Choice Of Oral Anticoagulants Research Articles

European expert consensus recommendations on the primary care use of direct oral anticoagulants in patients with venous thromboembolism

BackgroundDirect oral anticoagulants for the treatment of venous thromboembolism are supported by robust clinical trial evidence. Despite published guidance, general practitioners are faced with increasingly complex decisions and implementation remains sub-optimal in certain real-world scenarios.MethodsA two stage formal consensus exercise was performed to formulate consensus statements and a summary guide, facilitating optimal management of direct oral anticoagulants in venous thromboembolism patients by generalist physicians across Europe. An online questionnaire distributed to a broad panel (Phase 1), followed by a virtual panel discussion by an expert group (Phase 2) were conducted. Phase 1 statements covered nine management domains, and were developed via a literature review and expert steering committee. Participants rated statements by their level of agreement. Phase 1 responses were collated and analysed prior to discussion and iterative refinement in Phase 2.ResultsIn total 56 participants from across Europe responded to Phase 1. The majority had experience working as general practitioners. Consensus indicated that direct oral anticoagulants are the treatment of choice for managing patients with venous thromboembolism, at initiation and for extended treatment, with a review at three to six months to re-assess treatment effect and risk profile. Direct oral anticoagulant choice should be based on individual patient factors and include shared treatment choice between clinicians and patients; the only sub-group of patients requiring specific guidance are those with cancer.ConclusionResults demonstrate an appreciation of best practices, but highlight challenges in clinical practice. The patient pathway and consensus recommendations provided, aim to highlight key considerations for general practice decision making, and aid optimal venous thromboembolism treatment.

Lower dose direct oral anticoagulation and warfarin in atrial fibrillation. Ischemic stroke, intracranial hemorrhage and mortality in a nationwide registry study

Abstract Background and aims Direct oral anticoagulants (DOACs) have replaced Vitamin-K antagonists as the primary choice of oral anticoagulation (OAC) in atrial fibrillation (AF). However, after several years of experience with DOACs, no studies have been made comparing the efficacy and safety of reduced dose DOACs and warfarin when the quality of warfarin treatment (time in the therapeutic range, TTR) information is available. Methods The Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) is a nationwide study of AF patients combining data from several Finnish healthcare registers. We included all new-onset AF patients from 2011 to 2018 in Finland with purchases of either reduced dose DOAC or warfarin with eligible laboratory data. For patients on warfarin, we calculated TTR percentages and divided patients into TTR quartiles. Occurrence of ischemic stroke (IS), intracranial haemorrhage (ICH), or death during OAC use were recorded as outcomes during a maximum follow-up of 730 days. Crude and weighted rates of IS, ICH and mortality are provided. To minimize confounding by baseline characteristics and concomitant medications, an inverse probability of treatment weighted analysis was applied. Results A total of 52,022 new-onset AF patients with OAC therapy (46.1% male, mean age 75.7 years, 43 548 on warfarin) were followed for 56 382 patient-years (py). The rate of IS among patients was 1.63/100 py for dabigatran (n=2 672), 1.64/100 py for apixaban (n=3 936), 1.49 /100 py for rivaroxaban (n=1 866). For patients with warfarin, the rates of IS in TTR quartiles were 3.45, 1.79, 1.18 and 0.74/100 py from the lowest (mean TTR 32%) to the highest TTR quartile (mean TTR 90%). The weighted rates of IS were 1.34, 0.96 and 1.25/100 py for dabigatran, apixaban and rivaroxaban, and for warfarin from the lowest to the highest quartile: 3.70, 1.87, 1.21 and 0.97/100 py. The rates of ICH were 0.68, 1.09 and 1.06/100 py for dabigatran, apixaban and rivaroxaban, and for warfarin from the lowest to the highest quartile: 3.60, 0.99, 0.51 and 0.32/100 py. The weighted rates of ICH were 0.70, 0.70 and 0.90/100 py for dabigatran, apixaban and rivaroxaban, and for warfarin from the lowest to the highest quartile: 3.80, 1.03, 0.54, 0.34 and 0.97/100 py. For mortality, raw incidences rates were 4.31, 11.40, and 8.11/100 py for for dabigatran, apixaban and rivaroxaban, and for warfarin from the lowest to the highest quartile: 16.45, 5.33, 2.31, and 1.53/100 py. The weighted rates were 3.97, 7.97, and 6.78, for dabigatran, apixaban and rivaroxaban, and for warfarin from the lowest to the highest quartile: 18.08, 5.86, 2.58, and 1.73/100 py. Figures portray cumulative IS incidence and mortality. Conclusion The incidence rates of all three outcomes were highest among patients on warfarin in the lowest TTR quartiles. For reduced dose DOAC patients, weighted IS rates were highest for those on dabigatran, ICH rates for those on rivaroxaban, and mortality rates for those on apixaban.Cumulative Incidence of Ischemic StrokeCumulative mortality

Abstract 17095: Change in Oral Anticoagulant Use for Atrial Fibrillation From 2013 to 2018 Among US Veterans and the Impact of Frailty

Introduction: Direct oral anticoagulants (DOACs) are superior to warfarin in both efficacy and safety regardless of frailty status. Data on prescribing patterns of different oral anticoagulants (OACs) in frail older adults are limited. Methods: We utilized the Veterans Health Administration clinical data, to identify those aged 65 and older with a diagnosis of non-valvular atrial fibrillation (AF) who initiated anticoagulation in 2013 and 2018. Frailty was assessed using the 31-item VA Frailty Index (VA-FI). Patients were stratified into 3 categories. VA-FI: frail (frailty index >0.2), pre-frail (frailty index 0.11-0.2), and non-frail (frailty index 0-0.1). Baseline data on prior stroke, CHA 2 DS 2 -VASc score, and bleeding were extracted. Descriptive statistics and logistic regression were used to examine association of frailty with choice of OAC. Results: Among 39,647 Veterans included from 2013 and 2018, mean age was between 71 to 76. 99% were male and 88% white race. From 2013 to 2018, DOACs use increased from 21% to 88%, while warfarin use decreased accordingly. Among the OACs, dabigatran was dominant (65%) in 2013 but apixaban was dominant (66%) in 2018. Increasing frailty was associated with reduced use of DOACs (p<0.001 in 2013 and 2018). Regardless of the choice of drug, the prior bleeding and prior stroke/transient ischemic attack were mostly seen in the frail population ranging between 54-60% and 20-21% respectively. CHA 2 DS 2 -VASc score averaged 3 for non-frail, and 4 for prefrail and frail patients regardless of the year. (Figure) Conclusion: Prior bleeding and stroke episodes were more common among the frail population. There was significant reduction in use of DOACs in both years with increasing frailty. Studying the impact of anticoagulant choice on clinical outcomes among frail older adults with non-valvular AF are needed.

Comparison of oral anticoagulation by vitamin-K antagonists and non-vitamin-K antagonists for treatment of leaflet thickening after transcatheter aortic valve implantation (TAVI)

IntroductionHypoattenuated leaflet thickening (HALT), as identified by CT imaging, is not infrequent after transcatheter aortic valve implantation (TAVI). The best choice of oral anticoagulation is unknown. We compared the effectiveness of Direct Oral AntiCoagulants (DOAC) and Vitamin-K Antagonists (VKA) to resolve HALT in patients with serial CT aquisitions. MethodsA total of 46 consecutive TAVI patients in whom anticoagulation had been initiated because of HALT and who underwent follow-up CT were identified. Indication and type of anticoagulation was according to physician discretion. Patients on DOAC were compared to VKA therapy regarding resolution of HALT. ResultsMean age of the 46 patients was 80 ± 6 years (59% men), and the mean duration of anticoagulation was 156 days. Overall, 41 patients (89%) showed resolution of HALT with anticoagulation therapy, whereas HALT persisted in 5 patients (11%). Resolution of HALT was seen in 26 out of 30 (87%) patients receiving VKA and in 15 out of 16 (94%) patients receiving DOAC, respectively. Groups did not differ regarding age, cardiovascular risk factors, TAVI prosthesis type and size or duration of anticoagulation (all p > 0.05). ConclusionAnticoagulation therapy resolves leaflet thickening after TAVI in most patients. Non-Vitamin-K antagonists seem to be an effective alternative to Vitamin-K antagonists. This finding needs to be confirmed in larger prospective trials.

Identifying treatment heterogeneity in atrial fibrillation using a novel causal machine learning method

Lifelong oral anticoagulation is recommended in patients with atrial fibrillation (AF) to prevent stroke. Over the last decade, multiple new oral anticoagulants (OACs) have expanded the number of treatment options for these patients. While population-level effectiveness of OACs has been compared, it is unclear if there is variability in benefit and risk across patient subgroups. We analyzed claims and medical data for 34,569 patients who initiated a nonvitamin K antagonist oral anticoagulant (non-vitamin K antagonist oral anticoagulant (NOAC); apixaban, dabigatran, and rivaroxaban) or warfarin for nonvalvular AF between 08/01/2010 and 11/29/2017 from the OptumLabs Data Warehouse. A machine learning (ML) method was applied to match different OAC groups on several baseline variables including, age, sex, race, renal function, and CHA2DS2 -VASC score. A causal ML method was then used to discover patient subgroups characterizing the head-to-head treatment effects of the OACs on a primary composite outcome of ischemic stroke, intracranial hemorrhage, and all-cause mortality. The mean age, number of females and white race in the entire cohort of 34,569 patients were 71.2 (SD, 10.7) years, 14,916 (43.1%), and 25,051 (72.5%) respectively. During a mean follow-up of 8.3 (SD, 9.0) months, 2,110 (6.1%) of patients experienced the composite outcome, of whom 1,675 (4.8%) died. The causal ML method identified 5 subgroups with variables favoring apixaban over dabigatran; 2 subgroups favoring apixaban over rivaroxaban; 1 subgroup favoring dabigatran over rivaroxaban; and 1 subgroup favoring rivaroxaban over dabigatran in terms of risk reduction of the primary endpoint. No subgroup favored warfarin and most dabigatran vs warfarin users favored neither drug. The variables that most influenced favoring one subgroup over another included Age, history of ischemic stroke, thromboembolism, estimated glomerular filtration rate, Race, and myocardial infarction. Among patients with AF treated with a NOAC or warfarin, a causal ML method identified patient subgroups with differences in outcomes associated with OAC use. The findings suggest that the effects of OACs are heterogeneous across subgroups of AF patients, which could help personalize the choice of OAC. Future prospective studies are needed to better understand the clinical impact of the subgroups with respect to OAC selection.

Abstract P625: Differences in Urban/Rural Oral Anticoagulation and Mortality Among People With Incident Venous Thromboembolism: Medicare 20% Sample 2016-2018

Introduction: Oral anticoagulants (OAC) are a standard and highly efficacious treatment for venous thromboembolism (VTE), with newer direct oral anticoagulants (DOACs; rivaroxaban and apixaban) equivalent or preferred over warfarin for many patients. Rural residents often lack easy access to medical care, which may cause differences in OAC use and outcomes in people with incident VTE. Hypothesis: People enrolled in Medicare who reside in rural locations will be less likely to be prescribed DOACs for primary treatment of incident VTE and will experience higher 6-month mortality compared to patients residing in urban areas. Methods: We used the Medicare 20% sample to identify a cohort of individuals aged ≥65 years with incident VTE and prescribed an OAC from 2016-2018. Risk factors, demographics, and ZIP codes to create urban/rural categories based on rural-urban commuting area codes were defined at time of VTE diagnosis. All-cause mortality and death date were ascertained via Medicare linkage to the Social Security Administration. Cox regression estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association of urban/rural status and 6-month mortality rates, adjusting for demographics, comorbidities and medications. Urban/rural status and OAC choice were tested for multiplicative interaction. Results: Among 37,954 beneficiaries with VTE (mean age 76.7, SD 8.1), 82% were urban and 18% were rural. There were 3,778 deaths within 6 months of VTE diagnosis; 3,130 among urban residents while 649 among rural residents (83% vs. 17%). Overall, warfarin was prescribed more often in rural areas than urban areas (34% vs. 27%), rivaroxaban prescriptions were less common in rural versus urban areas (32% vs. 36%), and apixaban did not differ by rural versus urban status (35% vs. 37%). In multivariable-adjusted analyses, risk of mortality was not significantly different in rural versus urban areas (HR: 1.08 (0.99-1.17)). The HRs for mortality with rivaroxaban versus warfarin was 0.85 (95% CI: 0.79, 0.93), for apixaban versus warfarin it was 0.96 (95% CI: 0.89, 1.04), while for apixaban versus rivaroxaban it was 1.14 (95% CI: 1.05, 1.23). There was no interaction between OAC prescribed and urban/rural status for all comparisons of OACs (p-interaction rivaroxaban vs. warfarin: 0.50; apixaban vs. warfarin: 0.54; apixaban vs. rivaroxaban: 0.27). Conclusions: Rural versus urban residence resulted in less prescription of DOACs versus warfarin or oral anticoagulation treatment of VTE, but not a significant difference in 6-month mortality. The reasons for different prescribing patterns are unclear, whether due to comorbid conditions or provider knowledge. Greater attention to understanding rural-urban treatment differences is needed to ensure high quality care for everyone.

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.

Abstract 14098: Early Recurrence Following Resolution of a Watchman Device Related Thrombus

Introduction: Left atrial appendage occlusion devices are widely used as stroke prevention alternative to oral anticoagulation in patients with atrial fibrillation (AF). Recently, there has been growing concern for device related thrombus (DRT) and the associated risk for stroke and systemic embolism. Studies have mentioned the incidence, predictors, and risk factors for DRT post left atrial appendage occlusion devices. However, not much is known about DRT recurrence, and reports describing such events despite anticoagulation are very limited. Methods: This report describes early DRT recurrence post WATCHMAN implantation following initial treatment to resolution of DRT with anticoagulation. Results: A 79-year-old woman with permanent atrial fibrillation and no identifiable risk factors for DRT, underwent WATCHMAN implantation . TEE at 45 days showed a well-seated WATCHMAN device with no peri-device leak but revealed a DRT on the surface of the device, confirmed by CT angiography. Patient was prescribed Eliquis for 3 months and aspirin 325 mg daily was continued. Complete resolution of DRT was noted on a repeat CT scan 3 months later and Eliquis was discontinued. She returned approximately 1 months later (and few weeks after completing her 3-month course of Eliquis) for a repeat TEE, which now revealed a new recurrent DRT. Conclusions: This report adds to the current literature about early DRT recurrence and possible emphasis on continued anticoagulation following first DRT to prevent recurrence. Although several risk factors have been identified to predict DRT, it is unclear which patients are at increased risk for recurrence of DRT. Patient and procedural factors and the choice of oral anticoagulation seem to play a role. Figure 1: Appearance of device related thrombus on cardiac computed tomography (CT). Illustration of a hypo attenuated thickening on the surface of the left atrial appendage occlusion device suggestive of device related thrombus.

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).

A personalised approach to the choice of oral anticoagulants in elderly and senile patients with atrial fibrillation

Introduction. In recent years, data have been accumulated regarding possible associations between cognitive impairment and atrial fibrillation. The results of retrospective and prospective studies confirm that anticoagulant therapy in patients with AF can reduce the risk of cognitive impairment and dementia.Objective. To study the individual characteristics of elderly and senile patients with atrial fibrillation, influencing the choice of anticoagulant therapy, with a view to its subsequent optimization.Materials and methods. The study included 159 patients with atrial fibrillation of non-valvular genesis aged over 60 years. 4 groups of patients were formed. The largest number of patients received rivaroxaban and warfarin (36.4% and 34.6%, respectively). 26 (16.3%) patients were treated with dabigatran, 20 (12.6%) patients with apixaban. The risk of thromboembolic complications was assessed on the CHA2DS2-VASc scale. The HAS-BLED scale was used to assess the risk of bleeding. A pharmacogenetic study (carriage of polymorphic alleles of the CYP2C9 and VCORC1 genes) was conducted in 138 patients. Cognitive impairment was assessed by a Mini-Cog test and a battery of frontal tests.Results. Taking oral anticoagulants reduces the risk of stroke and dementia in patients; the presence of cognitive impairment, in turn, significantly reduces the patient’s adherence to therapy and reduces the effectiveness of therapy. Patients’ adherence to therapy was significantly lower by 10–20% in patients with cognitive impairment according to the Mini-Cog test and a battery of frontal tests. In the absence of pronounced cognitive impairment (higher adherence to treatment) and availability and willingness to control INR, warfarin remains the drug of choice in patients with renal insufficiency.Conclusions. A number of problems with the use of oral anticoagulants in elderly patients with atrial fibrillation have been identified. The ease of use of new oral anticoagulants, the absence of the need to select doses and monitor therapy is an important factor when choosing a drug.

Preferences for and use of oral anticoagulants for stroke prevention in atrial fibrillation under real-world conditions in Germany: A survey among physicians

In Germany, there is little real-world evidence on physicians’ choice of oral anticoagulants (OACs). Our study aimed at assessing preferences for and prescribing patterns of treatment options for stroke prevention in atrial fibrillation in clinical practice in Germany.We conducted a nationwide quantitative online survey among office-based physicians in Germany. Physicians were asked about their preference for and use of treatment options as well as factors influencing their choice of a specific OAC.A total of n = 953 physicians was surveyed in September and October 2020 (general physicians: 36.0%; internists: 37.3%; cardiologists: 23.7%; neurologists: 10.5%; multiple specialties possible). Preference and use were highest for non-vitamin K oral anticoagulants (NOACs); followed by vitamin K antagonists (VKAs). Most preferred OACs were apixaban (39.3%), rivaroxaban (28.5%) and edoxaban (14.7%). Most used OACs were apixaban (24.3%), rivaroxaban (21.2%) and phenprocoumon (21.4%). NOACs were preferred more often than used (85.6% > 68.6%). VKAs were preferred less often than used (9.6% < 23.5%). OAC attributes and patient characteristics related to efficacy and safety, as well as patients’ kidney function were most important when selecting a specific OAC. Federal and regional governance instruments likely influenced treatment decision-making.We found a high divergence between preferences for and use of available treatment options in clinical practice. Further exploration of the importance of OAC attributes, patient characteristics as well as federal and regional governance instruments for physicians’ choice of a specific OAC may help to further optimize the healthcare of patients with atrial fibrillation in the long-term.

Aspects of anticoagulant therapy in venous thromboembolism, pulmonary embolism. Focus on elderly patients

The prevalence and mortality due to venous thromboembolism (VTE) occupies a leading position among the population throughout the world. The incidence and severity of VTE increases the older the patient. The emergence of a new group of direct oral anticoagulants significant changed the management of these groups of patients. The article touches upon the problem of choice, efficacy and safety of oral anticoagulants in elderly and senile patients with VTE, in particular in pulmonary embolism (PE). An analysis of randomized clinical trials and prospective cohort studies is given. In addition, rational recommendations are given on the optimal choice of oral anticoagulant in these categories of patients. Apixaban and rivaroxaban are highly effective drugs of choice with a reliable safety profile in patients of the senile age group in the prevention and treatment of VTE, including PE, and apixaban has the most optimal profile and safety class among all other oral anticoagulants when used in elderly and senile patients.

Pocket hematoma after pacemaker or defibrillator surgery: Direct oral anticoagulants versus vitamin K antagonists.

BackgroundDirect oral anticoagulants (DOACs) are the preferred choice of oral anticoagulation in patients with atrial fibrillation (AF). Randomized trials have demonstrated the efficacy and safety of DOAC in patients undergoing a cardiac implantable electronic device procedure (CIED); however, there is limited real-world data.ObjectiveTo evaluate the outcome of patients undergoing an elective CIED procedure in a tertiary referral center with an interrupted DOAC or continued vitamin K antagonist (VKA) regimen.MethodsThis was a retrospective single-center study of consecutive patients with AF undergoing an elective CIED procedure between January 2016 and June 2019. The primary endpoint was a clinically significant pocket hematoma < 30 days after surgery. The secondary endpoint was any systemic thromboembolic complication < 30 days after surgery.ResultsOf a total of 1,033 elective CIED procedures, 283 procedures were performed in patients with AF using oral anticoagulation. One-third of the procedures were performed under DOAC (N = 81, 29%) and the remainder under VKA (N = 202, 71%). The DOAC group was younger, had less chronic renal disease, more paroxysmal AF and a lower HAS-BLED score. The VKA group more often underwent a generator change only in comparison to the DOAC group. Clinically significant pocket hematoma occurred in 5 patients (2.5%) in the VKA group and did not occur in the DOAC group (P = 0.33). There were no thromboembolic events reported.ConclusionIn patients with AF undergoing an elective CIED procedure, the risk of a pocket hematoma and a systemic thromboembolic event is comparably low when using either continued VKA or interrupted DOAC.

Frailty and Clinical Outcomes of Direct Oral Anticoagulants Versus Warfarin in Older Adults With Atrial Fibrillation : A Cohort Study.

The role of differing levels of frailty in the choice of oral anticoagulants for older adults with atrial fibrillation (AF) is unclear. To examine the outcomes of direct oral anticoagulants (DOACs) versus warfarin by frailty levels. 1:1 propensity score-matched analysis of Medicare data, 2010 to 2017. Community. Medicare beneficiaries with AF who initiated use of dabigatran, rivaroxaban, apixaban, or warfarin. Composite end point of death, ischemic stroke, or major bleeding by frailty levels, defined by a claims-based frailty index. In the dabigatran-warfarin cohort (n= 158730; median follow-up, 72 days), the event rate per 1000 person-years was 63.5 for dabigatran initiators and 65.6 for warfarin initiators (hazard ratio [HR], 0.98 [95% CI, 0.92 to 1.05]; rate difference [RD], -2.2 [CI, -6.5 to 2.1]). For nonfrail, prefrail, and frail persons, HRs were 0.81 (CI, 0.68 to 0.97), 0.98 (CI, 0.90 to 1.08), and 1.09 (CI, 0.96 to 1.23), respectively. In the rivaroxaban-warfarin cohort (n= 275944; median follow-up, 82 days), the event rate per 1000 person-years was 77.8 for rivaroxaban initiators and 83.7 for warfarin initiators (HR, 0.98 [CI, 0.94 to 1.02]; RD, -5.9 [CI, -9.4 to -2.4]). For nonfrail, prefrail, and frail persons, HRs were 0.88 (CI, 0.77 to 0.99), 1.04 (CI, 0.98 to 1.10), and 0.96 (CI, 0.89 to 1.04), respectively. In the apixaban-warfarin cohort (n= 218738; median follow-up, 84 days), the event rate per 1000 person-years was 60.1 for apixaban initiators and 92.3 for warfarin initiators (HR, 0.68 [CI, 0.65 to 0.72]; RD, -32.2 [CI, -36.1 to -28.3]). For nonfrail, prefrail, and frail persons, HRs were 0.61 (CI, 0.52 to 0.71), 0.66 (CI, 0.61 to 0.70), and 0.73 (CI, 0.67 to 0.80), respectively. Residual confounding and lack of clinical frailty assessment. For older adults with AF, apixaban was associated with lower rates of adverse events across all frailty levels. Dabigatran and rivaroxaban were associated with lower event rates only among nonfrail patients. National Institute on Aging.

Abstract P143: Effects Of Oral Anticoagulant Choice On Mortality In The Primary Treatment Of Non-cancer Venous Thromboembolism: Medicare, 2011-2016

Introduction: Oral anticoagulants (OAC) are the mainstay of venous thromboembolism (VTE) treatment, with newer direct oral anticoagulants (DOACs; rivaroxaban, apixaban, and dabigatran) approved for the treatment of VTE. Although clinical trials have evaluated DOACs versus warfarin individually, there are few direct comparisons of OAC treatment choice among VTE patients and risk of mortality. Hypothesis: Patients enrolled in Medicare who are prescribed DOACs for primary treatment of incident VTE will experience a lower rate of mortality compared to patients prescribed warfarin. Among different DOACs, there will be no difference in rate of mortality. Methods: We used the Medicare 20% sample to identify a cohort of 84,877 individuals with incident VTE from 2011-2016. We excluded VTE patients with evidence of prevalent cancer (N=27,603). Beneficiaries were then matched by OAC using patient characteristics at date of VTE diagnosis to create an analytic dataset of 35,922. All-cause mortality and date of death were ascertained from linkage with the National Death Index. We used Cox regression to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CIs) for the association of OAC choice with mortality. All analyses were limited to 6-months of follow-up. Multiplicative interaction by age (≥75 years), sex, race and kidney disease were explored. Results: In our matched sample 21,320 individuals were prescribed warfarin, 10,504 rivaroxaban and 3,681 apixaban. The average age was 77 years (SD: 8 years), 63% were female, 82.0% were white, 10.4% black and 7.6% were other/unknown. There were 2,701 deaths within 6 months of VTE diagnosis, of which 1,726 were warfarin, 604 were rivaroxaban, and 272 were apixaban. In the adjusted models, individuals prescribed rivaroxaban had 0.85 times the rate of 6-month all-cause mortality compared to those prescribed warfarin (HR: 0.85; 95% CI: 0.77, 0.93). There was no difference in mortality rates comparing apixaban to warfarin (HR: 0.98; 95% CI: 0.85, 1.13) or apixaban to rivaroxaban (HR: 1.12; 95% CI: 0.95, 1.32). For the interaction analyses among those aged under 75, apixaban users had a higher risk of mortality compared to warfarin (HR: 1.37; 95% CI: 1.06, 1.77) and rivaroxaban users (HR: 1.32; 95% CI: 0.99, 1.77). No other interactions were observed. Conclusions: We found differences in mortality related to anticoagulation choice for the treatment of VTE, with rivaroxaban having a lower mortality risk than warfarin and a similar risk overall with apixaban. However, apixaban had a higher risk of mortality in secondary analyses stratified by age, with a higher risk in those &lt;75. The age-dependent association of apixaban with mortality was not hypothesized and requires further confirmation.

Impact of oral anticoagulant choice for the secondary prevention of venous thromboembolism on the risk of inpatient bleeding

BackgroundRandomized trials suggest that direct oral anticoagulants (DOACs) are at least as effective as warfarin for primary treatment of VTE and that bleeding risk may be lower for some DOACs relative to warfarin. However, there is very little information regarding potential bleeding risks for DOACs versus warfarin in secondary prevention of VTE. ObjectiveThe aim of this study was to compare rates of bleeding events resulting in inpatient admissions between individuals taking apixaban, rivaroxaban, and warfarin for secondary prevention of VTE during the period 2013‐2017. MethodsWe used the IBM MarketScan Commercial Claims and Encounters Database and Medicare Supplemental and Coordination of Benefits Database (IBM Watson Health, Ann Arbor, MI) to establish a retrospective cohort. Initial venous thrombolism events were defined from medical claims, and follow‐up for this cohort began 6 months after the initial event. Bleeding events resulting in inpatient admission were identified from claims data over the subsequent year of secondary prevention. ResultsA total of 69 264 individuals were identified for the cohort, with 567 bleeding events. The crude rate of bleeding was highest among warfarin users (1.47/100 person‐years; 95% confidence interval [CI], 1.24‐1.74) and lower among those on either apixaban (1.00/100 person‐years; 95% CI, 0.65‐1.54) or rivaroxaban (0.84/100 person‐years; 95% CI, 0.66‐1.08). In multivariable adjusted Cox models, those on apixaban (hazard ratio [HR], 0.80; 95% CI, 0.50‐1.29) and rivaroxaban (HR, 0.81; 95% CI, 0.59‐1.09) had somewhat lower rates of bleeding events relative to those on warfarin. ConclusionsWe found modest evidence of decreased risk of bleeding for apixaban and rivaroxaban. These estimates were relatively imprecise.

Direct-Acting Oral Anticoagulant Choice for Stroke Prevention in Obese Patients With Atrial Fibrillation

Anticoagulation with direct-acting oral anticoagulants (DOACs) is recommended over warfarin for stroke prevention in patients with atrial fibrillation (AF). The efficacy of DOACs over warfarin in obese patients with AF is less defined and may carry the potential for subtherapeutic anticoagulation and reduced efficacy. The best available evidence to guide DOAC use in obese patients with AF is from analysis of obese subgroups of all the major landmark DOAC trials. From these subgroup analyses of the RE-LY, ARISTOTLE, ENGAGE-AF TIMI 48, and ROCKET-AF trials, DOAC use in obese patients demonstrated efficacy similar or superior to warfarin for stroke reduction. Major bleeding rates were similar or higher with DOACs compared with warfarin in these obese subgroup analyses. Meta-analysis of the above major clinical trials concluded that DOACs were more effective compared with warfarin for stroke prevention in obese patients (up to a body mass index [BMI] of 50 kg/m2) and had lower incidence of major bleeding. The totality of evidence supports that DOACs are as effective, if not superior, to warfarin in obese patients with AF. We propose an algorithm, based on the available evidence and current guidelines, to guide the use of DOACs based on severity of obesity. Any DOAC can be used in obese patients with BMI < 40 kg/m2. In patients with a BMI of 40-50 kg/m2, warfarin should be used, but apixaban or edoxaban can be considered. In obese patients with a BMI > 50 kg/m2, warfarin should be used.

Efficacy and safety of direct oral anticoagulants in patients undergoing elective electrical cardioversion: A real-world patient population

BackgroundDirect oral anticoagulants (DOACs) have emerged as the preferred choice of oral anticoagulation in patients with atrial fibrillation. Randomized trials have demonstrated the efficacy and safety of DOAC in patients undergoing electrical cardioversion (ECV); however, there is limited real-world data. ObjectiveTo evaluate the outcome of patients undergoing an elective ECV for atrial tachyarrhythmia in a tertiary referral center who were treated with DOAC or vitamin K antagonist (VKA) without routine trans esophageal echocardiography (TEE). MethodsThis was a retrospective single-center cohort study of consecutive patients undergoing an elective ECV for atrial tachyarrhythmia from January 2013 to February 2020. The primary endpoints were thromboembolism (composite of stroke, transient ischemic attack or systemic embolism) and major bleeding events within 60 days. ResultsA total of 1431 ECV procedures were performed in 920 patients. One-third of the procedures were performed under DOAC (N = 488, 34%) and the remainder of the procedures was performed under VKA (N = 943, 66%). There were no differences between groups with regard to demographic variables (mean age 62.4 ± 11.7, 72% men) and mean CHA2DS2-VASc score (2.3 ± 1.6); however, the VKA group had a higher proportion of patients with co-morbidity. Thromboembolism occurred in 0.41% in the DOAC group versus 0.64% in the VKA group (P = 0.72). Major bleeding events occurred in 0.41% in the DOAC group versus 0.11% in the VKA group (P = 0.27). ConclusionIn a real-world population, the rates of thromboembolism and major bleeding events were low after elective ECV in patients using DOAC or VKA, even without routine TEE.

Anticoagulation in Italian patients with venous thromboembolism and thrombophilic alterations: findings from START2 register study.

Randomised control trials have assessed the efficacy and safety of direct oral anticoagulants in the prophylaxis and treatment of venous thromboembolism (VTE). Positive but limited results have been reported in patients with inherited thrombophilia. Using an Italian, multicentre, prospective registry of consecutive patients presenting with symptomatic, acute VTE, we aimed to assess which factors are involved in making the choice of the drug that best fits the patient's risk profile in a large real-world setting of VTE patients. We investigated 4,866 VTE patients who took oral anticoagulants in the period between 2012 and April 2018 to prevent a new thromboembolic episode. The large majority of patients who underwent thrombophilic screening, regardless of the results obtained, were prescribed direct oral anticoagulants rather than conventional anticoagulant therapy (p<0.001). During anticoagulation, bleeding events occurred more frequently in patients on conventional anticoagulant therapy (4.2%) than in those receiving direct oral anticoagulants (1.8%) and an increase in bleeding events was observed in patients who tested positive at the thrombophilic screening. Overall, a higher number of recurrent VTE was observed in patients not screened for thrombophilia (n=36; 1.7%) than in those screened (n=20; 0.7%; adjusted odds ratio: 2.2; 95% confidence interval: 1.2-4.1). The present data confirm previous findings from other post-marketing registries and suggest that the choice of oral anticoagulation is strongly driven by patients' characteristics and VTE manifestations. Factors leading to the prescription of thrombophilic screening may identify a patient with a lower risk of VTE recurrence during anticoagulation.

Dabigatran, the oral anticoagulant of choice at discharge in patients with non-valvular atrial fibrillation and COVID-19 infection: the ANIBAL* protocol

Atrial fibrillation is a frequent complication among patients with severe coronavirus disease-2019 (COVID-19) infection. Both direct and indirect mechanisms through COVID-19 have been described to explain this relationship. COVID-19 infection increases the risk of developing both arterial and venous thrombotic complications through systemic coagulation activation, leading to increased mortality. Chronic oral anticoagulation is essential to reduce the thromboembolic risk among AF patients. Switching to low-molecular-weight heparin has been recommended during hospitalization for COVID-19 infection. Of note, at discharge, the prescription of direct oral anticoagulants may offer some advantages over vitamin K antagonists. However, oral anticoagulants should only be prescribed after the consideration of drug–drug interactions with antiviral therapies as well as of the risk of hepatotoxicity, which is common among individuals with severe COVID-19 pneumonia. Not all anticoagulants have the same risk of hepatotoxicity; dabigatran has shown a good efficacy and safety profile and could have a lower risk of hepatotoxicity. Furthermore, its metabolism by cytochrome P450 is absent and it has a specific reversal agent. Therefore, dabigatran may be considered as a first-line choice for oral anticoagulation at discharge after COVID-19 infection. In this review, the available information on the antithrombotic management of AF patients at discharge after COVID-19 infection is updated. In addition, a practical algorithm, considering renal and liver function, which facilitates the anticoagulation choice at discharge is presented.