scholarly journals Non–Vitamin K Antagonist Oral Anticoagulants Versus Warfarin in Atrial Fibrillation Patients With Intracerebral Hemorrhage

Stroke ◽  
2019 ◽  
Vol 50 (4) ◽  
pp. 939-946 ◽  
Author(s):  
Peter Brønnum Nielsen ◽  
Flemming Skjøth ◽  
Mette Søgaard ◽  
Jette Nordstrøm Kjældgaard ◽  
Gregory Y.H. Lip ◽  
...  

Background and Purpose— Recurrent bleeding associated with oral anticoagulants (OACs) causes a dilemma in patients with atrial fibrillation (AF) sustaining an intracerebral hemorrhage. Treatment recommendations guiding clinical practice on optimal OAC agent selection in this population are lacking. This study aimed to investigate the comparative effectiveness and safety of non–vitamin K antagonist OAC (NOAC) versus warfarin in patients with AF sustaining an intracerebral hemorrhage. Methods— We conducted a nationwide observational cohort study including patients with AF sustaining an intracerebral hemorrhage and who subsequently claimed an OAC prescription. Contrasts of 1-year risks for ischemic stroke and intracerebral hemorrhage risks were obtained and evaluated by inverse probability treatment weighted absolute risk reduction and risk ratios. Results— Among 622 AF patients with intracerebral hemorrhage, 274 claimed a warfarin prescription and 348 a NOAC prescription. Mean age was 76 years (39% females); 72% had an index nonsevere event and 28% moderate to severe index event according to the Scandinavian Stroke Severity scale. The 1-year ischemic stroke risk was 7.85% for warfarin and 4.01% for NOACs, with a weighted absolute risk reduction of 3.78% (95% CI, −0.15% to 7.71%); the weighted risk ratio was 0.52 (0.27–1.00). For recurrent intracerebral hemorrhage, the risk was 7.00% for warfarin and 5.07% for NOACs. The absolute risk reduction was 1.93% (−2.02% to 5.87%), with an a weighted risk ratio of 0.72 (0.38–1.38). Conclusions— NOACs were associated with a nonsignificant lower risk of ischemic stroke and recurrent intracerebral hemorrhage compared with warfarin. The results add to current recommendations of selecting a NOAC agent for stroke prophylaxis treatment in patients with AF, including those with sustaining an intracerebral hemorrhage.

2019 ◽  
Vol 8 (10) ◽  
pp. 1624 ◽  
Author(s):  
Moon ◽  
Lee ◽  
Choi ◽  
Lee ◽  
Jung ◽  
...  

Background: There are limited data for non-vitamin K antagonist oral anticoagulants (NOACs) impact on outcomes for patients with atrial fibrillation (AF) and valvular heart diseases (VHDs). Methods: We identified patients with AF and associated Evaluated Heartvalves, Rheumatic or Artificial (EHRA) type 2 VHDs, and who had been naïve from the oral anticoagulants in the Korean National Health Insurance Service database between 2014 and 2016 (warfarin: n = 2671; NOAC: n = 3058). For analyzing the effect of NOAC on primary prevention, we excluded those with a previous history of ischemic stroke, intracranial hemorrhage (ICH), and gastrointestinal (GI) bleeding events. To balance covariates, we used the propensity score weighting method. Ischemic stroke, ICH, GI bleeding, major bleeding, all-cause death, and their composite outcome and fatal clinical events were evaluated. Results: During a follow-up with a mean duration of 1.4 years, NOACs were associated with lower risks of ischemic stroke (hazard ratio (HR): 0.71, 95% confidence interval (CI): 0.53–0.96), GI bleeding (HR: 0.50, 95% CI: 0.35–0.72), fatal ICH (HR: 0.28, 95% CI: 0.07–0.83), and major bleeding (HR: 0.61, 95% CI: 0.45–0.80) compared with warfarin. Overall, NOACs were associated with a lower risk of the composite outcome (HR: 0.68, 95% CI: 0.58–0.80). Conclusions: In this nationwide Asian AF population with EHRA type 2 VHDs, NOAC use was associated with lower risks of ischemic stroke, major bleeding, all-cause death, and the composite outcome compared to warfarin use.


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.


2019 ◽  
Vol 6 (5) ◽  
pp. 292-300 ◽  
Author(s):  
Anne-Marie Schjerning Olsen ◽  
Patricia McGettigan ◽  
Thomas Alexander Gerds ◽  
Emil Loldrup Fosbøl ◽  
Jonas Bjerring Olesen ◽  
...  

Abstract Aims Non-vitamin K antagonist oral anticoagulants (NOACs) are displacing vitamin K antagonists (VKAs) for stroke prophylaxis in patients with atrial fibrillation (AF). Concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) could increase gastrointestinal bleeding (GIB) risks among these patients. The aim of this study was to examine the risk of GIB among Danish AF patients taking oral anticoagulants (OACs) and NSAIDs. Methods and results Using nationwide administrative registries, we determined concomitant NSAID use among anticoagulant-naïve patients with AF initiating OACs between August 2011 and June 2017. We calculated short-term absolute risks differences and hazard ratios (HRs) for GIB based on multiple adjusted cause-specific Cox regressions with time-dependent NSAID treatment. Among 41 183 patients [median age 70 years (interquartile range 64–78); 55% men], 21% of patients on NOACs and 18% on VKA were co-prescribed NSAIDs. The differences in absolute risk [95% confidence interval (CI)] of GIB within 14 days of commencing concomitant NSAID therapy (vs. no concomitant NSAID therapy) were 0.10% (0.04–0.18%) for NOACs and 0.13% (0.03–0.24%) for VKA. NOACs overall were associated with less GIB than VKA [HR 0.77 (95% CI 0.69–0.85)]. Compared with OACs alone, concomitant NSAIDs doubled the GIB risk associated with NOACs overall [HR 2.01 (95% CI 1.40–2.61)] and with VKA [HR 1.95 (95% CI 1.21–2.69)]. Conclusion Among this nationwide AF population taking OACs, concomitant NSAID therapy increased the short-term absolute risk of GIB. Non-vitamin K antagonist oral anticoagulants alone were associated with lower GIB risks than VKA but concomitant NSAIDs abolished this advantage. The findings align with post hoc analyses from randomized studies. Physicians should exercise appropriate caution when prescribing NSAIDs for patients with AF taking NOACs or VKA.


2017 ◽  
Vol 12 (6) ◽  
pp. 589-596 ◽  
Author(s):  
George Ntaios ◽  
Vasileios Papavasileiou ◽  
Hans-Chris Diener ◽  
Konstantinos Makaritsis ◽  
Patrik Michel

Background In a previous systematic review and meta-analysis, we assessed the efficacy and safety of nonvitamin-K antagonist oral anticoagulants versus warfarin in patients with atrial fibrillation and stroke or transient ischemic attack. Since then, new information became available. Aim The aim of the present work was to update the results of the previous systematic review and meta-analysis. Methods We searched PubMed until 24 August 2016 for randomized controlled trials using the following search items: “atrial fibrillation” and “anticoagulation” and “warfarin” and “previous stroke or transient ischemic attack.” Eligible studies had to be phase III trials in patients with atrial fibrillation comparing warfarin with nonvitamin-K antagonist oral anticoagulants currently on the market or with the intention to be brought to the market in North America or Europe. The outcomes assessed in the efficacy analysis included stroke or systemic embolism, stroke, ischemic or unknown stroke, disabling or fatal stroke, hemorrhagic stroke, cardiovascular death, death from any cause, and myocardial infarction. The outcomes assessed in the safety analysis included major bleeding, intracranial bleeding, and major gastrointestinal bleeding. We performed fixed effects analyses on intention-to-treat basis. Results Among 183 potentially eligible articles, four were included in the meta-analysis. In 20,500 patients, compared to warfarin, nonvitamin-K antagonist oral anticoagulants were associated with a significant reduction of stroke/systemic embolism (relative risk reduction: 13.7%, absolute risk reduction: 0.78%, number needed to treat to prevent one event: 127), hemorrhagic stroke (relative risk reduction: 50.0%, absolute risk reduction: 0.63%, number needed to treat: 157), any stroke (relative risk reduction: 13.1%, absolute risk reduction: 0.7%, number needed to treat: 142), and intracranial hemorrhage (relative risk reduction: 46.1%, absolute risk reduction: 0.88%, number needed to treat: 113) over 1.8–2.8 years. Conclusions This updated meta-analysis in 20,500 atrial fibrillation patients with previous stroke or transient ischemic attack shows that compared to warfarin non-vitamin-K antagonist oral anticoagulants are associated with a significant reduction of stroke, stroke or systemic embolism, hemorrhagic stroke, and intracranial bleeding.


2020 ◽  
Vol 70 (5) ◽  
pp. 269-283
Author(s):  
Dejana Jovanović

Patients with atrial fibrillation who had a previous transient ischemic attack or ischemic stroke had a significantly high risk of stroke recurrence and the introduction of oral anticoagulants should be mandatory. However, the long-term use of oral anticoagulants increases the risk of developing all types of intracranial hemorrhages. The advantages of non-vitamin K oral anticoagulants (NOACs) compared to warfarin are that they have a significantly lower risk for hemorrhagic stroke. They are preferred in elderly patients, those with small vessel disease, or those with previous intracerebral hemorrhage. The time of NOACs introduction after an ischemic stroke depends on its severity and the rule "1-3-6-12" days should be applied. The reintroduction of NOACs in patients with atrial fibrillation and previous intracerebral hemorrhage depends on its etiology and should be after about 4-8 weeks if the cardioembolic risk is high and the risk for intracranial hemorrhage small.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P.S Yang ◽  
M Shim ◽  
S.H Kang ◽  
S.H Kim ◽  
W.J Kim ◽  
...  

Abstract Background and objectives Non-vitamin K antagonist oral anticoagulants (NOACs) are an effective and safe alternative to warfarin in atrial fibrillation (AF) patients, but there is not enough evidence that NOACs can offer sufficient protection in AF patients concomitantly diagnosed with antiphospholipid syndrome (APS). Use of rivaroxaban has been associated with an increased risk of thrombotic events compared with warfarin in results of the TRAPS trial, but the TRAPS trial is not for AF patients and included only very high-risk APS patients with triple-positive for all 3 antiphospholipid antibodies. We sought to compare thromboembolic events, bleeding, and mortality between NOAC and warfarin in patients with both AF and APS. Methods From the Korean National Health Insurance Service (NHIS) database during the period from January 1, 2011 to December 31, 2016, we identified an warfarin-treated group of patients with AF and APS (n=1,237) who were compared with a 1:1 propensity-matched NOAC treated group (n=1,237). Results After a median follow-up period of 17 months, NOAC-treated patients had lower incidence rates for ischemic stroke (5.9 and 10.5 events per 100 person-years for the NOAC and warfarin groups), major bleeding (4.1 and 8.3 events per 100 person-years, respectively), and all-cause mortality (3.4 and 15.6 events per 100 person-years, respectively) compared with warfarin in patients with AF and APS. Compared with warfarin, NOAC significantly decreased the risk of ischemic stroke (hazard ratio [HR]: 0.60, 95% confidence interval [CI]: 0.47–0.77, p<0.001), major bleeding (HR: 0.54, 95% CI: 0.41–0.72, p<0.001) and all-cause mortality (HR: 0.32, 95% CI: 0.27–0.40, p<0.001) with considering competing risk of death. Conclusions Compared with warfarin, AF patients with APS on NOACs had lower ischemic stroke, major bleeding, and all-cause mortality. Our data suggest that AF patients with APS can be safely and effectively treated with NOACs. Funding Acknowledgement Type of funding source: None


Stroke ◽  
2021 ◽  
Vol 52 (4) ◽  
pp. 1450-1454
Author(s):  
Maurizio Paciaroni ◽  
Giancarlo Agnelli ◽  
Michela Giustozzi ◽  
Valeria Caso ◽  
Elisabetta Toso ◽  
...  

Background and Purpose: Clinical trials on stroke prevention in patients with atrial fibrillation have consistently shown clinical benefit from either warfarin or non–vitamin K antagonist oral anticoagulants (NOACs). NOAC-treated patients have consistently reported to be at lower risk for intracerebral hemorrhage (ICH) than warfarin-treated patients. The aims of this prospective, multicenter, multinational, unmatched, case-control study were (1) to investigate for risk factors that could predict ICH occurring in patients with atrial fibrillation during NOAC treatment and (2) to evaluate the role of CHA 2 DS 2 -VASc and HAS-BLED scores in the same setting. Methods: Cases were consecutive patients with atrial fibrillation who had ICH during NOAC treatment. Controls were consecutive patients with atrial fibrillation who did not have ICH during NOAC treatment. As within the CHA 2 DS 2 -VASc and HAS-BLED scores there are some risk factors in common, several multivariable logistic regression models were performed to identify independent prespecified predictors for ICH events. Results: Four hundred nineteen cases (mean age, 78.8±8.1 years) and 1526 controls (mean age, 76.0±10.3 years) were included in the study. From the different models performed, independent predictors of ICH were increasing age, concomitant use of antiplatelet agents, active malignancy, high risk of fall, hyperlipidemia, low clearance of creatinine, peripheral artery disease, and white matter changes. Low doses of NOACs (given according to label or not) and congestive heart failure were inversely associated with the risk of ICH. HAS-BLED and CHA 2 DS 2 -VASc scores performed poorly in predicting ICH with areas under the curves of 0.496 (95% CI, 0.468–0.525) and 0.530 (95% CI, 0.500–0.560), respectively. Conclusions: Several risk factors were associated to ICH in patients treated with NOACs for stroke prevention but not HAS-BLED and CHA 2 DS 2 -VASc scores.


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