scholarly journals 306 The Changing Face of Stroke in the DOAC Era

2019 ◽  
Vol 48 (Supplement_3) ◽  
pp. iii17-iii65
Author(s):  
Recie Davern ◽  
Helena Hobbs ◽  
Hannah Murugan ◽  
Paul Cotter
Keyword(s):  
Atrial Fibrillation ◽  
Oral Anticoagulants ◽  
P Value ◽  
Stroke Management ◽  
Medicines Management ◽  
First Line ◽  
Stroke Registry ◽  
Multiple Factors ◽  
Direct Acting ◽  
Anticoagulated Patients

Abstract Background Patients prescribed oral anticoagulants (OAC) for atrial fibrillation (AF) can still present with stroke. The mechanism for stroke in these patients can be due to multiple factors including subtherapeutic dosing and non-compliance. With the increasing use of direct-acting OACs (DOACs) in favour of warfarin, it is unclear if the incidence of stroke in those already taking OAC has reduced. Methods Data was extracted from our unit’s stroke registry, a prospectively maintained database, for patients who presented with stroke while receiving OAC for AF from 2013 to 2017. Type of OAC, type of stroke, OAC dosing at time of event including non-compliance, stroke management and outcome were recorded. Results 67 patients were included for analysis, with 55 ischaemic and 12 haemorrhagic strokes. 52 patients were receiving warfarin at the time of their stroke vs. 15 receiving DOACs. 33/55 (60%) of ischaemic strokes occurred in patients taking warfarin with a sub-therapeutic INR. In 3/55 (5%) of ischaemic strokes, the OAC was held for a procedure while in 6/55 cases (11%) the OAC had been stopped for another reasons e.g. bleeding. 5/55 (7%) were due to non-compliance. 1 ischaemic stroke was due to under-dosing of a DOAC (dabigatran). 16 strokes were recorded in 2013 for patients prescribed OAC vs. 3 in 2017. Overall the number of ischaemic strokes due to subtherapeutic OAC decreased from 14 in 2013 to 1 in 2017 (p value 0.06). Conclusion The majority of strokes occurring in anticoagulated patients are related to warfarin use. We observed an almost significant reduction in the proportion of ischaemic strokes due to under-dosing of OAC over the study period. Warfarin continues to be recommended as the first line anticoagulant for stroke prevention in atrial fibrillation by the HSE Medicines Management Programme, a decision which we would argue warrants review.

P6248High use of direct oral anticoagulants in elderly patients with non valvular atrial fibrillation: results of REFLEJA study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J Torres Llergo ◽  
M R Fernandez Olmo ◽  
M Carrillo Bailen ◽  
M Puentes Chiachio ◽  
M Martin Toro ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Older Patients ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
P Value ◽  
Hemorrhagic Risk ◽  
Independent Risk Factors ◽  
Artery Disease ◽  
Anticoagulated Patients ◽  
Antiarrhythmic Treatment

Abstract Background Older patients with atrial fibrillation (AF) have a higher thromboembolic and hemorrhagic risk, however oral anticoagulation (OAC) continues to be underutilized. Purpose To analyze the use of direct oral anticoagulant (DOAC) in patients older than 80 years. Methods The REFLEJA study is a single-centre prospective observational registry including 1039 consecutive outpatients with nonvalvular AF. Results Among ≥80 years patients (n=376) there were more women (57.7% vs 41.5%; p<0.001), permanent AF (66.5 vs 42%; <0.001), heart failure (HF) (29.8 vs 20.2%, p<0.001) and vascular disease (19.7 vs 12.8%, p=0.003), although without differences in bleeding (5.9 vs 3,8%, p=0.12) and previous strokes (9.3 vs 7.1%, p=0.20). Despite a higher CHA2DS2-VASc score (4.4±1.1 VS 2.9±1.6, p<0.001), HASBLED score >2 (34.6 vs. 23.7%; p<0.001) and chronic kidney disease (CKD) (51.5 vs. 22.6%, p<0.001), total use of OAC was higher among those older (94.9% vs 90%, p=0.005). There were no differences in the prescription of DOAC (64.1% vs 69.3%, p=0.08), although lower doses (45.8 vs. 12.2%, p<0.005) were more frecuent among older patients. In multivariate analysis, HF (OR 0.60, CI 0.40–0.90; p=0.013) and CKD (OR 0.55, CI 0.41–0.76; p<0.001) were independent risk factors for the prescription of DOAC, but not age ≥80 years (OR 1.16, CI 0.58–2.31, P=0.67). Baseline characteristics Total <80 years ≥80 years p value Hypertension (%) 81.5 77.9 88 <0.001 Diabetes mellitus (%) 26.3 25.7 26.7 0.71 Malignancy (%) 6.6 6.5 6.9 0.78 Coronary artery disease (%) 12.1 10.8 14.4 0.08 Anemia (%) 16.3 12.5 23.2 <0.001 DOAC (%) 67.6 69.3 64.1 0.08 Low doses DOAC (%) 15.9 12.2 45.8 <0.001 CHA2DS2-VASc score 3.4±1.6 2.9±1.6 4.4±1.1 <0.001 HAS-BLED score 1.2±0.8 1.1±0.8 1.4±0.7 <0.001 Glomerular filtration rate (ml/min) 70.9±24.9 76.2±23.1 61.5±25 <0.001 Antiarrhythmic treatment (%) 7.3 9.6 3.1 0.005 Permanent AF 50.5 41.7 66.2 <0.001 DOAC: direct oral anticoagulants; HAS-BLED score: without INR lability; AF: atrial fibrillation. Conclusion The proportion of elderly anticoagulated patients in our environment is very high and advanced age was not associated with a lower use of DOAC.

scholarly journals Meta-analysis comparing the efficacy and safety of direct acting oral anticoagulants to warfarin in patients with atrial fibrillation with and without diabetes

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Shetty ◽  
H Malik
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
P Value ◽  
Efficacy And Safety ◽  
Systemic Embolization ◽  
Direct Acting ◽  
Direct Acting Oral Anticoagulants

Abstract Background Direct-acting oral anticoagulants (DOACs) are now the preferred choice over warfarin in patients with atrial fibrillation (AF). The comparative efficacy and safety of DOACs over warfarin in patients with and without diabetes mellitus (DM) has not been fully evaluated. Purpose To evaluate the efficacy and safety of DOACs compared to warfarin in patients with non-valvular atrial fibrillation with and without DM. Methods A comprehensive review of the literature was performed to identify RCTs with data on DOACs compared to warfarin in the subgroups of DM and nonN-DM. Our outcome of interest were stroke/systemic embolization (SSE) and major bleeding. A random-effects meta-analysis was performed. We further performed a network meta-analysis to assess the most effective of all the therapies for the above mentioned subgroups. Results Our search identified 4 RCTs with 71,683 randomized patients, of which 22,087 were DM and 49,596 were non-DM. The mean duration of follow up was 2.3 years. Our results showed that the DOACS were associated with lower odds for SSE in diabetics (OR 0.80; 95% CI 0.67–0.95; p-value=0.01) and non-diabetics (OR 0.81; 95% CI 0.71–0.92; p-value&lt;0.01). For major bleeding, DOACs were non-inferior to warfarin in DM (OR 0.94; 95% CI 0.80–1.09; p-value=0.42) and non-DM (OR 0.82; 95% CI 0.62–1.07; p-value=0.15). (Fig 1) Network meta-analysis showed that dabigatran was the most effective for the outcome of SSE irrespective of DM status. However, edoxaban and apixaban were the safest of the DOACs for the outcome of major bleeding (Table 1) Conclusion In this meta-analysis of RCT, we found that DOACs are more effective and similarly safe compared to warfarin irrespective of the diabetic status of the patient. 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.

Abstract 16732: Urinary 11-Dehydro-Thromboxane B2 is Associated With Vascular and Non-Vascular Events in Atrial Fibrillation Patients

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Daniele Pastori ◽  
Pasquale Pignatelli ◽  
Roberto Cangemi ◽  
William Hiatt ◽  
Alessio Farcomeni ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Cardiovascular Events ◽  
Oral Anticoagulants ◽  
Cardiovascular Death ◽  
Cox Proportional Hazards ◽  
Thromboxane B2 ◽  
Vascular Events ◽  
Residual Cardiovascular Risk ◽  
Increased Risk ◽  
Anticoagulated Patients

Introduction: Non-Valvular Atrial Fibrillation (AF) patients show high residual cardiovascular risk despite oral anticoagulants. Urinary 11-dehydro-thromboxane B2 (TxB2) is associated with an increased risk of cardiovascular events, but its predictive value in anticoagulated AF patients is unknown. Hypothesis: Aim of this was to assess whether urinary 11-dehydro-TxB2 is a predictor of cardiovascular events in anticoagulated patients with AF. Methods: Prospective single-center cohort study, including 864 consecutive AF patients. Mean time of follow-up was 30.0 months yielding 2062 person-years of observation. Urinary 11-dehydro-TxB2 was measured at baseline. The primary end-point was the composite of myocardial infarction, ischemic stroke, cardiac revascularization, cardiovascular death and deaths from any cause. Results: Cardiovascular events occurred in 98 (11.3%), whilst 81 patients died (9.4%), including 55 from cardiovascular and 26 from non-cardiovascular causes. At baseline, urinary 11-dehydro-TxB2 levels were higher in patients who experienced a cardiovascular event (p<0.001). An increased rate of cardiovascular events, cardiovascular death and all-cause death was observed across tertiles of 11-dehydro-TxB2 (p<0.001). On Cox proportional hazards analysis, CHA2DS2-VASc score, second and third tertile of 11-dehydro-TxB2, compared to the first tertile, were significant predictors of vascular and non-vascular events. On a logistic regression analysis, 11-dehydro-TxB2 levels progressively increase with increasing CHA2DS2-VASc scores. Conclusions: Urinary 11-dehydro-TxB2 predicts residual risk of cardiovascular events in anticoagulated atrial fibrillation patients. Urinary 11-dehydro-TxB2 progressively increases with increasing CHA2DS2-VASc score suggesting that anticoagulated patients with high CHA2DS2-VASc score may need additional antithrombotic strategies.

Abstract TP426: Factors Associated With Oral Anticoagulant Non-Use for Patients With Atrial Fibrillation-Related Stroke: The Florida Puerto Rico Atrial Fibrillation Stroke Study

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Nicole B Sur ◽  
Sebastian Koch ◽  
Kefeng Wang ◽  
Marco R Di Tullio ◽  
Carolina Gutierrez ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Smoking Status ◽  
Oral Anticoagulants ◽  
Private Insurance ◽  
Stroke Severity ◽  
Insurance Status ◽  
Stroke Registry ◽  
Factors Associated ◽  
Stroke Study ◽  
Adjusted Logistic Regression

Background: Oral anticoagulants (OACs) for stroke prevention in atrial fibrillation (AF) are largely underutilized. We identified pre-admission OAC utilization patterns and factors predictive of OAC non-use in patients hospitalized for AF-related stroke. Methods: We included 22,220 patients with ischemic stroke due to previously diagnosed AF enrolled in the Florida Stroke Registry from 2010-2017. A multivariable-adjusted logistic regression model was used to identify factors associated with pre-stroke OAC use for patients with AF-related stroke. Results: A total of 16,246 (73%) patients with AF-related stroke were not on OAC pre-stroke. Compared to patients on OAC, non-OAC patients were more likely to be ≥80 years old, have Medicaid/no insurance, lower CHA 2 DS 2 -VASc scores and greater stroke severity at presentation. After adjustment for age, sex, race-ethnicity, insurance status and vascular risk factors, baseline OAC non-use was higher for patients with Medicaid/no insurance (vs. private insurance, (OR 1.34 [95% CI 1.08-1.67]), smokers (OR 1.29 [1.09-1.52] and patients with NIHSS ≥6 (vs. NIHSS≤5, OR 1.18 [1.11-1.26]). A trend towards greater odds of OAC non-use was seen in women (vs. men, OR 1.07 [0.99-1.14, P=0.07]). Conclusion: The majority of AF-related stroke patients with known AF were not anticoagulated prior to hospitalization for stroke in our study. Insurance status and smoking status had the greatest influence on pre-stroke OAC use. Anticoagulated patients had lower stroke severity on admission. Further efforts are needed to increase OAC use to reduce the burden of stroke for patients with AF, especially for vulnerable populations.

Impact of weight on the efficacy and safety of direct-acting oral anticoagulants in patients with non-valvular atrial fibrillation: a meta-analysis

EP Europace ◽  
2020 ◽  
Vol 22 (3) ◽  
pp. 361-367 ◽  
Author(s):  
Aaqib H Malik ◽  
Srikanth Yandrapalli ◽  
Suchith Shetty ◽  
Wilbert S Aronow ◽  
Diwakar Jain ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Outcome Data ◽  
Phase Iii ◽  
Safety And Efficacy ◽  
Low Bmi ◽  
Direct Acting ◽  
The Impact ◽  
Direct Acting Oral Anticoagulants

Abstract Aims This study sought to determine the impact of weight and body mass index (BMI) on the safety and efficacy of direct-acting oral anticoagulants (DOACs) compared with warfarin in patients with non-valvular atrial fibrillation. Methods and results A systematic literature search was employed in PubMed, Embase, and Cochrane clinical trials with no language or date restrictions. Randomized trials or their substudies were assessed for relevant outcome data for efficacy that included stroke or systemic embolization (SSE), and safety including major bleeding and all-cause mortality. Binary outcome data and odds ratios from the relevant articles were used to calculate the pooled relative risk. For SSE, the data from the four Phase III trials showed that DOACs are better or similarly effective with low BMI 0.73 (0.56–0.97), normal BMI 0.72 (0.58–0.91), overweight 0.87 (0.76–0.99), and obese 0.87 (0.76–1.00). The risk of major bleeding was also better or similar with DOACs in all BMI subgroups with low BMI 0.62 (0.37–1.05), normal BMI 0.72 (0.58–0.90), overweight 0.83 (0.71–0.96), and obese 0.91 (0.81–1.03). There was no impact on mortality in all the subgroups. In a meta-regression analysis, the effect size advantage of DOACs compared with warfarin in terms of safety and efficacy gradually attenuated with increasing weight. Conclusion Our findings suggest that a weight-based dosage adjustment may be necessary to achieve optimal benefits of DOACs for thromboembolic prevention in these patients with non-valvular atrial fibrillation. Further dedicated trials are needed to confirm these findings. PROSPERO 2019 CRD42019140693. Available from: https://www.crd.york.ac.uk/prospero/display_record.php? ID=CRD42019140693.

scholarly journals Efficacy and Safety of Direct Oral Anticoagulants for Atrial Fibrillation Across Body Mass Index Categories

2020 ◽  
Vol 9 (24) ◽  
Author(s):  
Rachel M. Kaplan ◽  
Yoshihiro Tanaka ◽  
Rod S. Passman ◽  
Michelle Fine ◽  
Laura J. Rasmussen‐Torvik ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Body Mass Index ◽  
Body Mass ◽  
Intracranial Hemorrhage ◽  
Oral Anticoagulants ◽  
Efficacy And Safety ◽  
Class 1 ◽  
Direct Acting ◽  
Direct Acting Oral Anticoagulants

Background Direct‐acting oral anticoagulants are now the preferred method of anticoagulation in patients with atrial fibrillation. Limited data on efficacy and safety of these fixed‐dose regimens are available in severe obesity where drug pharmacokinetics and pharmacodynamics may be altered. The objectives of this study were to evaluate efficacy and safety in patients with atrial fibrillation taking direct‐acting oral anticoagulants across body mass index (BMI) categories in a contemporary, real‐world population. Methods and Results We performed a retrospective study of patients with atrial fibrillation at an integrated multisite healthcare system. Patients receiving a direct‐acting oral anticoagulant prescription and ≥12 months of follow‐up between 2010 and 2017 were included. The primary efficacy and safety outcomes were ischemic stroke or systemic embolism and intracranial hemorrhage. We performed Cox proportional hazards modeling to compute hazard ratios (HRs) adjusted for CHA 2 DS 2 ‐VASc score to examine differences by excess BMI categories relative to normal BMI. Of 7642 patients, mean±SD age was 69±12 years with a median (interquartile range) follow‐up of 3.8 (2.2–6.0) years. Approximately 22% had class 1 obesity and 19% had class 2 or 3 obesity. Stroke risks were similar in patients with and without obesity (HR, 1.2; 95% CI, 0.5–2.9; and HR, 0.68; 95% CI, 0.23–2.0 for class 1 and class 2 or 3 obesity compared with normal BMI, respectively). Risk of intracranial hemorrhage was also similar in class 1 and class 2 or 3 obesity compared with normal BMI (HR, 0.64; 95% CI, 0.35–1.2; and HR, 0.66; 95% CI, 0.35–1.2, respectively). Conclusions Direct‐acting oral anticoagulants demonstrated similar efficacy and safety across all BMI categories, even at high weight values.

6072Risk of stroke in hypertensive patients with atrial fibrillation treated with oral anticoagulants

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
R E Harskamp ◽  
W A M Lucassen ◽  
R D Lopes ◽  
H C Van Weert
Keyword(s):  
Atrial Fibrillation ◽  
Blood Pressure ◽  
Vitamin K ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Haemorrhagic Stroke ◽  
Uncontrolled Hypertension ◽  
P Value ◽  
Systemic Embolism ◽  
History Of

Abstract Background Hypertension is common in patients with atrial fibrillation (AF) and carries an additional risk for complications, most notably stroke and bleeding. We assessed the history of hypertension, level of blood pressure control, and an interaction with the choice of oral anticoagulants on clinical outcomes. Purpose To gain insights into the risks of hypertension in the setting of AF and explore possible interactions with the safety and efficacy of non-vitamin K oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs). Methods We performed a systematic review and meta-analysis of studies that randomised patients to NOACs or VKAs and reported outcomes stratified by presence of hypertension. Collected outcomes included: ischaemic stroke or systemic embolism (SE), death from any cause, hemorrhagic stroke, major bleeding, and intracranial hemorrhage. Log adjusted hazard ratios (HR) and corresponding standard error were calculated, and HRs were compared using Mantel-Haenszel random effects. Quality of the evidence was assessed with Cochrane risk of bias tool. Results Five high-quality studies were eligible, including 71,602 participants who received NOACs (apixaban, dabigatran, edoxaban, rivaroxaban) or VKAs, with median follow-up of 1.8–2.8 years. 89.2% of participants had a history of hypertension. Compared with patients without hypertension, those with controlled and uncontrolled hypertension had higher risk for stroke/SE (HR: 1.21 [1.04–1.41] and HR: 1.50 [1.12–2.01], respectively) and haemorrhagic stroke (HR: 1.78 [1.06, 3.00] and HR: 1.66 [0.99–4.01], respectively). On a continuous scale, the risk of stroke increased 7% per 10mmHg increase in systolic blood pressure. As shown in the Table, no interactions were found between hypertension status and the efficacy or safety of NOACs versus VKAs. Table 1. Interaction of presence of hypertension on the comparative efficacy and safety of NOAC versus VKA Hypertension (n=63,869) No hypertension (n=7,733) P-value (int) Adjusted HR, 95% CI Adjusted HR, 95% CI Stroke or systemic embolism 080, 0.72–0.89 0.79, 0.53–1.19 0.98 Haemorrhagic stroke 0.55, 0.41–0.74 0.24, 0.04–1.37 0.36 Death from any cause 0.91, 0.84–0.98 0.89, 0.76–1.04 0.82 Major bleeding 0.90, 0.76–1.07 0.84, 0.69–1.01 0.57 Intracranial haemorrhage 0.41, 0.24-.068 0.48, 0.14–1.69 0.81 Major or clinically relevant non-major bleed 0.90, 0.68–1.18 0.91, 0.55–1.53 0.96 Conclusions Adequate blood pressure management is vital to optimally reduce the risk of stroke in patients with atrial fibrillation. The benefits of NOACs over VKAs, also apply to patients with elevated blood pressure.

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