointestinal bleeding was higher with all DOACs and rivaroxaban than warfarin but apixaban was not significantly different. Few intracranial events occurred (n=131). Conclusion The results indicate that DOACs as a group are not significantly different to warfarin, however when analysed separately, apixaban may be safer. While the study relies on prescription data and hence it is not known if patients were taking the medications, the large cohort studied is representative of older people who are prescribed these medications in UK primary care. Reference (1) Mitchell A, Watson MC, Welsh T, McGrogan A. Effectiveness and safety of direct oral anticoagulants versus vitamin K antagonists for people aged 75 years and over with atrial fibrillation: A systematic review and meta-analyses of observational studies. Journal of Clinical Medicine. 2019; 8 (554).

Temporal changes in anticoagulant prescribing and atrial fibrillation: results of interrupted time-series analysis of openly available routine data in England

Abstract Introduction The use of anticoagulants for stroke prevention in patients with atrial fibrillation (AF) has been increasing in England in the recent years (1, 2). The changes in practice coincided with several developments in the area of anticoagulants and AF, including: the emergence of evidence supporting anticoagulant use for stroke prevention in AF, changes in guideline recommendations, and the licensing of direct oral anticoagulants (DOACs) as an alternative to warfarin, which was the mainstay of stroke prevention in AF. Currently, there are four DOACs available for use: dabigatran, rivaroxaban, apixaban, and edoxaban. Recent analyses of time trends of anticoagulant prescribing in England showed an increase in DOACs prescribing and a decrease in warfarin prescribing (1, 2). However, more recent exploration of recent anticoagulant prescribing trends is needed. Aim To explore the changes in anticoagulant prescribing for AF in England. Methods Interrupted time-series analysis (ITSA) of openly available data on anticoagulant prescribing and AF. Separate analyses were conducted for data from Sentinel Stroke National Audit Programme (SSNAP) and Quality and Outcomes Framework (QOF). The timeframe of the analysis and the length of time intervals depended on the characteristics of each dataset. Results Analysis of data from SSNAP showed that the proportion of stroke patients who have a diagnosis of AF who were taking an anticoagulant alone prior to admission increased from 32.51% in the third quarter of 2013 to 62.63% in the third quarter of 2020; this coincided with a decreased proportion of stroke patients who have a diagnosis of AF taking antiplatelets alone from 37.10% to 8.31% during the same period. Analysed QOF data on anticoagulants and AF included information about AF prevalence in QOF datasets, the eligibility of patients with AF for anticoagulant based on stroke risk assessment, and the use of anticoagulants among eligible patients. Prevalence of AF in England in QOF datasets increased from 1.52% in 2012/2013 to 2.05% in 2019/2020 (ITSA gradient=0.08, p-value&amp;lt;.001, 95% confidence interval: 0.07- 0.09). The proportion of patients with AF who are considered eligible for anticoagulation per all patients with AF in QOF datasets increased from 44.95% in 2012/2013 to 80.87% in 2019/2020; there was an increase by 25.24% between 2014/2015 and 2015/2016 which corresponds to modifying risk assessment scores to include additional criteria. The proportion of eligible patients with AF being prescribed anticoagulants also increased in the period between 2012/2013 and 2019/2020 (ITSA gradient = 1.98, p-value&amp;lt;.001, 95% confidence interval: 1.52- 2.44). Conclusion The analysis of data from different sources identified an increase in anticoagulant prescribing for patients with AF in England, which is likely to translate into health gains. However, the use of aggregate data in the analysis did not allow for detailed inspection of patient characteristics, and individual anticoagulants were not specified in the datasets. Therefore, quantitative analyses of primary care data of individual anticoagulant prescribing for different patient groups with AF are needed to further understand whether additional improvements are possible in the prevention of complications from atrial fibrillation. References (1) Adderley NJ, Ryan R, Nirantharakumar K, Marshall T. Prevalence and treatment of atrial fibrillation in UK general practice from 2000 to 2016. Heart. 2019;105(1):27-33. (2) Loo SY, Dell’Aniello S, Huiart L, Renoux C. Trends in the prescription of novel oral anticoagulants in UK primary care. British Journal of Clinical Pharmacology. 2017;83(9):2096-106.

Trends and Outcomes of Oral Anticoagulation With Direct Current Cardioversion for Atrial Fibrillation/Flutter at an Academic Medical Center.

BackgroundIncreasing reports suggest the safe use of direct oral anticoagulants (DOACs) in electrical cardioversion. The aim of this study was to assess the trends and 30-day outcomes associated with anticoagulation for cardioversion.MethodsPatients who underwent electrical cardioversion from January 2015 to October 2020 with a 30-day follow-up were included; and outcomes including stroke, transient ischemic attack, intracranial hemorrhage (ICH), and major gastrointestinal bleeding were recorded.ResultsOf the 515 patients, 351 (68%) were men and 164 (32%) were women, with a mean CHA2DS2VASc score of 2.6 ± 1.6. Outpatient apixaban use increased from 10% in 2015 to 46% in 2020 (P < 0.001) with a decline in the use of warfarin from 24% in 2015 to 10% in 2020 (P = 0.023). Apixaban use peri-procedurally for cardioversion increased from 32% in 2015 to 35% in 2020 (P = 0.317), while warfarin use decreased from 23% in 2015 to 14% in 2020 (P = 0.164). At discharge, apixaban prescriptions increased from 21% in 2015 to 61% in 2020 (P < 0.001), while warfarin prescriptions declined from 30% in 2015 to 13% in 2020 (P = 0.009). No ICH was recorded in the 30 days after cardioversion. Ischemic stroke occurred in four (0.7%) patients with one (0.29%) of the 338 patients on a DOAC, one (0.8%) of the 124 patients on warfarin and two (5.5%) of the 36 patients not receiving anticoagulation post cardioversion. There were seven (1%) major gastrointestinal bleeding events in patients on oral anticoagulation, of which four (3%) were on warfarin and three (0.8%) were on DOACs.ConclusionsOur study shows the increasing and safe use of DOACs for the purpose of cardioversion. The rates of 30-day ischemic stroke post cardioversion were low and only occurred in patients admitted in the intensive care unit.