scholarly journals Risks and Benefits of Direct Oral Anticoagulants across the Spectrum of GFR among Incident and Prevalent Patients with Atrial Fibrillation

2018 ◽  
Vol 13 (8) ◽  
pp. 1144-1152 ◽  
Author(s):  
Jung-Im Shin ◽  
Alex Secora ◽  
G. Caleb Alexander ◽  
Lesley A. Inker ◽  
Josef Coresh ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Oral Anticoagulant ◽  
Proportional Hazards ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Cox Proportional Hazards ◽  
Direct Oral Anticoagulant ◽  
Bleeding Events ◽  
Risk Of Bleeding

Background and objectivesAll randomized trials of direct oral anticoagulants in atrial fibrillation excluded patients with severe kidney disease. The safety and effectiveness of direct oral anticoagulants across the range of eGFR in real-world settings is unknown. Our objective is to quantify the risk of bleeding and benefit of ischemic stroke prevention for direct oral anticoagulants compared with warfarin in patients with atrial fibrillation with and without CKD.Design, setting, participants, & measurementsWe created a propensity score–matched cohort of 3206 patients with atrial fibrillation and direct oral anticoagulant use and 3206 patients with atrial fibrillation using warfarin from October of 2010 to February of 2017 in an electronic health record (Geisinger Health System). The risks of bleeding and ischemic stroke were compared between direct oral anticoagulant and warfarin users using Cox proportional hazards regression, stratified by eGFR (≥60 and <60 ml/min per 1.73 m2).ResultsThe mean (SD) age of the 6412 participants was 72 (12) years, 47% were women, and average eGFR was 69 (21) ml/min per 1.73 m2. There were 1181 bleeding events and 466 ischemic strokes over 7391 person-years of follow-up. Compared with warfarin use, the hazard ratios (HRs) (95% confidence interval [95% CI]) of bleeding associated with direct oral anticoagulant use were 1.01 (0.88 to 1.17) and 1.23 (1.02 to 1.48) for those with eGFR≥60 and eGFR<60 ml/min per 1.73 m2, respectively (P-interaction=0.10). There was no difference between direct oral anticoagulant and warfarin users in the risk of ischemic stroke: HRs (95% CI) of 0.94 (0.74 to 1.18) and 1.02 (0.76 to 1.37) for those with eGFR≥60 and eGFR<60 ml/min per 1.73 m2, respectively (P-interaction=0.70). Similar findings were observed with individual drugs.ConclusionsIn a large health care system, patients with eGFR<60 ml/min per 1.73 m2 who took direct oral anticoagulants for atrial fibrillation had slightly higher risk of bleeding compared with those on warfarin, but similar benefits from prevention of ischemic stroke.

Oral Anticoagulants in Atrial Fibrillation Patients With Recent Stroke Who Are Dependent on the Daily Help of Others

Stroke ◽  
2021 ◽  
Author(s):  
Louisa Meya ◽  
Alexandros A. Polymeris ◽  
Sabine Schaedelin ◽  
Fabian Schaub ◽  
Valerian L. Altersberger ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Proportional Hazards ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Cox Proportional Hazards ◽  
Composite Outcome ◽  
Unique Identifier ◽  
The Individual

Background and Purpose: Data on the effectiveness and safety of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) in patients with stroke attributable to atrial fibrillation (AF) who were dependent on the daily help of others at hospital discharge are scarce. Methods: Based on prospectively obtained data from the observational Novel-Oral-Anticoagulants-in-Ischemic-Stroke-Patients-longterm registry from Basel, Switzerland, we compared the occurrence of the primary outcome—the composite of recurrent ischemic stroke, major bleeding, and all-cause death—among consecutive patients with AF-stroke treated with either VKAs or DOACs between patients dependent (defined as modified Rankin Scale score, 3–5) and patients independent at discharge. We used simple, adjusted, and weighted Cox proportional hazards regression to account for potential confounders. Results: We analyzed 801 patients (median age 80 years, 46% female), of whom 391 (49%) were dependent at discharge and 680 (85%) received DOACs. Over a total follow-up of 1216 patient-years, DOAC- compared to VKA-treated patients had a lower hazard for the composite outcome (hazard ratio [HR], 0.58 [95% CI, 0.42–0.81]), as did independent compared to dependent patients (HR, 0.54 [95% CI, 0.40–0.71]). There was no evidence that the effect of anticoagulant type (DOAC versus VKA) on the hazard for the composite outcome differed between dependent (HR dependent , 0.68 [95% CI, 0.45–1.01]) and independent patients (HR independent , 0.44 [95% CI, 0.26–0.75]) in the simple model ( P interaction =0.212). Adjusted (HR dependent , 0.74 [95% CI, 0.49–1.11] and HR independent , 0.51 [95% CI, 0.30–0.87]; P interaction =0.284) and weighted models (HR dependent , 0.79 [95% CI, 0.48–1.31] and HR independent , 0.46 [95% CI, 0.26–0.81]; P interaction =0.163) yielded concordant results. Secondary analyses focusing on the individual components of the composite outcome were consistent to the primary analyses. Conclusions: The benefits of DOACs in patients with atrial fibrillation with a recent stroke were maintained among patients who were dependent on the help of others at discharge. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03826927.

Abstract MP13: Comparative Effectiveness of Direct Oral Anticoagulants and Warfarin on Risk of Bleeding Resulting in Hospitalization Among Venous Thromboembolism Patients

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Pamela L Lutsey ◽  
Neil A Zakai ◽  
Richard F MacLehose ◽  
Faye L Norby ◽  
Rob F Walker ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Comparative Effectiveness ◽  
Proportional Hazards ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Final Analysis ◽  
Bleeding Risk ◽  
Cox Proportional Hazards ◽  
Bleeding Events ◽  
Risk Of Bleeding

Background: Direct oral anticoagulants (DOACs), including rivaroxaban, dabigatran, apixaban and edoxaban, have been approved as alternatives to warfarin for the primary treatment of venous thromboembolism (VTE). However, understanding of their comparative effectiveness in practice-based populations is limited. Objective: Among anticoagulant-naïve VTE patients, estimate the association of type of oral anticoagulant (OAC) with the rate of bleeding resulting in hospitalization. Methods: Patients with VTE and prescription for an OAC were identified from the US Truven Health MarketScan® Commercial and Medicare Supplemental databases for the period from 2011-2015. Hospitalization related to bleeding events (inclusive of intracranial, gastrointestinal and other) was defined using a validated algorithm. In head-to-head comparisons, initiators of a specific OAC were matched with up to 5 initiators of the comparing OAC by age, sex, and time since database enrollment. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (95%CI) for bleeding by OAC, adjusted for age, sex, and a comorbidity propensity score (created using prevalence of 20 common diagnoses and procedures). Results: The final analysis included 83,831 VTE patients who were 49.9% female and on average (standard deviation) 59.0 (16.0) years old. Of these, the initial OAC prescribed for 2,604 was apixaban, for 1,669 dabigatran, for 28,518 rivaroxaban, and for 48,514 warfarin. A total of 1,947 bleeding events occurred over an average of 13 months. Compared to new warfarin users, risk of bleeding was lower among patients initiating apixaban [HR (95%CI): 0.55 (0.36, 0.83)] and rivaroxaban [0.80 (0.72, 0.89)], but similar among new dabigatran users [0.96 (0.72, 1.27)]. In head-to-head DOAC comparisons, relative to rivaroxaban, risk of bleeding was lower among users of apixaban [0.57 (0.36, 0.89)] but similar for users of dabigatran [1.05 (0.73, 1.51)]. Due to low numbers we did not conduct analyses of edoxaban or a head-to-head comparison of dabigatran versus apixaban. Conclusion: In this practice-based population of 83,831 patients prescribed OACs for the treatment of VTE, subsequent risk of hospitalized bleeding was lowest among those prescribed apixaban, intermediate among those prescribed rivaroxaban, and highest among those prescribed warfarin and dabigatran. These data demonstrate that differences in bleeding risk exist by DOAC. While risk factors for bleeding might impact choice of warfarin versus the DOACs, the choice between DOACs may be less likely to be based on patient conditions.

scholarly journals Comparative clinical outcomes between direct oral anticoagulants and warfarin among elderly patients with non-valvular atrial fibrillation in the CMS medicare population

2019 ◽  
Vol 48 (2) ◽  
pp. 240-249 ◽  
Author(s):  
Alpesh Amin ◽  
Allison Keshishian ◽  
Oluwaseyi Dina ◽  
Amol Dhamane ◽  
Anagha Nadkarni ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Lower Risk ◽  
Proportional Hazards ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Cox Proportional Hazards ◽  
Cardiac Events ◽  
Cox Proportional Hazards Models ◽  
Medicare Patients ◽  
Similar Risk

AbstractAtrial fibrillation (AF) prevalence increases with age; > 80% of US adults with AF are aged ≥ 65 years. Compare the risk of stroke/systemic embolism (SE), major bleeding (MB), net clinical outcome (NCO), and major adverse cardiac events (MACE) among elderly non-valvular AF (NVAF) Medicare patients prescribed direct oral anticoagulants (DOACs) vs warfarin. NVAF patients aged ≥ 65 years who initiated DOACs (apixaban, dabigatran, and rivaroxaban) or warfarin were selected from 01JAN2013-31DEC2015 in CMS Medicare data. Propensity score matching was used to balance DOAC and warfarin cohorts. Cox proportional hazards models estimated the risk of stroke/SE, MB, NCO, and MACE. 37,525 apixaban–warfarin, 18,131 dabigatran–warfarin, and 55,359 rivaroxaban–warfarin pairs were included. Compared to warfarin, apixaban (HR: 0.69; 95% CI 0.59–0.81) and rivaroxaban (HR: 0.82; 95% CI 0.73–0.91) had lower risk of stroke/SE, and dabigatran (HR: 0.88; 95% CI 0.72–1.07) had similar risk of stroke/SE. Apixaban (MB: HR: 0.61; 95% CI 0.57–0.67; NCO: HR: 0.64; 95% CI 0.60–0.69) and dabigatran (MB: HR: 0.79; 95% CI 0.71–0.89; NCO: HR: 0.84; 95% CI 0.76–0.93) had lower risk of MB and NCO, and rivaroxaban had higher risk of MB (HR: 1.08; 95% CI 1.02–1.14) and similar risk of NCO (HR: 1.04; 95% CI 0.99–1.09). Compared to warfarin, apixaban had a lower risk for stroke/SE, MB, and NCO; dabigatran had a lower risk of MB and NCO; and rivaroxaban had a lower risk of stroke/SE but higher risk of MB. All DOACs had lower risk of MACE compared to warfarin.

Personalized approach for direct oral anticoagulant prescription: from theory to practice

2019 ◽  
Vol 91 (7) ◽  
pp. 111-120
Author(s):  
A I Skripka ◽  
V V Kogay ◽  
A I Listratov ◽  
A A Sokolova ◽  
D A Napalkov ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Oral Anticoagulant ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Direct Oral Anticoagulant ◽  
Efficacy And Safety ◽  
Future Perspectives ◽  
Theory To Practice ◽  
Personalized Approach

Data on possibilities of personalized approach for direct oral anticoagulants (DOAC) choice in patients with atrial fibrillation are presented in the article. We also review clinical and fundamental studies and future perspectives on pharmacogenetic and pharmacokinetic tests to predict the efficacy and safety of DOAC.

Abstract 20218: Comparative Effectiveness of Dabigatran and Rivaroxaban versus Warfarin in Patients With Non-Valvular Atrial Fibrillation

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Lindsay Bengtson ◽  
Lin Chen ◽  
Richard MacLehose ◽  
Pamela Lutsey ◽  
Alvaro Alonso
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Real World ◽  
Proportional Hazards ◽  
Oral Anticoagulants ◽  
Cox Proportional Hazards ◽  
Intracranial Bleeding ◽  
Gi Bleeding ◽  
Pharmacy Claims ◽  
The Us

Background: In randomized trials, the new oral anticoagulants (NOAC) dabigatran and rivaroxaban have been at least as efficacious as warfarin in the prevention of ischemic stroke in patients with non-valvular atrial fibrillation (NVAF). Information on the effectiveness of NOACs versus warfarin in real-world populations in the US is more limited. Methods: We used data from the US MarketScan Commercial and Medicare Supplemental databases in the period 2010-12. We selected patients initiating oral anticoagulants after NVAF diagnosis, and with at least 6 months of enrollment before first anticoagulant use. Patients initiating dabigatran or rivaroxaban were matched with up to 5 warfarin users by age, sex, and time in the database. Outcomes of interest (ischemic stroke, intracranial bleeding, and gastrointestinal [GI] bleeding) were defined according to validated algorithms. Information on other comorbidities and medication use was obtained from inpatient, outpatient, and pharmacy claims. High-dimensional propensity score-adjusted Cox proportional hazards regression was used to estimate the association of NOACs vs warfarin with each outcome of interest. Results: The analysis included 32,918 dabigatran, 3,301 rivaroxaban and 92,633 warfarin users with NVAF. During an average 13-month follow-up (6 for rivaroxaban, 15 for dabigatran), 1035 ischemic strokes, 225 intracranial bleeds, and 1842 GI bleeds were identified. Rate of ischemic stroke was similar in patients initiating NOACs compared to those on warfarin. However, rate of intracranial bleeding was lower in patients using NOACs compared to warfarin users, while GI bleeding rate was higher in dabigatran users than warfarin users (Table). Conclusion: In this large real-world patient population, effectiveness of NOACs (compared to warfarin) for diverse outcomes was comparable to efficacy reported in the RE-LY and ROCKET-AF trials.

Abstract 15740: Concomitant Use of Dronedarone and Direct Oral Anticoagulants and Risk of Bleeding in Patients With Atrial Fibrillation: An Analysis of the U.S. Truven Health MarketScan Database

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Sampada K Gandhi ◽  
Michael D Ezekowitz ◽  
James A Reiffel ◽  
Rania Boiron ◽  
Mattias Wieloch
Keyword(s):  
Atrial Fibrillation ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Incidence Rates ◽  
Cox Proportional Hazards ◽  
Concomitant Treatment ◽  
Gi Bleeding ◽  
Risk Of Bleeding ◽  
Combined Use ◽  
Increased Risk

Introduction: Dronedarone (DR), a P-gp and CYP 3A4 inhibitor may increase exposure and the risk of bleeding when combined with direct oral anticoagulants (DOACs). Objective: To examine the association between concomitant use of DR and the DOACs, apixaban (A), dabigatran (D), and rivaroxaban (R), and risk of bleeding compared to DOAC monotherapy in patients with atrial fibrillation (AF). Methods: A retrospective cohort study using a U.S. claims database, Truven Health MarketScan identified new users of A, D, and R in patients with AF ≥18 years from Jan 1, 2007 to Sep 30, 2017. Bleeding was defined as hospitalization or emergency room visit with a primary diagnosis of gastrointestinal (GI) bleeding, intracranial hemorrhage (ICH), or bleeding at other sites. Risk of overall and by type of bleeding was examined in concomitant users of DOAC and DR compared to patients using DOAC alone after adjusting for covariates of interest and applying propensity score (PS) trimming via Cox proportional hazards modeling. Results: Among concomitant users of DR and A (1,932), D (3,117), and R (2,395), crude incidence rates of bleeding per 1,000 person-years were 17.2, 37.8, 61.8, respectively versus 26.8, 31.3, and 44.9 in users of A (51,420), D (42,312), and R (57,300) alone. Incidence rates stratified by PS showed higher bleeding incidence in concomitant users of DR with D or R, but not with A. No increased bleeding risk was associated with use of DR and A vs A alone [Adjusted Hazard ratio (aHR): 0.69 (95% CI: 0.40, 1.17), p=0.16]. A modestly increased risk of GI bleeding but not overall bleeding was associated with combined use of DR and D vs D alone [aHR bleeding: 1.18 (95% CI: 0.89, 1.56), p=0.26; aHR GI bleeding: 1.40 (95% CI: 1.01, 1.93); p=0.04]. An increased risk of overall bleeding, driven by GI bleeding, was associated with combined use of DR and R vs R alone [aHR bleeding:1.31 (95% CI: 1.01, 1.69); p=0.04; aHR GI bleeding:1.39 (95% CI: 0.98, 1.95); p=0.06]. There was no increase in the risk of ICH associated with combined use of DR and any DOAC. Conclusions: Concomitant treatment with DR and A showed no increased risk of bleeding, but DR increased the risk of GI bleeding when given with D or R, and of overall bleeding only with R. Concomitant treatment with DR and any DOAC did not increase ICH risk.

Stroke Prevention by Anticoagulants in Daily Practice Depending on Atrial Fibrillation Pattern and Clinical Risk Factors

Stroke ◽  
2021 ◽  
Author(s):  
Lamiae Grimaldi-Bensouda ◽  
Jean-Yves Le Heuzey ◽  
Jean Ferrières ◽  
Didier Leys ◽  
Jean-Marc Davy ◽  
...  
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Vitamin K ◽  
Oral Anticoagulant ◽  
Hemorrhagic Stroke ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Clinical Risk Factors ◽  
Direct Oral Anticoagulant

Background and Purpose: The objective of the study was to assess the effectiveness of individual direct oral anticoagulants versus vitamin K antagonists for primary prevention of stroke (ischemic and hemorrhagic) in routine clinical practice in patients with various clinical risk factors depending on their atrial fibrillation (AF) patterns. Methods: A nested case-referent study was conducted using data from 2 national registries of patients with stroke and AF. Stroke cases with previous history of AF were matched to up to 2 randomly selected referent patients with AF and no stroke. The association of individual anticoagulant use with ischemic or hemorrhagic stroke was studied in patients with or without permanent AF using multivariable conditional logistic models, controlled for clinically significant risk factors and multiple other cardiovascular risk factors. Results: In total, 2586 stroke cases with previous AF and 4810 nonstroke referent patients with AF were retained for the study. Direct oral anticoagulant users had lower odds of stroke of any type than vitamin K antagonist users: the adjusted-matched OR for ischemic stroke were 0.70 (95% CI, 0.50–0.98) for dabigatran, 0.68 (95% CI, 0.53–0.86) for rivaroxaban, and 0.73 (95% CI, 0.52–1.02) for apixaban while for hemorrhagic stroke they were 0.31 (95% CI, 0.14–0.68), 0.64 (95% CI, 0.39–1.06), and 0.70 (95% CI, 0.33–1.49), respectively. The effects of individual direct oral anticoagulants relative to vitamin K antagonists were similar in permanent AF and nonpermanent AF patients. Conclusions: Similar results were observed for each direct oral anticoagulant in real life as those observed in the pivotal clinical trials. The pattern of AF did not affect the outcome.

P4787Use of direct oral anticoagulants in patients with atrial fibrillation having a history of intracranial hemorrhage

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T F Chao ◽  
S A Chen
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Intracranial Hemorrhage ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Research Database ◽  
Bleeding Events ◽  
Risk Of Mortality ◽  
Taiwan National Health Insurance ◽  
History Of

Abstract Background Patients with atrial fibrillation (AF) having a history of intracranial hemorrhage (ICH) were excluded from the pivotal randomized trials comparing direct oral anticoagulants (DOACs) and warfarin. We aimed to compare the effectiveness and safety of DOACs and warfarin among AF patients having a history of ICH. Method A total of 4,540 AF patients having a CHA2DS2-VASc score ≥1 for males and ≥2 for females who had a history of ICH and received oral anticoagulants (DOACs in 3,493 and warfarin in 1,047) were identified from the Taiwan National Health Insurance Research Database. A propensity matching analysis was performed to balance the baseline differences, and 973 patients were finally identified in each groups. Results The risk of ischemic stroke did not differ significantly between warfarin and DOACs (4.41%/yr vs 4.87%/yr; HR 0.985, p=0.927). The risks of bleeding events were lower with DOACs compared to warfarin with a HR (95% CI) of 0.752 (0.573–0.986, p=0.040) for major bleeding and 0.614 (0.379–0.995, p 0.048) for ICH. The risk of mortality was also lower in patients treated with DOACs (HR = 0.539; 95% CI = 0.453–0.642, p<0.001). The cumulative incidence curves of each events for 2 groups are shown in Figure. Conclusion Compared to warfarin, DOACs were associated with a similar risk of ischemic stroke and better safety profiles among AF patient with a history of ICH.

Changes in Oral Anticoagulation Therapy over One Year in 51,000 Atrial Fibrillation Patients at Risk for Stroke: A Practice-Derived Study

2019 ◽  
Vol 119 (06) ◽  
pp. 882-893 ◽  
Author(s):  
Stefan H. Hohnloser ◽  
Edin Basic ◽  
Michael Nabauer
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Proportional Hazards ◽  
Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Cox Proportional Hazards ◽  
Bleeding Events ◽  
Patients At Risk ◽  
Study Population ◽  
Treatment Changes

Background This study assessed changes in anticoagulation therapy over time in patients with atrial fibrillation (AF). Methods Analyses were performed on a claims-based dataset of 4 million health-insured individuals. The study population consisted of patients newly initiating a non-vitamin-K oral anticoagulants (NOACs) or vitamin K antagonist (VKA) for AF between 2013 and 2016. The study outcomes consisted of the proportion of patients who had (1) discontinued OAC treatment, (2) switched from VKA to NOAC, (3) switched from NOAC to VKA or (4) switched from one NOAC to another. Predictors of discontinuation or switching of OAC treatment were determined by Cox proportional hazards regression models with time-independent and time-dependent covariates. Results The study population comprised 51,606 AF patients initiating VKA (n = 21,468, 41.6%), apixaban (n = 8,832, 17.1%), dabigatran (n = 3,973, 7.7%) or rivaroxaban (n = 17,333, 33.6%). After 1 year, 29.9% of VKA and 29.5% of NOAC patients had discontinued OAC treatment without switching to another anticoagulant. A total of 10.7% of VKA patients switched to NOACs within 1 year, whereas 4.9% NOAC patients had switched to VKA. Of AF patients who were initiated on a NOAC, 5.2% switched to another NOAC. Treatment changes among NOAC starters were strongly associated with occurrence of stroke, myocardial infarction and gastrointestinal bleeding after treatment initiation. For VKA starters switching to a NOAC, stroke and bleeding events were associated with an increased likelihood of switching. Conclusion Overall discontinuation rates of VKA and NOACs are comparable over the first year of therapy, while switching from VKA to NOAC was more common than from NOAC to VKA. The majority of treatment changes were associated with clinical events.

The Association between Oral Anticoagulants and Cancer Incidence among Individuals with Nonvalvular Atrial Fibrillation

2020 ◽  
Vol 120 (10) ◽  
pp. 1384-1394
Author(s):  
Devin Abrahami ◽  
Christel Renoux ◽  
Hui Yin ◽  
Jean-Pascal Fournier ◽  
Laurent Azoulay
Keyword(s):  
Atrial Fibrillation ◽  
Pancreatic Cancer ◽  
Proportional Hazards ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Cox Proportional Hazards ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Nonvalvular Atrial Fibrillation

Abstract Objective Existing evidence on the association between vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) and cancer is limited and contradictory. No observational studies have been conducted to simultaneously address the cancer safety of VKAs and DOACs. The objective of this study was to determine whether use of VKAs and DOACs, separately, when compared with nonuse, is associated with cancer overall and prespecified site-specific incidence. Methods Using the United Kingdom Clinical Practice Research Datalink, we identified patients newly diagnosed with nonvalvular atrial fibrillation (NVAF) between 2011 and 2017. Using a time-varying exposure definition, each person-day of follow-up was classified as use of (1) VKAs, (2) DOACs, (3) VKAs and DOACs (drug switchers), and (4) nonuse of anticoagulants (reference). We also conducted a head-to-head comparison of new users of DOACs versus VKAs using propensity score fine stratification weighting. Hazard ratios (HRs) with 95% confidence intervals (CIs) for cancer overall and prespecified subtypes were estimated using Cox proportional hazards models. Results Compared with nonuse, use of VKAs was not associated with cancer overall (HR: 1.05, 95% CI: 0.91–1.22) or cancer subtypes. Similarly, use of DOACs was not associated with cancer overall (HR: 1.13, 95% CI: 0.93–1.37), but an association was observed for colorectal cancer (HR: 1.73, 95% CI: 1.01–2.99), and pancreatic cancer generated an elevated, though nonsignificant HR (HR: 2.15, 95% CI: 0.72–6.44). Results were consistent in the head-to-head comparison. Conclusion Use of oral anticoagulants is not associated with the incidence of cancer overall among patients with NVAF. Possible associations between DOACs and colorectal and pancreatic cancer warrant further study.

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