Anticoagulant therapy in practice

2012 ◽  
Vol 153 (19) ◽  
pp. 732-736
Author(s):  
Gergely Hofgárt ◽  
Csilla Vér ◽  
László Csiba
Keyword(s):  
Atrial Fibrillation ◽  
Risk Factor ◽  
Ischemic Stroke ◽  
Acute Stroke ◽  
Anticoagulant Therapy ◽  
Oral Anticoagulants ◽  
Health Science ◽  
Science Centre ◽  
Improper Use ◽  
Current Guidelines

Atrial fibrillation is a risk factor for ischemic stroke. To prevent stroke oral anticoagulants can be administered. Old and new types of anticoagulants are available. Nowadays, old type, acenocumarol based anticoagulants are used preferentially in Hungary. Aim: The advantages and the disadvantages of anticoagulants are well known, but anticoagulants are underused in many cases. Method: The authors retrospectively examined how frequent atrial fibrillation was and whether the usage of anticoagulants in practice was in accordance with current guidelines among acute stroke cases admitted to the Department of Neurology, Medical and Health Science Centre of Debrecen University in 2009. Results: Of the 461 acute stroke cases, 96 patients had known and 22 patients had newly discovered atrial fibrillation. Half of the patients did not receive proper anticoagulation. Only 8.4% of them had their INR levels within the therapeutic range. Conclusions: The findings are similar to those reported in other studies. Many factors may contribute to the high proportion of improper use of anticoagulants, and further investigations are needed to determine these factors. In any case, elimination of these factors leading to a failure of anticoagulation may decrease the incidence of stroke. Orv. Hetil., 2012, 153, 732–736.

P4776Age-dependent anti-thrombotic therapy for atrial fibrillation patients with intermediate risk (CHA2DS2-VASc Score of 1 or 2) of ischemic stroke

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
K M Lee ◽  
M H Kim ◽  
S Y Choi ◽  
S J Kim ◽  
S W Kim ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Risk Factor ◽  
Ischemic Stroke ◽  
Oral Anticoagulants ◽  
Intermediate Risk ◽  
Risk Criterion ◽  
Korean National Health Insurance ◽  
Effect Of Age ◽  
Annual Risk

Abstract Background Although older age is one of the most important risk factor for stroke in atrial fibrillation (AF), it is unclear whether oral anticoagulants are beneficial for AF patients with intermediate CHA2DS2-VASc score (1 for male or 2 for female) according to age threshold. We sought to investigate the effect of age-dependent antithrombotic therapy for ischemic stroke in Korean intermediate risk AF patients. Methods We enrolled 29,592 patients (males with CHA2DS2-VASc score of 1 and females with CHA2DS2-VASc score of 2) using the Korean National Health Insurance Service database. The clinical endpoint was the occurrence of ischemic stroke. The propensity score matching method was used to balance covariates across treated and untreated patients. Results Treated male AF patients were 6,570 (67.1%) with age <55 years, 7,115 (70.9%) with 55–64 years and 6,470 (68.3%) with 65–74 years in each age risk criterion. Also, treated female AF patients were 3,156 (71.3%) with age <55 years, 2,838 (71.0%) with 55–64 years and 3,440 (72.6%) with 65–74 years in each age risk criterion. Among male and female patients (age <55 years and 55–64 years) with 1 risk factor, an annual ischemic stroke rate was not significantly different between treated and untreated patients at full follow-up. However, treated AF patients who are in age 65–74 year without other risk factor had a much lower annual risk of ischemic stroke [(1.05%/year (male) and 1.04%/year (female)] compared with untreated patients [(1.77%/year (male) (p<0.026) and 1.86%/year (female) (p<0.041). Conclusions Age is an important predictor in determining the risk of ischemic stroke in AF patients with intermediate CHA2DS2-VASc scores (1 for male or 2 for female). We suggest that the benefit of anti-thrombotic therapy for intermediate risk AF patients depends on age threshold.

scholarly journals PHARMACODYNAMICS OF ORAL ANTICOAGULANTS IN PATIENTS WITH ATRIAL FIBRILLATION IN THE ACUTE PERIOD OF ISCHEMIC STROKE

2021 ◽  
Vol 8 (4) ◽  
pp. 222-232
Author(s):  
V. I. Petrov ◽  
A. S. Gerasimenko ◽  
V. S. Gorbatenko ◽  
O. V. Shatalova
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Anticoagulant Therapy ◽  
Oral Anticoagulants ◽  
Cochrane Library ◽  
Optimal Time ◽  
Thromboembolic Complications ◽  
Acute Period ◽  
History Of ◽  
Patient’S History

Background. Every fifth ischemic stroke is caused by a patient’s history of atrial fibrillation. Nowadays, direct and indirect oral anticoagulants are widely used to prevent thromboembolic complications in patients with atrial fibrillation. However, despite the prescription of this group of drugs, every year 1–2% of patients with atrial fibrillation have an ischemic stroke. In this situation, a number of questions take rise: if it is possible to carry out thrombolytic therapy in the patients who have been taking anticoagulants; if it is worth resuming anticoagulant therapy after a stroke; when exactly this should be done; and what drugs should be used to prevent another stroke.The aim of this review was to summarize the available clinical guidelines and research results on the study of the anticoagu- lant therapy characteristics in patients with atrial fibrillation after an ischemic stroke.Materials and methods. For this review, the information presented in the scientific literature from open and available sourc- es, has been used. The information had been placed in the following electronic databases: PubMed, Scopus, Web of Sci- ence Core Collection, Cochrane Library, ClinicalTrials.gov; Elibrary, Cyberleninka, Google Academy. The covering period was 1997–2020. The search queries were: “ischemic stroke + atrial fibrillation + anticoagulants”; “ischemic stroke + atrial fibrillation + direct oral coagulants” and “atrial fibrillation + ischemic stroke + warfarin” in both Russian and English equivalents.Results and conclusion. Currently, the problem of the use of anticoagulants for the prevention of recurrent thromboembolic complications in patients with AF in the acute period of a stroke, is studied insufficiently. The difficulties are caused by the delivery of TLT in the patients who have been taking DOACs, first of all, due to the impossibility of an accurate assessment of the hemostasis state because of the unavailability of routine specific tests; and second, as a result of the lack of registered antidotes for most drugs, and their high costs. Besides, there are no RCTs dedicated to the study of the optimal time for the resumption or initiation of anticoagulant therapy in the acute period of an IS, and the optimal drugs for this group of patients. Most of the existing recommendations on these aspects, are based on the consensus of experts, and this fact indicates the need for further research in the area under review.

scholarly journals Use of Idarucizumab in Ischemic Stroke: A National Experience in a Middle Income Country and a Concise Review.

2021 ◽  
Author(s):  
Julián Alejandro Rivillas ◽  
Arango Akemi ◽  
Bayona Hernán ◽  
Jaramillo Eugenia ◽  
Amaya Pablo
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Acute Stroke ◽  
Combined Therapy ◽  
Oral Anticoagulants ◽  
Middle Income Country ◽  
Income Country ◽  
Middle Income ◽  
Stroke Treatment

Abstract Background Despite receiving anticoagulation for primary or secondary prevention for atrial fibrillation, new embolic events may occur. Current stroke guidelines contraindicate the use of thrombolysis if oral anticoagulants are used within 48 hours of symptom onset. Idarucizumab may be an alternative for patients receiving dabigatran with an acute stroke when alteplase is indicated. We present a series of four cases of patients who received idarucizumab in neurological emergencies in a middle-income country in Latin America. Methods Using the national pharmacologic surveillance data, we retrospectively collected the cases of idarucizumab used in acute stroke, including retinal thrombosis in Colombia between 2018 and 2020. Results Four male patients with atrial fibrillation received thrombolysis for acute stroke, and two of them received mechanical thrombectomy. No major complications during hospitalization were present. One of the patients that received combined therapy presented with hematuria; the other patient that received thrombolysis presented with groin hematoma, but none required transfusion. All had favorable mRS at discharge and 90-day follow-up. Conclusion The use of thrombolysis after reversal with idarucizumab in patients with ischemic stroke is safe. Our patients presented favorable mRS at discharge and 90-day follow-up. The low number of cases is related to the poor availability of idarucizumab. Only 11 hospitals in 5 cities have storage of the medication. Stronger public policies are needed to guarantee optimal stroke treatment in patients with atrial fibrillation receiving anticoagulation, including access to reversal and reperfusion therapies to reduce further disability, especially in a middle-income country such as Colombia.

scholarly journals Ischemic Stroke With Atrial Fibrillation

Stroke ◽  
2021 ◽  
Author(s):  
Amélie Gabet ◽  
Charles Guenancia ◽  
Gauthier Duloquin ◽  
Valérie Olié ◽  
Yannick Béjot
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Acute Stroke ◽  
Oral Anticoagulants ◽  
Temporal Trends ◽  
Population Based ◽  
Newly Diagnosed ◽  
Medical File ◽  
Oral Anticoagulant Treatment ◽  
Stroke Registry

Background and Purpose: Because of the aging population, an increase in the prevalence of atrial fibrillation (AF) is currently observed, thus leading to a rise in AF-related ischemic stroke (IS). We analyzed the current prevalence of AF among patients with IS, their characteristics, and temporal trends from 2006 to 2017 in the population-based Dijon Stroke Registry. Methods: We used data from the Dijon Stroke Registry, an ongoing population-based study that records all cases of acute stroke among residents of the city of Dijon. All patients with IS between 2006 and 2017 were included. Previous AF was defined if it was mentioned in the medical file before stroke and newly diagnosed AF if it was diagnosed during the diagnostic workup of patients with acute stroke. Results: During the period 2014 to 2017, among the 796 patients with IS recorded in the Dijon Stroke Registry, 239 (30.0%) had AF, of whom 79 (9.9% of total patients with IS) had newly diagnosed AF, and 98 (12.3%) had previous AF treated with oral anticoagulants. Patients with IS with AF had more disabilities and a higher initial severity according to the National Institutes of Health Stroke Scale compared with those without AF. The age-adjusted prevalence of AF in patients with IS increased between 2006 and 2017 (+9% per time period), with an important increase in men aged 65 to 74 years (+81%) and women aged ≥85 years (+24%), and a significant decrease in women aged 65 to 74 years (−39%). The use of oral anticoagulant treatment in previous AF patients increased between 2006 and 2009 and 2014 and 2017 (29.3% to 61.3%, P <0.0001). However, 37.5% of patients with previous AF and CHADS 2 score ≥2 were not treated with OAC. Conclusions: The increase in AF prevalence in patients with IS could be related to a better diagnosis of this condition. The underuse of oral anticoagulation treatment was still observed.

scholarly journals Oral anticoagulation in atrial fibrillation patients at intermediate risk of stroke: a nationwide registry-based cohort (Atrial Fibrillation in Norway – AFNOR)

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
M Anjum ◽  
I Ariansen ◽  
V Hjellvik ◽  
L.J Kjerpeseth ◽  
R Selmer ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Risk Factor ◽  
Ischemic Stroke ◽  
Oral Anticoagulants ◽  
Haemorrhagic Stroke ◽  
Study Cohort ◽  
Prescription Database ◽  
Intermediate Risk ◽  
Net Benefit

Abstract Background The effect of oral anticoagulants (OAC) on prevention of stroke must be carefully balanced against the potential risk of bleeding in patients with atrial fibrillation (AF). The net benefit of OAC in AF patients at intermediate risk of stroke remains unclear. Aim We aimed to determine whether the rates of ischemic and haemorrhagic stroke differ between users and non-users of OAC in a nationwide cohort of AF patients at intermediate risk of stroke. Method We investigated the association between initiation of OAC treatment and rates of ischemic and haemorrhagic stroke in a cohort of Norwegian patients with non-valvular AF aged ≥18 years with one non-sex CHA2DS2-VASc risk factor registered from 2011 to 2018, linking data from the Norwegian Population Registry, Patient Registry, Prescription Database and Cause of Death Registry. Individuals using OAC at baseline were excluded. Each individual had at least a three years look-back period for identification of their first non-sex CHA2DS2-VASc risk factor, after which they entered the study cohort and were followed until occurrence of stroke, death, emigration, higher CHA2DS2-VASc score or end of follow-up on December 31, 2018. Individuals were defined as exposed to OAC from the first redeemed prescription of OAC with a reimbursement code for AF and throughout follow-up. Rates of ischemic and haemorrhagic stroke were calculated as the number of stroke cases per 100 person-years, with 95% confidence intervals (CI). Results During 2011–2018, a total of 61,631 individuals with AF and intermediate risk of stroke were included (mean age 63,8±7,6 years (SD); 37% women), of whom 75% initiated OAC treatment. In total, 1709 ischemic strokes (405 cases in OAC users and 1304 in non-users) were registered during 214,738 person-years, and 378 haemorrhagic strokes (251 cases in OAC users and 127 in non-users) during 213,487 person-years. The rate of ischemic stroke was 0.39 (95% CI, 0.35–0.43) and 1.19 (95% CI, 1.12–1.25) per 100 person-years in OAC users and non-users, respectively. The haemorrhagic stroke rate was 0.24 (95% CI, 0.21–0-27) and 0.12 (95% CI, 0.10–0.14) per 100 person-years in OAC users and non-users, respectively. Both ischemic and haemorrhagic stroke rates were highest among those over 65 years of age (Figure 1). Conclusion In a nationwide cohort of Norwegian AF patients at intermediate risk of stroke, three out of four initiated treatment with OAC. Use of OAC was associated with a considerably lower rate of ischemic stroke compared to non-OAC use. Although haemorrhagic stroke rates were increased in the OAC-users vs. non-users, the hemorrhagic stroke rates were generally low. FUNDunding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Vestre Viken Health Trust Figure 1. Rates of ischemic and haemorrhagic stroke per 100 person-years in AF-patients at intermediate risk of stroke (CHA2DS2-VASc score 1 in men, score 2 in women) by OAC use during 2011 to 2018. Age corresponds to age at attainment of the first non-sex CHA2DS2-VASc risk factor.

scholarly journals Sex-related differences in risk factors, type of treatment received and outcomes in patients with atrial fibrillation and acute stroke: Results from the RAF-study (Early Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation)

2016 ◽  
Vol 2 (1) ◽  
pp. 46-53
Author(s):  
Kateryna Antonenko ◽  
Maurizio Paciaroni ◽  
Giancarlo Agnelli ◽  
Nicola Falocci ◽  
Cecilia Becattini ◽  
...  
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Acute Stroke ◽  
Acute Ischemic Stroke ◽  
Oral Anticoagulants ◽  
International Study ◽  
Early Recurrence ◽  
Cerebral Bleeding ◽  
To Receive

Introduction Atrial fibrillation is an independent risk factor of thromboembolism. Women with atrial fibrillation are at a higher overall risk for stroke compared to men with atrial fibrillation. The aim of this study was to evaluate for sex differences in patients with acute stroke and atrial fibrillation, regarding risk factors, treatments received and outcomes. Methods Data were analyzed from the “Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation” (RAF-study), a prospective, multicenter, international study including only patients with acute stroke and atrial fibrillation. Patients were followed up for 90 days. Disability was measured by the modified Rankin Scale (0–2 favorable outcome, 3–6 unfavorable outcome). Results Of the 1029 patients enrolled, 561 were women (54.5%) ( p < 0.001) and younger ( p < 0.001) compared to men. In patients with known atrial fibrillation, women were less likely to receive oral anticoagulants before index stroke ( p = 0.026) and were less likely to receive anticoagulants after stroke (71.3% versus 78.4%, p = 0.01). There was no observed sex difference regarding the time of starting anticoagulant therapy between the two groups (6.4 ± 11.7 days for men versus 6.5 ± 12.4 days for women, p = 0.902). Men presented with more severe strokes at onset (mean NIHSS 9.2 ± 6.9 versus 8.1 ± 7.5, p < 0.001). Within 90 days, 46 (8.2%) recurrent ischemic events (stroke/TIA/systemic embolism) and 19 (3.4%) symptomatic cerebral bleedings were found in women compared to 30 (6.4%) and 18 (3.8%) in men ( p = 0.28 and p = 0.74). At 90 days, 57.7% of women were disabled or deceased, compared to 41.1% of the men ( p < 0.001). Multivariate analysis did not confirm this significance. Conclusions Women with atrial fibrillation were less likely to receive oral anticoagulants prior to and after stroke compared to men with atrial fibrillation, and when stroke occurred, regardless of the fact that in our study women were younger and with less severe stroke, outcomes did not differ between the sexes.

Abstract WP51: Neurological Severity and Infarct Size in Patients With Acute Ischemic Stroke During DOAC Treatment for Nonvalvular Atrial Fibrillation

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Yo Shibata ◽  
Asako Nakamura ◽  
Masahiro Yasaka ◽  
Takahiro Kuwashiro ◽  
Seiji Gotoh ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Infarct Size ◽  
Acute Stroke ◽  
Acute Ischemic Stroke ◽  
Anticoagulant Therapy ◽  
Therapeutic Range ◽  
Control Group ◽  
Stroke Severity ◽  
Stroke Patients

Background and purpose: Less severe and smaller infarct are features in acute stroke patients treated with warfarin within a therapeutic range of PT-INR than in those without. But it remains unclear the severity and size of infarct in acute stroke patients treated with direct oral anticoagulants [DOAC]. We investigated the features of acute stroke in patients treated with DOAC, warfarin or without. Methods: We enrolled consecutive 190 non-valvular atrial fibrillation patients (mean age 78; 63% male) who developed acute ischemic stroke and classified them into 4 groups, 109 patients with no anticoagulant therapy [Control group], 25 patients with DOAC therapy [DOAC group], 19 patients treated with warfarin within a therapeutic range of PT-INR [>= 1.6 in patients aged 70 years old or older, >= 2.0 in those aged younger than 70 years old, Warfarin well controlled group], and 37 patients treated with warfarin with subtherapeutic PT-INR values [Warfarin not controlled group]. Infarcts sizes were defined as the maximum diameter of infarct, using the brain MRI diffusion-weighted image. Stroke severity on admission were assessed by the National Institutes of Health Stroke Scale[NIHSS].We compared them among the groups. Results: There were no significant differences in preadmission CHADS2 score among the 4 groups. The median infarct size were 31mm (interquartile (IQR) 13-59) in the control group, 10mm (IQR 7.4-38) in the DOAC group, 12mm (IQR 8.0-45) in the warfarin well controlled group, and 24mm (IQR 13-67) in the warfarin not controlled group. The size of infarct was significantly smaller in the DOAC group than the control group (P=0.01). The NIHSS on admission was 4 ([IQR] 2-15) in the control group, 2 (1-6) in the DOAC group, 4 (1-17) in the warfarin well controlled group and 5 (3-17) in e warfarin not controlled group. Stroke severity on admission was also more favorable in the DOAC group when compared with the control group (P=0.03) Conclusions: Smaller and less severe infarct may be feature of acute ischemic stroke during DOAC therapy when compared to that without any anticoagulant therapy.

Safety of early anticoagulation in patients treated with urgent reperfusion for acute ischemic stroke related to non-valvular atrial fibrillation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Giustozzi
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Major Bleeding ◽  
Oral Anticoagulation ◽  
Primary Outcome ◽  
Oral Anticoagulants ◽  
Early Recurrence ◽  
Optimal Timing ◽  
Hemorrhagic Event

Abstract Background The optimal timing for starting anticoagulation after an acute ischemic stroke related to non-valvular atrial fibrillation (AF) remains a challenge, especially in patients treated with systemic thrombolysis or mechanical thrombectomy. Purpose We aimed to assess the rates of early recurrence and major bleeding in patients with acute ischemic stroke and AF treated with thrombolytic therapy and/or thrombectomy who received oral anticoagulants for secondary prevention. Methods We combined the dataset of the RAF and the RAF-NOACs studies, which were prospective observational studies carried out from January 2012 to March 2014 and April 2014 to June 2016, respectively. We included consecutive patients with acute ischemic stroke and AF treated with either vitamin K antagonists (VKAs) or new oral anticoagulants (NOACs). Primary outcome was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding within 90 days from the inclusion. Results A total of 2,159 patients were included in the RAF and RAF-NOACs trials, of which 564 patients (26%) were treated with urgent reperfusion therapy. After acute stroke, 505 (90%) patients treated with reperfusion and 1,287 out of the 1,595 (81%) patients not treated with reperfusion started oral anticoagulation. Timing of starting oral anticoagulation was similar in reperfusion-treated and untreated patients (13.5±23.3 vs 12.3±18.3 days, respectively, p=0.287). At 90 days, the composite rate of recurrence and major bleeding occurred in 37 (7%) of patients treated with reperfusion treatment and in 139 (9%) of untreated patients (p=0.127). Twenty-four (4%) reperfusion-treated patients and 82 (5%) untreated patients had early recurrence while major bleeding occurred in 13 (2%) treated and in 64 (4%) untreated patients, respectively. Seven patients in the untreated group experienced both an ischemic and hemorrhagic event. Figure 1 shows the risk of early recurrence and major bleeding over time in patients treated and not treated with reperfusion treatments. The use of NOACs was associated with a favorable rate of the primary outcome compared to VKAs (Odd ratio 0.4, 95% Confidence Interval 0.3–0.7). Conclusions Reperfusion treatment did not influence the risk of early recurrence and major bleeding in patients with AF-related acute ischemic stroke who started anticoagulant treatment. Figure 1 Funding Acknowledgement Type of funding source: None

scholarly journals The Number of Concomitant Drugs and the Safety of Direct Oral Anticoagulants in Routine Care Patients with Atrial Fibrillation

TH Open ◽  
2020 ◽  
Vol 04 (04) ◽  
pp. e417-e426
Author(s):  
Carline J. van den Dries ◽  
Sander van Doorn ◽  
Patrick Souverein ◽  
Romin Pajouheshnia ◽  
Karel G.M. Moons ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Routine Care ◽  
P Value ◽  
Risk Of Mortality ◽  
Mortality Effect

Abstract Background The benefit of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) on major bleeding was less prominent among atrial fibrillation (AF) patients with polypharmacy in post-hoc randomized controlled trials analyses. Whether this phenomenon also exists in routine care is unknown. The aim of the study is to investigate whether the number of concomitant drugs prescribed modifies safety and effectiveness of DOACs compared with VKAs in AF patients treated in general practice. Study Design Adult, nonvalvular AF patients with a first DOAC or VKA prescription between January 2010 and July 2018 were included, using data from the United Kingdom Clinical Practice Research Datalink. Primary outcome was major bleeding, secondary outcomes included types of major bleeding, nonmajor bleeding, ischemic stroke, and all-cause mortality. Effect modification was assessed using Cox proportional hazard regression, stratified for the number of concomitant drugs into three strata (0–5, 6–8, ≥9 drugs), and by including the continuous variable in an interaction term with the exposure (DOAC vs. VKA). Results A total of 63,600 patients with 146,059 person-years of follow-up were analyzed (39,840 person-years of DOAC follow-up). The median age was 76 years in both groups, the median number of concomitant drugs prescribed was 7. Overall, the hazard of major bleeding was similar between VKA-users and DOAC-users (hazard ratio [HR] 0.98; 95% confidence interval [CI] 0.87–1.11), though for apixaban a reduction in major bleeding was observed (HR 0.81; 95% CI 0.68–0.98). Risk of stroke was comparable, while risk of nonmajor bleeding was lower in DOAC users compared with VKA users (HR 0.92; 95% CI 0.88–0.97). We did not observe any evidence for an impact of polypharmacy on the relative risk of major bleeding between VKA and DOAC across our predefined three strata of concomitant drug use (p-value for interaction = 0.65). For mortality, however, risk of mortality was highest among DOAC users, increasing with polypharmacy and independent of the type of DOAC prescribed (p-value for interaction <0.01). Conclusion In this large observational, population-wide study of AF patients, risk of bleeding, and ischemic stroke were comparable between DOACs and VKAs, irrespective of the number of concomitant drugs prescribed. In AF patients with increasing polypharmacy, our data appeared to suggest an unexplained yet increased risk of mortality in DOAC-treated patients, compared with VKA recipients.

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