3053High mortality in atrial fibrillation patients suffering ischemic stroke, intracranial hemorrhage or a gastrointestinal bleed and associations with the preceding antithrombotic treatment

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J J Komen ◽  
T Forslund ◽  
A K Mantel - Teeuwisse ◽  
O H Klungel ◽  
B Wettermark ◽  
...  

Abstract Background Anticoagulation treatment reduces the risk of stroke but increases the risk of bleeding in atrial fibrillation (AF) patients. There is little data on survival after a stroke or a severe bleed. Objective To analyze 90-day mortality in AF patients after an ischemic stroke, an intracranial hemorrhage (ICH) or a gastrointestinal bleed (GIB) and assess associations with the type of antithrombotic treatment preceding the event. Methods From the Stockholm Healthcare database (n=2.3 million inhabitants) we selected all AF patients suffering from an ischemic stroke, an intracranial bleed, or a severe GIB requiring acute hospital care between July 2011 and August 2018 and assessed 90-day mortality rates. We assessed current use of warfarin, non-vitamin K oral anticoagulants (NOAC), or antiplatelet agents at the time of the event. We used a Cox regression to calculate adjusted hazard ratios (aHRs), adjusting for components of the Charlson Comorbidity Index, the CHADsVASc score, the HAS-BLED score, comedication, and year of inclusion, for the association between treatment preceding the event and mortality. In addition, we performed log-rank tests in propensity score matched cohorts. Results Of 105 313 patients with AF, 6 017 were included after an ischemic stroke, 3 006 after an ICH, and 4 291 after a GIB. 90-day mortality rates were 25.1%, 31.6% and 16.2%, respectively. Patients suffering from an ischemic stroke were the oldest at 81.6±9.8 (S.D:) years of age followed by patients suffering from an ICH (80.2±9.8 years) or a GIB (78.7±10.5 years). A large proportion of patients suffering ischemic stroke (72%) had no anticoagulant treatment preceding the event. After ICH, there was a significantly increased risk of mortality in warfarin compared to NOAC treated patients after adjusting for confounders (aHR: 1.36 CI: 1.04–1.78). Patients receiving antiplatelets or no treatment had significantly higher mortality rates than patients on NOAC treatment, both after an ischemic stroke and a GIB, but there was no significant difference between warfarin and NOACs (aHR 0.84 CI: 0.63–1.12 after ischemic stroke, aHR 0.91 CI: 0.66–1.25 after GIB). Propensity score matched analyses yielded similar results. Survival curves after event Conclusion Mortality rates are high in AF patients suffering from an ischemic stroke, an ICH, or a GIB. NOAC treatment was associated with a lower 90-day mortality after ICH than warfarin, but no such difference was found after ischemic stroke or GIB. After ischemic stroke and GIB, mortality rates were higher in antiplatelet treated and untreated patients compared to NOAC treated patients. Acknowledgement/Funding Swedish Heart Lung Foundation

Author(s):  
Joris J Komen ◽  
Tomas Forslund ◽  
Aukje K Mantel-Teeuwisse ◽  
Olaf H Klungel ◽  
Mia von Euler ◽  
...  

Abstract Aims To analyze 90-day mortality in AF patients after a stroke or a severe bleed and assess associations with the type of antithrombotic treatment at the event. Methods and Results From the Stockholm Healthcare database, we selected 6 017 patients with a known history of AF who were diagnosed with ischemic stroke, 3 006 with intracranial hemorrhage, and 4 291 with a severe gastrointestinal bleed (GIB). The 90-day mortality rates were 25.1% after ischemic stroke, 31.6% after intracranial hemorrhage, and 16.2% after severe GIB. We used Cox regression and propensity score matched analyses to test the association between antithrombotic treatment at the event and 90-day mortality. After intracranial hemorrhage, there was a significantly higher mortality rate in warfarin compared to NOAC treated patients (adjusted hazard ratio (aHR): 1.36 CI: 1.04 – 1.78). After an ischemic stroke and a severe GIB, patients receiving antiplatelets or no antithrombotic treatment had significantly higher mortality rates compared to patients on NOACs, but there was no difference comparing warfarin to NOACs (aHR 0.84 CI: 0.63 – 1.12 after ischemic stroke, aHR 0.91 CI: 0.66 – 1.25 after severe GIB). Propensity score matched analysis yielded similar results. Conclusion Mortality rates were high in AF patients suffering from an ischemic stroke, an intracranial hemorrhage, or a severe GIB. NOAC treatment was associated with a lower 90 day mortality after intracranial hemorrhage than warfarin.


2021 ◽  
Author(s):  
Dicken Kong ◽  
Jiandong Zhou ◽  
Sharen Lee ◽  
Keith Sai Kit Leung ◽  
Tong Liu ◽  
...  

AbstractBackgroundIn this territory-wide, observational, propensity score-matched cohort study, we evaluate the development of transient ischaemic attack and ischaemic stroke (TIA/Ischaemic stroke) in patients with AF treated with edoxaban or warfarin.MethodsThis was an observational, territory-wide cohort study of patients between January 1st, 2016 and December 31st, 2019, in Hong Kong. The inclusion were patients with i) atrial fibrillation, and ii) edoxaban or warfarin prescription. 1:2 propensity score matching was performed between edoxaban and warfarin users. Univariate Cox regression identifies significant risk predictors of the primary, secondary and safety outcomes. Hazard ratios (HRs) with corresponding 95% confidence interval [CI] and p values were reported.ResultsThis cohort included 3464 patients (54.18% males, median baseline age: 72 years old, IQR: 63-80, max: 100 years old), 664 (19.17%) with edoxaban use and 2800 (80.83%) with warfarin use. After a median follow-up of 606 days (IQR: 306-1044, max: 1520 days), 91(incidence rate: 2.62%) developed TIA/ischaemic stroke: 1.51% (10/664) in the edoxaban group and 2.89% (81/2800) in the warfarin group. Edoxaban was associated with a lower risk of TIA or ischemic stroke when compared to warfarin.ConclusionsEdoxaban use was associated with a lower risk of TIA or ischemic stroke after propensity score matching for demographics, comorbidities and medication use.


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Shadi Yaghi ◽  
Eva Mistry ◽  
Adam H De Havenon ◽  
Christopher Leon Guerrero ◽  
Amre Nouh ◽  
...  

Background and Purpose: Multiple studies have established that intravenous thrombolysis with alteplase improves outcome after acute ischemic stroke. However, assessment of thrombolysis’ efficacy in stroke patients with atrial fibrillation (AF) has yielded mixed results. We sought to determine the association of alteplase with mortality, hemorrhagic transformation (HT), infarct volume, and mortality in patients with AF and acute ischemic stroke. Methods: We retrospectively analyzed consecutive acute ischemic stroke patients with AF included in the Initiation of Anticoagulation after Cardioembolic stroke (IAC) study, which pooled data from 8 comprehensive stroke centers in the United States. 1889 (90.6%) had available 90-day follow up data and were included. For our primary analysis we used a cohort of 1367/1889 (72.4%) patients who did not undergo mechanical thrombectomy (MT). Secondary analyses were repeated in the patients that underwent MT (n=522). Binary logistic regression was used to determine whether alteplase use was independently associated with risk of HT, final infarct volume, and 90-day mortality, respectively, adjusting for potential confounders. Results: In our primary analyses we found that alteplase use was independently associated with an increased risk for HT (adjusted OR 2.14, 95% CI 1.49 - 3.07, p <0.001) but overall reduced risk of 90-day mortality (adjusted OR 0.58, 95% CI 0.39 - 0.87, p = 0.009). Among patients undergoing MT, alteplase use was associated with a trend towards a reduction in 90-day mortality (adjusted OR 0.68 95% CI 0.45 - 1.04, p = 0.077). In the subgroup of patients prescribed DOAC treatment (n = 327; 24 received alteplase), alteplase treatment was associated with a trend towards smaller infarct size (< 10 mL), (adjusted OR 0.40, 95% CI 0.15 - 1.12, p = 0.082) without a significant difference in the odds of 90-day mortality (adjusted OR 0.51, 95% CI 0.12 - 2.13, p = 0.357) or hemorrhagic transformation (adjusted OR 0.27, 95% CI 0.03 - 2.07, p = 0.206). Conclusion: Thrombolysis with intravenous alteplase was associated with reduced 90-day mortality in AF patients with acute ischemic stroke not undergoing MT. Further study is required to assess the safety and efficacy of alteplase in AF patients undergoing MT and those on DOACs.


Author(s):  
Chinmay G Deshpande ◽  
Cynthia Willey Temkin ◽  
Robert Laforge ◽  
Stephen Kogut

Introduction: Dabigatran and Rivaroxaban have shown better or similar efficacy to lower stroke risk compared to warfarin in clinical trials. Evidence suggests adherence to cardiac drugs tend to reduce outcomes and cost. Our study is the first to examine the impact of atleast 6 to 12 month adherence to NOACs on ischemic stroke, major bleeding, Deep Vein Thrombosis and Pulmonary Embolism (DVTPE) risk in a propensity score based matched sample. Methods: A retrospective cohort study utilized de-identified data from Optum® Clinformatics™ Data Mart database (OptumInsight, Eden Prairie, MN) (Jan 1, 2010 and Dec 31, 2012). Adult patients with ≥ 1 diagnosis of atrial fibrillation or flutter (ICD9 427.31/32), >1 prescription of NOACs, 6 months pre-index continuous enrollment and CHA2DS2VASC score >1 were included. Adherence was calculated using Proportion of Days Covered (PDC ≥80%) for atleast 6 and 12 months of NOAC use and cohorts (adherent vs. non adherent) were matched on propensity score using Inverse Probability Treatment Weighting (IPTW) controlling for demographic and clinical characteristics at baseline. The risk of ischemic stroke, major bleeding (primary outcomes) and DVTPE (exploratory outcome) was evaluated for the matched cohorts post adherence assessment using Cox regression. Results: Out of 25,150 NOAC patients, a total of 3,629 and 1,946 patients with atleast 6 and 12 months of NOAC use were included. Across 2 cohorts, the mean age of the sample was 65 years, 65% were males and >60% had a moderate-high risk of stroke (CHA2DS2VASC>2). Adherence (PDC ≥80%) was 77% and 76% for patients with 6 and 12 month drug use. Post 12 months of drug use, the overall incidence of bleeding, stroke, and DVTPE in the follow-up period was 4.42%, 1.80%, and 0.82% respectively. Each outcome was analyzed separately to avoid calculation of competing risks. Using Cox models with IPTW balanced cohorts, non-adherence was significantly (p ≤0.05) associated with an increase in stroke (≥ 1.5 fold) and DVTPE (≥ 2 fold) risk in both 6 and 12 month users. The risk of bleeding was not significantly different across adherent vs. non adherent users (Table). Conclusion: In our sample, adherence to NOACs was associated with a reduction in stroke and DVTPE risk but did not substantially increase bleeding risk. Further studies with newer NOACs are warranted.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J J Komen ◽  
P Hjemdahl ◽  
A K Mantel - Teeuwisse ◽  
O H Klungel ◽  
B Wettermark ◽  
...  

Abstract Background Anticoagulation treatment reduces the risk of stroke but increases the risk of bleeding in atrial fibrillation (AF) patients. Antidepressants use is associated with increased risk for stroke and bleeds. Objective To assess the association between antidepressant use in AF patients with oral anticoagulants and bleeding and stroke risk. Methods All AF patients newly prescribed with an oral anticoagulant in the Stockholm Healthcare database (n=2.3 million inhabitants) from July 2011 until 2016 were included and followed for one year or shorter if they stopped claiming oral anticoagulant treatment or had an outcome of interest. Outcomes were severe bleeds and strokes, requiring acute hospital care. During follow-up, patients were considered exposed to antidepressant after claiming a prescription for the duration of the prescription. With a time-varying Cox regression, we assessed the association between antidepressant use and strokes and bleeds, adjusting for confounders (i.e., age, sex, comorbidities, comedication, and year of inclusion). In addition, we performed a propensity score matched analysis to test the robustness of our findings. Results Of the 30,595 patients included after claiming a prescription for a NOAC (n=13,506) or warfarin (n=17,089), 4 303 claimed a prescription for an antidepressant during follow-up. A total of 712 severe bleeds and 551 strokes were recorded in the cohort. Concomitant oral anticoagulant and antidepressant use was associated with increased rates of severe bleeds (4.7 vs 2.7 per 100 person-years) compared to oral anticoagulant treatment without antidepressant use (aHR 1.42, 95% CI: 1.12–1.80), but not significantly associated with increased stroke rates (3.5 vs 2.1 per 100 person-years, aHR 1.23, 95% CI: 0.93–1.62). No significant differences were observed between different oral anticoagulant classes (i.e., warfarin or NOAC) or different antidepressant classes (i.e., SSRI, TCA, or other antidepressant). Additional propensity-score matched analyses yielded similar results but showed a significantly increased risk for stroke (HR: 1.47, 95% CI: 1.08–2.02). Incidence rates of strokes and bleeds Conclusion Concomitant use of an oral anticoagulant and an antidepressant, irrespective of type, is associated with an increased bleeding risk. Increased awareness and a critical consideration for the need of an antidepressant is recommended in this population. Acknowledgement/Funding Swedish Heart Lung Foundation


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J E Strange ◽  
C Sindet-Pedersen ◽  
L Staerk ◽  
E L Grove ◽  
T A Gerds ◽  
...  

Abstract Background Atrial fibrillation (AF) and valvular heart disease (VHD) are both associated with an increased risk of stroke. Outside post-hoc analyses of randomized controlled trials, knowledge on the effectiveness and safety of dabigatran in patients with AF and VHD is scarce. Objectives To compare the risk of all-cause mortality, stroke, and bleeding in patients with AF and VHD treated with dabigatran or a vitamin K antagonist (VKA). Methods All Danish residents are provided a unique personal identification number enabling cross-linking of data from Danish nationwide registries. We identified all patients with AF and VHD initiating treatment with dabigatran or VKA between the 22nd of August 2011 and the 31st of December 2014. We defined VHD as aortic stenosis/regurgitation, mitral regurgitation, bioprosthetic heart valves, mitral-, and aortic valve repair. Outcomes were all-cause mortality, stroke, and bleeding. 2-year standardized absolute risks were calculated from cause-specific Cox regression models with death as competing risk. Results In total, 599 (27.3%) and 1,596 (72.7%) patients initiated treatment with dabigatran and VKA. The 2-year standardized absolute risk of all-cause mortality (95% CI) for VKA was 27.6% (25.1% to 30.1%) and 25.4% (21.8% to 29.0%) for dabigatran with a corresponding absolute risk difference of −2.2% (−6.3% to 1.9%) (Figure 1). The 2-year standardized absolute risk of stroke for VKA was 3.4% (2.3% to 4.5%) and 3.9% (2.2% to 5.5%) for dabigatran with a corresponding absolute risk difference of 0.5% (−1.6% to 2.5%). Lastly, the 2-year standardized absolute risk of bleeding for VKA was 8.2% (6.6% to 9.7%) and 7.6% (5.1% to 10.1%) for dabigatran with a corresponding absolute risk difference of −0.5% (−3.4% to 2.4%). Figure 1 Conclusions In this nationwide cohort study, we found no significant difference in the risk of all-cause mortality, stroke, or bleeding in patients with AF and VHD when comparing VKA to dabigatran.


Author(s):  
Johan Holm ◽  
Buster Mannheimer ◽  
Rickard E Malmström ◽  
Erik Eliasson ◽  
Jonatan D Lindh

Abstract Purpose To study the association between interacting drugs and bleeding or thromboembolism in atrial fibrillation outpatients treated with non-vitamin K antagonist oral anticoagulants (NOACs). Methods Population-based cohort study of outpatients treated with NOACs in Sweden from 2008 to 2017. Patients with atrial fibrillation and newly initiated NOAC treatment were identified in the Prescribed Drug Register. Comorbidities and outcome data were retrieved from the Patient Register and the Cause of Death Register. Cox-regression analyses were performed to evaluate the primary endpoints any severe bleed and ischemic stroke/transient ischemic attack/stroke unspecified during the first six months of treatment. Secondary endpoints were gastrointestinal bleeding, intracranial bleeding, ischemic stroke, and venous thromboembolism. Results Increased risk of any severe bleed was found when NOAC treatment, and drugs with pharmacodynamic effect on bleeding were combined, compared to NOAC only. An increased risk with these combinations was evident for apixaban (hazard ratio (HR) 1.47; 95% CI 1.33–1.63), rivaroxaban (HR 1.7; 95% CI 1.49–1.92), and dabigatran (HR 1.26; 95% CI 1.05–1.52). For apixaban, there was an increased risk of any severe bleed when combined with CYP3A4 and/or P-glycoprotein (P-gp) inhibitors (HR 1.23; 95% CI 1.01–1.5). The use of inducers of CYP3A4 and/or P-gp was low in this cohort, and effects on ischemic stroke/TIA/stroke unspecified could not be established. Conclusion Increased risk of bleeding was seen for pharmacodynamic and pharmacokinetic interactions with NOACs. Prescribers need to be vigilant of the effect of interacting drugs on the risk profile of patients treated with NOACs.


Neurology ◽  
2019 ◽  
Vol 92 (21) ◽  
pp. e2432-e2443 ◽  
Author(s):  
Joan Martí-Fàbregas ◽  
Santiago Medrano-Martorell ◽  
Elisa Merino ◽  
Luis Prats-Sánchez ◽  
Rebeca Marín ◽  
...  

ObjectiveWe tested the hypothesis that the risk of intracranial hemorrhage (ICH) in patients with cardioembolic ischemic stroke who are treated with oral anticoagulants (OAs) can be predicted by evaluating surrogate markers of hemorrhagic-prone cerebral angiopathies using a baseline MRI.MethodsPatients were participants in a multicenter and prospective observational study. They were older than 64 years, had a recent cardioembolic ischemic stroke, and were new users of OAs. They underwent a baseline MRI analysis to evaluate microbleeds, white matter hyperintensities, and cortical superficial siderosis. We collected demographic variables, clinical characteristics, risk scores, and therapeutic data. The primary endpoint was ICH that occurred during follow-up. We performed bivariate and multivariate Cox regression analyses.ResultsWe recruited 937 patients (aged 77.6 ± 6.5 years; 47.9% were men). Microbleeds were detected in 207 patients (22.5%), moderate/severe white matter hyperintensities in 419 (45.1%), and superficial siderosis in 28 patients (3%). After a mean follow-up of 23.1 ± 6.8 months, 18 patients (1.9%) experienced an ICH. In multivariable analysis, microbleeds (hazard ratio 2.7, 95% confidence interval [CI] 1.1–7, p = 0.034) and moderate/severe white matter hyperintensities (hazard ratio 5.7, 95% CI 1.6–20, p = 0.006) were associated with ICH (C index 0.76, 95% CI 0.66–0.85). Rate of ICH was highest in patients with both microbleed and moderate/severe WMH (3.76 per 100 patient-years, 95% CI 1.62–7.4).ConclusionPatients taking OAs who have advanced cerebral small vessel disease, evidenced by microbleeds and moderate to severe white matter hyperintensities, had an increased risk of ICH. Our results should help to determine the risk of prescribing OA for a patient with cardioembolic stroke.ClinicalTrials.gov identifierNCT02238470.


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Reza Bavarsad Shahripour ◽  
Benjamin Shifflett ◽  
Edward Labin ◽  
Morgan Figurelle ◽  
Anna Barminova ◽  
...  

Background: Patients with acute ischemic stroke (AIS) due to atrial fibrillation (afib) may have increased complications from intravenous thrombolysis or endovascular treatment (ET) compared to other stroke subtypes. The purpose of this study was to compare the rates of symptomatic intracranial hemorrhage (sICH) in patients with and without a history of a fib treated with IV rt-PA and/or ET. Methods: Consecutive stroke code activations were retrospectively analyzed from January 2004-June 2020 at an academic comprehensive stroke center. Patients were included if they were treated with IV rt-PA and/or ET within 24 hours of stroke onset. Patients were stratified into the six groups:1-No hx of a fib with ET only, 2-Hx of a fib with ET only, 3-No hx of a fib with IV rt-PA plus ET, 4-Hx of a fib with IV rt-PA plus ET, 5-No hx of a fib with IV rt-PA only, 6-Hx of a fib with IV rt-PA only. Primary outcome was defined as any sICH within 72 hours of treatment using the NINDS definition. Baseline demographics were compared. Chi squared was used to assess differences in sICH rates and logistic regression to compare individual groups. Analyses were both unadjusted and adjusted for baseline NIHSS, age, sex, baseline blood pressure, pre-stroke mRS, smoking status, and baseline glucose. Results: We identified 720 AIS patients who received acute treatment (IV rt-PA: n=578; ET: n=100; IV rt-PA+ET:n=18). There was a significant difference in sex (p=0.005); Hispanic ethnicity (p=0.002); current smoking (p=<0.001); current alcohol use (p=0.03), CHF (p=0.01); and age (p<0.0001) between groups. Baseline NIHSS was significantly higher in Group 4 (23, SD 8, p=<0.001).In adjusted analysis, there was no significant difference in sICH in patients with a fib after receiving IVtPA (OR 1.53, CI 0.47-4.99, p=0.48), ET (OR 0.93 , CI 0-∞, p=1.00), or both (OR 0.25,CI 0.00-9.07, p=0.45) compared to those without afib. There was no significant difference in sICH in adjusted analyses in patients with and without a fib overall (OR 0.93, CI 0-∞, p=1.00). Conclusion: In this study, atrial fibrillation did not have a significant impact on rates of sICH in AIS patients treated with IV rt-PA, ET, or both. This study supports the safety of IV rt-PA, ET, and combination therapy in the atrial fibrillation population.


2020 ◽  
pp. neurintsurg-2020-016720
Author(s):  
Feras Akbik ◽  
Ali Alawieh ◽  
C Michael Cawley ◽  
Brian M Howard ◽  
Frank C Tong ◽  
...  

BackgroundAtrial fibrillation (AF) associated ischemic stroke has worse functional outcomes, less effective recanalization, and increased rates of hemorrhagic complications after intravenous thrombolysis (IVT). Limited data exist about the effect of AF on procedural and clinical outcomes after mechanical thrombectomy (MT).ObjectiveTo determine whether recanalization efficacy, procedural speed, and clinical outcomes differ in AF associated stroke treated with MT.MethodsWe performed a retrospective cohort study of the Stroke Thrombectomy and Aneurysm Registry (STAR) from January 2015 to December 2018 and identified 4169 patients who underwent MT for an anterior circulation stroke, 1517 (36.4 %) of whom had comorbid AF. Prospectively defined baseline characteristics, procedural outcomes, and clinical outcomes were reported and compared.ResultsAF predicted faster procedural times, fewer passes, and higher rates of first pass success on multivariate analysis (p<0.01). AF had no effect on intracranial hemorrhage (aOR 0.69, 95% CI 0.43 to 1.12) or 90-day functional outcomes (aOR 1.17, 95% CI 0.91 to 1.50) after MT, although patients with AF were less likely to receive IVT (46% vs 54%, p<0.0001).ConclusionsIn patients treated with MT, comorbid AF is associated with faster procedural time, fewer passes, and increased rates of first pass success without increased risk of intracranial hemorrhage or worse functional outcomes. These results are in contrast to the increased hemorrhage rates and worse functional outcomes observed in AF associated stroke treated with supportive care and or IVT. These data suggest that MT negates the AF penalty in ischemic stroke.


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