scholarly journals Direct Oral Anticoagulants in Atrial Fibrillation Patients With Concomitant Hyperthyroidism

2020 ◽  
Vol 105 (9) ◽  
pp. 2893-2904
Author(s):  
Yi-Hsin Chan ◽  
Lung-Sheng Wu ◽  
Lai-Chu See ◽  
Jia-Rou Liu ◽  
Shang-Hung Chang ◽  
...  

Abstract Objective Patients with hyperthyroidism were excluded from the randomized clinical trials of direct oral anticoagulants (DOACs) for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). Methods We performed a nationwide retrospective cohort study using data from the Taiwan National Health Insurance Research Database. We enrolled 3213 and 1181 NVAF patients with hyperthyroidism who were taking DOACs and warfarin, respectively, from June 1, 2012 to December 31, 2017. We also enrolled 53 591 and 16 564 NVAF patients without hyperthyroidism, taking DOACs and warfarin, respectively. We used propensity score stabilized weights (PSSWs) to balance covariates across the study groups. We also used 1:4 matching on both taking DOACs, with (n = 3213) and without hyperthyroidism (n = 12 852); and both taking warfarin, with (n = 1181) and without hyperthyroidism (n = 4724). Results After PSSW, DOAC had a comparable risk of ischemic stroke/systemic embolism (IS/SE) and a lower risk of major bleeding (hazard ratio [HR] 0.65; 95% confidential interval [CI], 0.44–0.96; P = 0.0295) than warfarin among patients with hyperthyroidism. There were comparable risks of IS/SE and major bleeding between those patients with and without hyperthyroidism. However, among patients taking warfarin, those with hyperthyroidism had a lower risk of IS/SE than those without hyperthyroidism (HR 0.61; 95% CI, 0.43–0.86; P = 0.0050). Conclusion Among NVAF Asian patients with concomitant hyperthyroidism, DOACs may be an effective and safer alternative to warfarin. Thromboprophylaxis with DOACs may be considered for such patients, and it is important to validate this finding in further prospective study.

2020 ◽  
Author(s):  
Yi-Hsin Chan ◽  
Hsin-Fu Lee ◽  
Pei-Ru Li ◽  
Jia-Rou Liu ◽  
Tze-Fan Chao ◽  
...  

Abstract Background: Evidence of adverse clinical outcomes for non-vitamin K antagonist oral anticoagulant (NOACs) and warfarin in patients with atrial fibrillation (AF) and diabetes mellitus are limited. We investigated the effectiveness, safety, and major adverse limb events for NOACs versus warfarin among diabetic AF patients.Methods: In this nationwide retrospective cohort study collected from Taiwan National Health Insurance Research Database, we identified a total of 20,967 and 5,812 consecutive AF patients with diabetes taking NOACs and warfarin from June 1, 2012, to December 31, 2017, respectively. We used propensity-score stabilized weighting to balance covariates across study groups.Results: NOAC was associated with a lower risk of major adverse cardiovascular events (MACE) (adjusted hazard ratio (aHR):0.88; [95% confidential interval (CI):0.78-0.99]; P=0.0283), major adverse limb events (MALE) (aHR:0.72;[95%CI:0.57-0.92]; P=0.0083), and major bleeding (aHR:0.67;[95%CI:0.59-0.76];P<.0001) compared to warfarin. NOACs decreased MACE in patients of 75 but not in those aged <75 years (P interaction=0.01), and in patients with ischemic heart disease (IHD) compared to those without IHD (P interaction<0.01). For major adverse limb events, the advantage of risk reduction for NOAC over warfarin persisted in high risk subgroups including age 75 years, chronic kidney disease, IHD, peripheral artery disease, or use of concomitant antiplatelet drugs. Conclusion: Among diabetic AF patients, NOACs were associated with a lower risk of thromboembolism, major bleeding, and major adverse limb events than warfarin. Thromboprophylaxis with NOACs should be considered in the diabetic AF population with a high atherosclerotic burden.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T F Chao ◽  
G Y H Lip ◽  
S A Chen

Abstract Background Patients with atrial fibrillation (AF) and severe liver cirrhosis were excluded from the pivotal randomized trials comparing direct oral anticoagulants (DOACs) and warfarin. In the present study, we compared the effectiveness and safety of DOACs and warfarin among AF patients with liver cirrhosis. Method A total of 3,691 AF patients with liver cirrhosis having a CHA2DS2-VASc score ≥1 for males and ≥2 for females and received oral anticoagulants (DOACs in 2,548 and warfarin in 1,143) were identified from the Taiwan National Health Insurance Research Database. The effectiveness and safety were compared between DOACs and warfarin groups. Results There was a trend suggesting a lower risk of ischemic stroke with DOACs compared to warfarin (2.91%/yr vs 3.41%/yr; HR 0.743, p=0.060). The risks of bleeding events were lower with DOACs compared to warfarin with a HR (95% CI) of 0.718 (0.573–0.899, p=0.004) for major bleeding and 0.509 (0.292–0.889, p=0.018) for ICH. The risk of mortality was also lower in patients treated with DOACs (HR=0.483; 95% CI: 0.424–0.551, p<0.001). The cumulative incidence curves of each events for 2 groups are shown in Figure. The results were essentially similar after the propensity matching analysis of 2 groups. Conclusion Compared to warfarin, DOACs were associated with a lower risk of ICH, major bleeding and mortality among AF patient with liver cirrhosis.


2019 ◽  
Vol 25 ◽  
pp. 107602961987024 ◽  
Author(s):  
Christine L. Baker ◽  
Amol D. Dhamane ◽  
Jigar Rajpura ◽  
Jack Mardekian ◽  
Oluwaseyi Dina ◽  
...  

We compared the risks of switching to another oral anticoagulant (OAC) and discontinuation of direct oral anticoagulants (DOACs) among elderly patients with nonvalvular atrial fibrillation (NVAF) who were prescribed rivaroxaban or dabigatran versus apixaban. Patients (≥65 years of age) with NVAF prescribed DOACs (January 1, 2013 to September 30, 2017) were identified from the Humana research database and grouped into DOAC cohorts. Cox regression analyses were used to evaluate whether the risk for switching to another OAC or discontinuing index DOACs differed among cohorts. Of the study population (N = 38 250), 55.9% were prescribed apixaban (mean age: 78.6 years; 49.8% female), 37.3% rivaroxaban (mean age: 77.4 years; 46.7% female), and 6.8% dabigatran (mean age: 77.0 years; 44.0% female). Compared to patients prescribed apixaban, patients prescribed rivaroxaban (hazard ratio [HR]: 2.08; 95% confidence interval [CI], 1.92-2.25; P < .001) or dabigatran (HR: 3.74; 95% CI, 3.35-4.18, P < .001) had a significantly higher risk of switching to another OAC during the follow-up; compared to patients prescribed apixaban, the risks of discontinuation were also higher for patients treated with rivaroxaban (HR: 1.10; 95% CI, 1.07-1.13, P < .001) or dabigatran (HR: 1.29; 95% CI, 1.23-1.35, P < .001).


2020 ◽  
Author(s):  
Yi-Hsin Chan ◽  
Hsin-Fu Lee ◽  
Pei-Ru Li ◽  
Jia-Rou Liu ◽  
Tze-Fan Chao ◽  
...  

Abstract Background: Evidence of adverse clinical outcomes for non-vitamin K antagonist oral anticoagulant (NOACs) and warfarin in patients with atrial fibrillation (AF) and diabetes mellitus are limited. We investigated the effectiveness, safety, and major adverse limb events for NOACs versus warfarin among diabetic AF patients. Methods: In this nationwide retrospective cohort study collected from Taiwan National Health Insurance Research Database, we identified a total of 20,967 and 5,812 consecutive AF patients with diabetes taking NOACs and warfarin from June 1, 2012, to December 31, 2017, respectively. We used propensity-score stabilized weighting to balance covariates across study groups. Results: NOAC was associated with a lower risk of major adverse cardiovascular events (MACE) (adjusted hazard ratio (aHR):0.88; [95% confidential interval (CI):0.78-0.99]; P =0.0283), major adverse limb events (aHR:0.72;[95%CI:0.57-0.92]; P =0.0083), and major bleeding (aHR:0.67;[95%CI:0.59-0.76]; P <.0001) compared to warfarin. NOACs decreased MACE in patients of 75 but not in those aged <75 years ( P interaction=0.01), and in patients with ischemic heart disease (IHD) compared to those without IHD ( P interaction<0.01). For major adverse limb events, the advantage of risk reduction for NOAC over warfarin persisted in high risk subgroups including age 75 years, chronic kidney disease, IHD, peripheral artery disease, or use of concomitant antiplatelet drugs. Conclusion: NOACs were associated with a lower risk of effectiveness, safety, and major adverse limb events than warfarin among diabetic AF patients. Thromboprophylaxis with NOACs should be considered in the diabetic AF population with a high atherosclerotic burden.


Kardiologiia ◽  
2020 ◽  
Vol 60 (9) ◽  
pp. 102-109
Author(s):  
V. S. Gorbatenko ◽  
A. S. Gerasimenko ◽  
O. V. Shatalova

Aim To compare efficacy and safety of direct oral anticoagulants (DOACs) for prevention of stroke in patients with nonvalvular atrial fibrillation and reduced creatinine clearance.Material and methods Systematic search for literature and indirect comparison of DOACs were performed.Results The indirect comparison included five randomized clinical trials. The DOACs were comparable by the efficacy of preventing stroke and systemic embolism. The safety profiles had differences. Apixaban significantly decreased the relative risk of major bleeding compared to rivaroxaban by 27 % (relative risk (RR) 0.73; 95 % confidence interval (CI): 0.55–0.98). The apixaban advantage was even greater in the group of patients with a creatinine clearance <50 ml/min: RR was reduced by 48 % compared to rivaroxaban (RR=0.52; 95 % CI: 0.32–0.84), by 50 % compared to dabigatran 300 mg/day (RR=0.50; 95 % CI: 0.31–0.81), and by 48 % compared to dabigatran 220 mg/day (RR=0.52; 95 % CI: 0.32–0.85)Conclusion The indirect comparison of DOACs showed that their efficacy was comparable. With respect of safety, apixaban is the preferrable DOAC for patients with atrial fibrillation and creatinine clearance below 50 ml/min.


Stroke ◽  
2020 ◽  
Vol 51 (7) ◽  
pp. 2066-2075 ◽  
Author(s):  
Eric Van Ganse ◽  
Nicolas Danchin ◽  
Isabelle Mahé ◽  
Olivier Hanon ◽  
Flore Jacoud ◽  
...  

Background and Purpose: The effects of direct oral anticoagulants in nonvalvular atrial fibrillation should be assessed in actual conditions of use. France has near-universal healthcare coverage with a unified healthcare information system, allowing large population-based analyses. NAXOS (Evaluation of Apixaban in Stroke and Systemic Embolism Prevention in Patients With Nonvalvular Atrial Fibrillation) aimed to compare the safety, effectiveness, and mortality of apixaban with vitamin K antagonists (VKAs), rivaroxaban, and dabigatran, in oral anticoagulant-naive patients with nonvalvular atrial fibrillation. Methods: This was an observational study using French National Health System claims data and including all adults with nonvalvular atrial fibrillation who initiated oral anticoagulant between 2014 and 2016. Outcomes of interest were major bleeding events leading to hospitalization (safety), stroke and systemic thromboembolic events (effectiveness), and all-cause mortality. Four approaches were used for comparative analyses: matching on propensity score (PS; 1:n); as a sensitivity analysis, matching on high-dimensional PS; adjustment on PS; and adjustment on known confounders. For each outcome, cumulative incidence rates accounting for competing risks of death were estimated. Results: Overall, 321 501 patients were analyzed, of whom 35.0%, 27.2%, 31.1%, and 6.6% initiated VKAs, apixaban, rivaroxaban, and dabigatran, respectively. Apixaban was associated with a lower PS–matched risk of major bleeding compared with VKAs (hazard ratio [HR], 0.43 [95% CI, 0.40–0.46]) and rivaroxaban (HR, 0.67 [95% CI, 0.63–0.72]), but not dabigatran (HR, 0.93 [95% CI, 0.81–1.08]). Apixaban was associated with a lower risk of stroke and systemic thromboembolic event compared with VKAs (HR, 0.60 [95% CI, 0.56–0.65]), but not rivaroxaban (HR, 1.05 [95% CI, 0.97–1.15]) or dabigatran (HR, 0.93 [95% CI, 0.78–1.11]). All-cause mortality was lower with apixaban than with VKAs, but not lower than with rivaroxaban or dabigatran. Conclusions: Apixaban was associated with superior safety, effectiveness, and lower mortality than VKAs; with superior safety than rivaroxaban and similar safety to dabigatran; and with similar effectiveness when compared with rivaroxaban or dabigatran. These observational data suggest potentially important differences in outcomes between direct oral anticoagulants, which should be explored in randomized trials.


Stroke ◽  
2020 ◽  
Vol 51 (3) ◽  
pp. 883-891 ◽  
Author(s):  
Tadataka Mizoguchi ◽  
Kanta Tanaka ◽  
Kazunori Toyoda ◽  
Sohei Yoshimura ◽  
Ryo Itabashi ◽  
...  

Background and Purpose— We aimed to compare outcomes of ischemic stroke patients with nonvalvular atrial fibrillation between earlier and later initiation of direct oral anticoagulants (DOACs) after stroke onset. Methods— From data for 1192 nonvalvular atrial fibrillation patients with acute ischemic stroke or transient ischemic attack in a prospective, multicenter, observational study, patients who started DOACs during acute hospitalization were included and divided into 2 groups according to a median day of DOAC initiation after onset. Outcomes included stroke or systemic embolism, major bleeding, and death at 3 months, as well as those at 2 years. Results— DOACs were initiated during acute hospitalization in 499 patients in median 4 (interquartile range, 2–7) days after onset. Thus, 223 patients (median age, 74 [interquartile range, 68–81] years; 78 women) were assigned to the early group (≤3 days) and 276 patients (median age, 75 [interquartile range, 69–82] years; 101 women) to the late (≥4 days) group. The early group had lower baseline National Institutes of Health Stroke Scale score and smaller infarcts than the late group. The rate at which DOAC administration persisted at 2 years was 85.2% overall, excluding patients who died or were lost to follow-up. Multivariable Cox shared frailty models showed comparable hazards between the groups at 2 years for stroke or systemic embolism (hazard ratio, 0.86 [95% CI, 0.47–1.57]), major bleeding (hazard ratio, 1.39 [95% CI, 0.42–4.60]), and death (hazard ratio, 0.61 [95% CI, 0.28–1.33]). Outcome risks at 3 months also did not significantly differ between the groups. Conclusions— Risks for events including stroke or systemic embolism, major bleeding, and death were comparable whether DOACs were started within 3 days or from 4 days or more after the onset of nonvalvular atrial fibrillation–associated ischemic stroke or transient ischemic attack. Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT01581502.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
L Dominguez Rodriguez ◽  
S Raposeiras Roubin ◽  
D Alonso Rodriguez ◽  
S J Camacho Freire ◽  
E Abuassi ◽  
...  

Abstract Introduction Embolic prevention with oral anticoagulation is the cornerstone for the management of patients with atrial fibrillation (AF). However, data about the efficacy and safety of oral anticoagulation in nonagenarian patients are limited. We aimed to analyze the impact of oral anticoagulation in mortality, embolic and hemorrhagic events, in patients ≥90 years with non-valvular AF. Methods We used data from a multicentric registry of 1,750 consecutive nonagenarian patients diagnosed of AF between 2013 and 2018. A propensity-matched analysis was performed to match the baseline characteristics of patients treated or not with oral anticoagulants, and for those treated with vitamin K antagonists (VKAs) vs direct oral anticoagulants (DOACs). The impact of oral anticoagulation in the embolic and hemorrhagic risk was assessed by a competitive risk analysis, using a Fine and Gray regression model, with death being the competitive event. For embolic risk, we have considered a stroke, pulmonary or peripheral embolism. For bleeding risk, we have considered any bleeding requiring hospital admission. Results The mean of CHA2DS2-VASC and HASBLED scores was 4.5±1.3 and 2.8±1.0 points, respectively. Most of patients were anticoagulated (70.1%; n=1,256). DOACs were used in 709 patients, and VKAs in 517 patients. During a median follow-up of 25.2 months (IQR 12.2–44.3 months), 988 patients died (56.5%), 180 presented embolic events (10.3%), 186 had bleeding events (10.6%), and 29 had intracranial hemorrhage (ICH, 1.7%). After propensity-score matching, anticoagulation (versus non anticoagulation) was associated with lower mortality rate (HR 0.73, 95% CI 0.60–0.89; p=0.002), less mortality and embolic events (HR 0.77, 95% CI 0.64–0.92; p=0.005), but more bleeding events (HR 2.05, 95% CI 1.25–3.35; p=0.004). In comparison with VKAs, DOACs showed similar risk of mortality and embolic events (HR 1.14, 95% CI 0.88–1.47; p=0.337), and similar risk of bleeding events (HR 0.75, 95% CI 0.43–1.28; p=0.287), although a trend to lower risk of ICH was found (HR 0.17, 95% CI 0.02–1.39; p=0.097). Conclusions Among nonagenarian patients with AF, oral anticoagulation was associated with lower all-cause mortality. Although survival free of embolic events was significantly higher in patients with anticoagulation, the risk of major bleeding was twice than in non-anticoagulated patients. There was not differences between VKAs and DOACs in terms of embolic events and total major bleeding. However, compared with VKAs, DOACs were showed a trend to lower risk of ICH.


Stroke ◽  
2021 ◽  
Author(s):  
So-Ryoung Lee ◽  
Eue-Keun Choi ◽  
Sang-Hyun Park ◽  
Jin-Hyung Jung ◽  
Kyung-Do Han ◽  
...  

Background and Purpose: Atrial fibrillation is a risk factor for dementia, and oral anticoagulant use is associated with a decreased risk of dementia in patients with atrial fibrillation. We aimed to investigate whether the risk of dementia would be different between patients treated with direct oral anticoagulants (DOACs) compared with those with warfarin. Methods: Using the Korean nationwide claims database from January 2014 to December 2017, we identified oral anticoagulant–naive nonvalvular atrial fibrillation patients aged ≥40 years. For the comparisons, warfarin and DOAC groups were balanced using the inverse probability of treatment weighting method. The primary outcome was incident dementia. Results: Among 72 846 of total study patients, 25 948 were treated with warfarin, and 46 898 were treated with DOAC (17 193 with rivaroxaban, 9882 with dabigatran, 11 992 with apixaban, and 7831 with edoxaban). During mean 1.3±1.1 years of follow-up, crude incidence of dementia was 4.87 per 100 person-years (1.20 per 100 person-years for vascular dementia and 3.30 per 100 person-years for Alzheimer dementia). Compared with warfarin, DOAC showed a comparable risks of dementia, vascular dementia, and Alzheimer dementia. In subgroup analyses, DOAC was associated with a lower risk of dementia than warfarin, particularly in patients aged 65 to 74 years (hazard ratio, 0.815 [95% CI, 0.709–0.936]) and in patients with prior stroke (hazard ratio, 0.891 [95% CI, 0.820–0.968]). When comparing individual DOACs with warfarin, edoxaban was associated with a lower risk of dementia (hazard ratio, 0.830 [95% CI, 0.740–0.931]). Conclusions: In this large Asian population with atrial fibrillation, DOAC showed a comparable risk of dementia with warfarin overall. DOACs appeared more beneficial than warfarin, in those aged 65 to 74 years or with a history of stroke. For specific DOACs, only edoxaban was associated with a lower risk of dementia than warfarin.


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