Anticoagulant prescribing for atrial fibrillation and risk of incident dementia

ObjectiveThe aim of this study was to investigate the association between oral anticoagulant type (direct oral anticoagulants (DOACs) vs vitamin K antagonists (VKAs)) and incident dementia or mild cognitive impairment (MCI) among patients with newly diagnosed atrial fibrillation (AF).MethodsUsing linked electronic health record (EHR) data from the Clinical Practice Research Datalink in the UK, we conducted a historical cohort study among first-time oral anticoagulant users with incident non-valvular AF diagnosed from 2012 to 2018. We compared the incidence of (1) clinically coded dementia and (2) MCI between patients prescribed VKAs and DOACs using Cox proportional hazards regression models, with age as the underlying timescale, accounting for calendar time and time on treatment, sociodemographic and lifestyle factors, clinical comorbidities and medications.ResultsOf 39 200 first-time oral anticoagulant users (44.6% female, median age 76 years, IQR 68–83), 20 687 (53%) were prescribed a VKA and 18 513 (47%) a DOAC at baseline. Overall, 1258 patients (3.2%) had GP-recorded incident dementia, incidence rate 16.5 per 1000 person-years. DOAC treatment for AF was associated with a 16% reduction in dementia diagnosis compared with VKA treatment in the whole cohort (adjusted HR 0.84, 95% CI: 0.73 to 0.98) and with a 26% reduction in incident MCI (adjusted HR 0.74, 95% CI: 0.65 to 0.84). Findings were similar across various sensitivity analyses.ConclusionsIncident EHR-recorded dementia and MCI were less common among patients prescribed DOACs for new AF compared with those prescribed VKAs.

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Reduced stroke risk without increased bleeding risk in patients with atrial fibrillation and complicated liver cirrhosis treated with oral anticoagulation

European Heart Journal ◽

10.1093/ehjci/ehaa946.0658 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

K Steensig ◽

M Pareek ◽

A.L Krarup ◽

P Sogaard ◽

M Maeng ◽

...

Keyword(s):

Atrial Fibrillation ◽

Liver Cirrhosis ◽

Anticoagulant Therapy ◽

Oral Anticoagulation ◽

Oral Anticoagulant ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Bleeding Risk ◽

Increased Risk ◽

First Time

Abstract Introduction Patients with atrial fibrillation (AF) have an increased risk of thromboembolic events (TE), while patients with complicated liver cirrhosis have an increased risk of both TE and bleeding. Oral anticoagulation reduces the risk of TE in the general group of patients with AF but its use in patients with liver cirrhosis is obscured by their imbalance between endogenous procoagulants and anticoagulants, as well as the lack of data from randomized controlled trials. Purpose To examine the risks of TE and bleeding in patients with AF and complicated liver cirrhosis according to whether oral anticoagulation is initiated. Methods We conducted a nationwide registry-based study of anticoagulant-naive patients with complicated liver cirrhosis and first-time AF diagnosed between 2010–2017. Complicated liver cirrhosis was defined as liver cirrhosis plus one of the following: alcoholism, esophageal varices, ascites or hepatorenal syndrome. Patients were followed for a maximum of 5 years. TE was defined as a composite of ischemic stroke, transient ischemic attack or systemic thromboembolism; and the bleeding endpoint was defined as gastrointestinal, cerebral or urogenital bleeding requiring hospitalization, or any hospital contact with epistaxis. TE risk was estimated by use of the CHA2DS2-VASc score, while bleeding risk was estimated by use of the HAS-BLED score. Outcomes were stratified according to whether an oral anticoagulant (vitamin K antagonists [VKA] or direct oral anticoagulants [DOAC]) was initiated. Results We identified 770 patients with complicated liver cirrhosis and first-time AF. TE events occurred in 7.0% (n=25/359) of patients with a CHA2DS2-VASc score ≤2 versus 20.7% (n=85/411) of patients with a CHA2DS2-VASc score >2. Among 411 patients with a high CHA2DS2-VASc score, 111 (27.0%) were prescribed an oral anticoagulant (OAC+; VKA, n=53 [47.7%], DOAC, n=58 [52.3%]), while 300 (73.0%) were not treated with oral anticoagulation (OAC−). These two groups had comparable baseline data, including HAS-BLED (OAC+ 3.0 [2.5–4.0] versus OAC− 3.0 [2.0–4.0]) and CHA2DS2-VASc (OAC+ 4.0 [3.0–5.0] versus OAC− 4.0 [3.0–5.0]) scores. The 5-year TE risk among patients receiving anticoagulant therapy was 14.4% (n=16/111) versus 23.0% (n=69/300) in patients not treated with anticoagulant therapy (hazard ratio (HR) 0.55 [0.32–0.95]). The difference in bleeding risk was insignificant between the two groups (HR 0.67 [0.35–1.30]). Adjusting for CHA2DS2-VASc, HAS-BLED and prior bleeding requiring hospitalization did not significantly change the HR estimate, and no significant interactions were found. Conclusion TE risk was significantly lower in AF patients with complicated liver cirrhosis treated with oral anticoagulation, without a significantly increased bleeding risk. However, the majority of AF patients with complicated liver cirrhosis are not treated with anticoagulant therapy, indicating a potential for reducing the TE burden in this population. Funding Acknowledgement Type of funding source: None

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

Thrombosis and Haemostasis ◽

10.1055/s-0040-1714213 ◽

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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Abstract 18371: Higher Treatment Persistence of Non-Vitamin K Antagonist Oral Anticoagulants than Vitamin K Antagonists at 1 Year in Non-Valvular Atrial Fibrillation in Real-World Practice

Circulation ◽

10.1161/circ.130.suppl_2.18371 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Carlos Martinez ◽

Christopher Wallenhorst ◽

Anja Katholing ◽

Ben Freedman

Keyword(s):

Atrial Fibrillation ◽

Clinical Practice ◽

Vitamin K ◽

Real World ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Ease Of Use ◽

Practice Research ◽

Clinical Practice Research Datalink ◽

One Year

Introduction: Oral anticoagulants (OAC) are under-utilised in atrial fibrillation (AF). Even patients prescribed an OAC may stop taking the drug soon after treatment initiation, particularly with Vitamin K Antagonists (VKA). The Non-VKA OAC (NOAC) drugs offer greater ease of use, and persistence is likely to be higher. Aim: To determine persistence on treatment in the first year after inception of NOACs and VKA in incident AF in real-world clinical practice. Methods: We studied 24,467 OAC-naïve patients with incident non-valvular AF diagnosed between Jan 2011-Feb 2014, mean age 73.9 ± 12.5, 45.6% female, in a very large UK primary care database (Clinical Practice Research Datalink, CRPD), with full linkage to medication use. Follow up was for a mean of 1.2 ± 0.9 years. The proportion of OAC initiation in the 90 days after first-time AF and of those remaining on OAC one year after initiation were estimated using competing risk survival analyses censoring for use of alternative OAC. Results: NOAC drugs prescribed included Rivaroxaban, Dabigatran and Apixaban. Overall, 12,579 (51.4%) were commenced on an OAC: 11,888 on VKA and 691 on NOAC, within 90 days after incident AF. Amongst all OAC users, the proportion taking NOAC increased from 0.3% in 2011 to 12.3% in 2014. Persistence, defined as the proportion still taking the OAC after one year, declined over the 12 months to 54.3% for VKA and 80.7% for NOAC (Table). Persistence was significantly greater for NOAC than VKA at all time points. Conclusions: There is a progressive fall in VKA use amongst OAC naïve patients with AF in real-world practice to only 54% at 1 year. This contributes to under-utilisation of anticoagulation in AF and would result in an increased rate of stroke. Persistence was significantly improved with NOACs compared to VKA, and this factor alone could lead to reduced stroke burden with increasing uptake of the NOACs.

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HAS-BLED scor system for the assessment of risk of breathing of patients on oral anticoagulant therapy // HAS-BLED skor sistem bodovanja za procjenu rizika od krvarenja pacijenata na oralnoj antikoagulantnoj terapiji

SESTRINSKI ŽURNAL ◽

10.7251/sez0118011d ◽

2018 ◽

Vol 5 (1) ◽

pp. 11

Author(s):

Daniela Dobrovoljski

Keyword(s):

Atrial Fibrillation ◽

Oral Anticoagulant ◽

Oral Anticoagulant Therapy ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Heart Rhythm ◽

Clinical Problem ◽

Coagulation Factors ◽

Heart Rhythm Disorders ◽

Anticoagulant Drugs

Oral anticoagulant drugs (OALs) are effective agents in the prevention and treatment of thromboembolic complications. However, despite standardization and application progression, OALs represent a significant clinical problem because they are small-therapeutic medicines that easily interact with food and medicine, which can substantially affect the increased or weakened therapeutic effect. Oral anticoagulants are 4-hydroxycoumarin derivatives and vitamin K antagonists, and their pharmacological activity is based on inhibition of the synthesis of coagulation factors in the liver. These drugs are effective in the prevention of venous thromboembolism, acute myocardial infarction (AIM), heart rhythm disorders by type of atrial fibrillation, stroke prevention, and the like. The most important and clinically commonly undesirable effect of OAL is bleeding. The risk of bleeding is greatest during the introduction of the drug in therapy and for the first few months of the onset of therapy. HAS-BLED scor is a skoring system developed to estimate the 1-year risk of major bleeding in patients with atrial fibrillation and is also used for other indications.

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Adverse prognosis of incidentally detected ambulatory atrial fibrillation

Thrombosis and Haemostasis ◽

10.1160/th4-04-0383 ◽

2014 ◽

Vol 112 (08) ◽

pp. 276-286 ◽

Cited By ~ 79

Author(s):

Carlos Martinez ◽

Anja Katholing ◽

Saul Freedman

Keyword(s):

Myocardial Infarction ◽

Atrial Fibrillation ◽

Major Bleeding ◽

Antithrombotic Therapy ◽

Oral Anticoagulant ◽

Incidence Rates ◽

Practice Research ◽

Clinical Practice Research Datalink ◽

Antiplatelet Treatment ◽

Stroke Incidence

SummaryIt was the aim of this study to determine prognosis of incidentally detected ambulatory atrial fibrillation (IA-AF) and its response to antithrombotic therapy. We performed a cohort study of 5,555 patients with IA-AF (mean age 70.9 ± 10.1, 38.4% female) and 24,705 age- and gender-matched controls without AF followed three years using UK Clinical Practice Research Datalink. We measured incidence rates of stroke, all-cause mortality, myocardial infarction, major bleeding, and effect of antithrombotic therapy. Patients with IA-AF had mean CHA2DS2VASc score 2.5 ± 1.5, 73% with score ≥2. The stroke incidence rate (IR) was 19.4 (95% confidence interval 17.1 – 21.9)/1,000 person-years vs 8.4 (7.7 – 9.1) in controls (p<0.001), mortality 40.1 (36.8 – 43.6)/1,000 person-years vs 20.9 (19.8 – 22.0) in controls (p<0.001), and myocardial infarction 9.0 (7.5 – 10.8)/1,000 person-years vs 6.5 (5.9 – 7.2) in controls (p<0.001). IRs of all endpoints increased with age. Oral anticoagulant ± antiplatelet therapy received by 51.0% in year following IA-AF was associated with adjusted hazard ratio (HR) of 0.35 (0.17 – 0.71) for stroke, and 0.56 (0.36 – 0.85) for death compared to no therapy, while antiplatelet treatment was associated with a non-significant reduction of HR: 0.81 (0.51 – 1.29) for stroke, and 0.80 (0.55 – 1.15) for death, though both carried a similar small non-significant adjusted excess IR of major bleeding. In conclusion, asymptomatic AF detected incidentally is associated with a significant adverse effect on stroke and death, with reduction in both associated with oral anticoagulant but not antiplatelet treatment. This provides justification to assess cost-effectiveness of community screening to detect unknown AF.

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The Combination of Oral Anticoagulant and Antiplatelet Therapies: Stay One Step Ahead

Journal of Cardiovascular Pharmacology and Therapeutics ◽

10.1177/1074248420923528 ◽

2020 ◽

Vol 25 (5) ◽

pp. 391-398

Author(s):

Fabiana Lucà ◽

Simona Giubilato ◽

Stefania Angela Di Fusco ◽

Angelo Leone ◽

Stefano Poli ◽

...

Keyword(s):

Atrial Fibrillation ◽

Venous Thromboembolism ◽

Antiplatelet Therapy ◽

Oral Anticoagulant ◽

Acute Coronary Syndromes ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Clinical Scenarios ◽

Coronary Syndromes

Antithrombotic drugs, which include antiplatelets and anticoagulants, are effective in prevention and treatment of many cardiovascular disorders such as acute coronary syndromes, stroke, and venous thromboembolism and are among the drugs most commonly prescribed worldwide. The advent of direct oral anticoagulants, which are safer alternatives to vitamin K antagonists and do not require laboratory monitoring, has revolutionized the treatment of nonvalvular atrial fibrillation and venous thromboembolism. The combination of oral anticoagulant and antiplatelet therapy is required in many conditions of great clinical impact such as the coexistence of atrial fibrillation and coronary artery disease, with indication to percutaneous coronary intervention. However, strategies that combine anticoagulant and antiplatelet therapies lead to a significant increase in bleeding rates and it is crucial to find the right combination in the single patient in order to optimize the ischemic and bleeding risk. The aim of this review is to explore the evidence and controversies regarding the optimal combination of anticoagulant and antiplatelet therapy through the consideration of past dogmas and new perspectives from recent clinical trials and to propose a tailored therapeutic approach, according to specific clinical scenarios and individual patient characteristics. In particular, we separately explored the clinical settings of stable and acute coronary syndromes and percutaneous revascularization in patients with atrial fibrillation.

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Which Patients Would Be Willing to Change Anticoagulation From Vitamin-K Antagonists to a New Oral Anticoagulant?

Blood ◽

10.1182/blood.v118.21.4318.4318 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4318-4318

Author(s):

Job Harenberg ◽

Svetlana Marx ◽

Nadja Abou-Ayash ◽

Christophe Kremer ◽

Vera Hoeing ◽

...

Keyword(s):

Atrial Fibrillation ◽

Logistic Regression ◽

Regression Analysis ◽

Vitamin K ◽

Logistic Regression Analysis ◽

Oral Anticoagulant ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

New Oral Anticoagulant ◽

Willingness To Change

Abstract Abstract 4318 New oral anticoagulants have generated promising data on the prophylaxis of systemic and non-systemic embolism in patients with atrial fibrillation and treatment of acute venous thromboembolism and prolonged prophylaxis of recurrent events. For patients on chronic treatment with vitamin-K antagonists (VKA) we analysed the motivation and willingness to change the anticoagulation from VKA to new oral anticoagulants. Patients (n=110) on stable treatment with VKA for at least 3 months (indication for anticoagulation: atrial fibrillation or VTE) completed a validated personality inventory (Freiburger Persönlichkeitsinventar FPI-R), and a self-developed questionnaire on general attitudes regarding anticoagulant therapy (Q1). Patients were divided in two groups according to the reply to the question weather they were willing to switch to a new oral anticoagulant. Out of these sets of questions 7 questions were identified by means of a logistic regression analysis for the willingness to change anticoagulation with VKA to a new oral anticoagulant. The same patients completed this shortened questionnaire (Q2) (n=85) thereafter. Logistic regression analysis defined the 7 items of the FPI and Q1 questionaires as relevant for willingness of patients to change the medication. The probability to change medication was 98% using the 7 questions (Q2) compared to the 2 comlete questionnaires. The items were: extraversion – introversion scale on the FPI-R consisting of 14 questions, and from Q1: hope for a better quality of life with a new anticoagulant, no scepticism for new drugs, wish of a lack of routine monitoring for dose adjustment, relevance of the practitioners opinion, thoughts in the past of alternatives for anticoagulation, and difficulty to adjust the prothrombin time. Using Q2 85% of patients confirmed to be willing to change the anticoagulant drug compared to Q1 (chi square test p<0.0001). Seven questions were identified and confirmed to identify patients for their willingness to change anticoagulation from VKA to a new oral anticoagulant. Disclosures: No relevant conflicts of interest to declare.

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Risk of Recurrent Bleeding Events in Nonvalvular Atrial Fibrillation Treated with Vitamin K Antagonists: A Clinical Practice Research Datalink Study

TH Open ◽

10.1055/s-0039-1698413 ◽

2019 ◽

Vol 03 (04) ◽

pp. e316-e324 ◽

Cited By ~ 1

Author(s):

Raza Alikhan ◽

Cinira Lefevre ◽

Ian Menown ◽

Steven Lister ◽

Alex Bird ◽

...

Keyword(s):

Atrial Fibrillation ◽

Clinical Practice ◽

Vitamin K ◽

Vitamin K Antagonists ◽

Practice Research ◽

Clinical Practice Research Datalink ◽

Recurrent Bleeding ◽

Bleeding Events ◽

Nonvalvular Atrial Fibrillation ◽

The Impact

Abstract Background There is little evidence on how the occurrence of a bleed in individuals on vitamin K antagonists (VKAs) impacts the risk of subsequent bleeds, and thromboembolic and ischemic events. Such information would help to inform treatment decisions following bleeds. Objective To estimate the impact of bleeding events on the risk of subsequent bleeds, venous thromboembolism (VTE), stroke, and myocardial infarction (MI) among patients initiating VKA treatment for new-onset nonvalvular atrial fibrillation (NVAF). Methods We conducted an observational cohort study using a linked Clinical Practice Research Datalink—Hospital Episode Statistics dataset. Among a cohort of individuals with NVAF, the risk of clinically relevant bleeding, VTE, stroke, and MI was compared between the period prior to the first bleed and the periods following each subsequent bleed. The rate and cost of general practitioner (GP) consultations, prescriptions, and hospitalizations were also compared across these periods. Results The risk of clinically relevant bleeding events was observed to be elevated at least twofold in all periods following the first bleeding event. The risk of VTE, stroke, and MI was not found to differ according to the number of clinically relevant bleeding events. The rate and cost of GP consultations, GP prescriptions, and hospitalizations were increased in all periods relative to the period prior to the first bleed. Conclusions The doubling in the risk of bleeding following the first bleed, taken alongside the stable risk of MI, VTE, and stroke, suggests that the risk–benefit balance for VKA treatment should be reconsidered following the first clinically relevant bleed.

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Reduced dose of rivaroxaban and dabigatran vs. vitamin K antagonists in very elderly patients with atrial fibrillation in a nationwide cohort study

EP Europace ◽

10.1093/europace/euz285 ◽

2019 ◽

Cited By ~ 1

Author(s):

Laurent Fauchier ◽

Patrick Blin ◽

Frédéric Sacher ◽

Caroline Dureau-Pournin ◽

Marie-Agnès Bernard ◽

...

Keyword(s):

Atrial Fibrillation ◽

Elderly Patients ◽

Vitamin K ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Real Life ◽

European Medicines Agency ◽

Very Elderly ◽

Clinical Events ◽

First Time

Abstract Aims The real-life benefits and risks of the non-vitamin K antagonist oral anticoagulants for stroke prevention in very elderly patients with atrial fibrillation (AF) are still debated. Methods and results Cohorts of new users of rivaroxaban 15 mg, dabigatran 110 mg, or vitamin K antagonists (VKA) for AF ≥85 years old in 2013 or 2014 were identified in the nationwide French claims database and followed-up for 1 year. Cohorts were compared after 1:1 matching using high-dimensional propensity score. Compared to VKA use and considering 1-year cumulative incidences, risk of stroke, and systemic embolism was not different with rivaroxaban use [hazard ratio 1.14, 95% confidence interval (CI): 0.93–1.40] and lower with dabigatran use (0.77, 95% CI: 0.60–0.99), risk of major bleeding was not different with rivaroxaban use (0.91, 95% CI: 0.74–1.11) and with dabigatran use (0.81, 95% CI: 0.64–1.03), risk of all-cause death was borderline to significance lower with rivaroxaban use (0.91, 95% CI: 0.83–1.00), and lower with dabigatran use (0.87, 95% CI: 0.78–0.97). The risk for a composite of all events above was not different with rivaroxaban use (0.96, 95% CI: 0.88–1.04) and lower with dabigatran use (0.87, 95% CI: 0.79–0.96) as compared with VKA use. The risk for the composite of all events was not different with rivaroxaban use as compared with dabigatran use (1.09, 95% CI: 0.97–1.23). Conclusion This study shows for the first time in more than 25 000 new real-life anticoagulant users for AF aged ≥85 years a neutral overall benefit-risk of rivaroxaban 15 mg vs. VKA and a favourable overall benefit-risk of dabigatran 110 mg vs. VKA on relevant clinical events. Study registration European Medicines Agency EUPAS14567 (www.encepp.eu) and Clinicaltrials.gov id NCT02864758.

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Abstract P021: Oral Anticoagulant Use and Risk of Incident Dementia in Persons With Atrial Fibrillation

Circulation ◽

10.1161/circ.137.suppl_1.p021 ◽

2018 ◽

Vol 137 (suppl_1) ◽

Author(s):

Nemin Chen ◽

Richard F MacLehose ◽

Lin Y Chen ◽

Faye L Norby ◽

Lindsay G Bengtson ◽

...

Keyword(s):

Atrial Fibrillation ◽

Propensity Score ◽

Oral Anticoagulation ◽

Oral Anticoagulant ◽

Lower Risk ◽

Cox Regression ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

International Classification Of Diseases ◽

Incident Dementia

Background: Current guidelines recommend oral anticoagulation for the prevention of stroke in most patients with atrial fibrillation (AF). Direct oral anticoagulants (DOACs) are associated with lower risk of ischemic stroke and intracranial bleeding than warfarin and, therefore, may reduce risk of dementia among patients with AF. Hypothesis: AF patients initiating DOACs for stroke prevention will have lower risk of dementia than patients initiating warfarin. Methods: We used data from two US healthcare claim databases, MarketScan (2007-2015) and Optum Clinformatics (2009-2015). Using validated algorithms, we identified patients with AF who initiated oral anticoagulation. Dementia was defined as having an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code of 290.xx, 294.xx, or 331.0. Comorbidities and use of other medications were defined based on inpatient, outpatient, and pharmacy claims. We performed a series of head-to-head comparisons of different oral anticoagulants (warfarin, dabigatran, rivaroxaban, and apixaban) in propensity score-matched cohorts. In each database, multivariable-adjusted Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident dementia for each comparison of propensity score-matched cohorts, adjusting for age, sex, comorbidities, use of other medications, and markers of socioeconomic status (in the Optum database only). We meta-analyzed database-specific results using a random-effects model. Results: The analysis included 307,099 AF patients from the MarketScan database and 161,346 from the Optum database, of which 6,572 and 4,391 respectively had a diagnosis of incident dementia. Mean follow up ranged between 0.7 to 2.3 years and incident of diagnosed dementia between 7 to 14 cases per 1000 person-years across different oral anticoagulant initiator groups. Patients initiating DOACs had a lower risk of incident dementia than those initiating warfarin (dabigatran: HR 0.85, 95%CI 0.71, 1.01; rivaroxaban: HR 0.85, 95%CI 0.76, 0.94; apixaban: HR 0.80, 95%CI 0.65, 0.97). There were no differences in risk of incident dementia comparing DOAC user groups (dabigatran vs. rivaroxaban: HR 1.02, 95%CI 0.79, 1.32; dabigatran vs. apixaban: HR 0.92, 95%CI 0.63, 1.36; apixaban vs. rivaroxaban: HR 1.01, 95%CI 0.86, 1.19). Conclusions: Patients with AF initiating DOACs experienced lower rates of incident dementia than warfarin users. No obvious benefit was observed for any particular DOAC in relation to dementia rates.

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