Clinical Outcomes in Atrial Fibrillation Patients With a History of Cancer Treated With Non-Vitamin K Antagonist Oral Anticoagulants: A Nationwide Cohort Study

Background and Purpose: Data on clinical outcomes for nonvitamin K antagonist oral anticoagulant (NOACs) and warfarin in patients with atrial fibrillation and cancer are limited, and patients with active cancer were excluded from randomized trials. We investigated the effectiveness and safety for NOACs versus warfarin among patients with atrial fibrillation with cancer. Methods: In this nationwide retrospective cohort study from Taiwan National Health Insurance Research Database, we identified a total of 6274 and 1681 consecutive patients with atrial fibrillation with cancer taking NOACs and warfarin from June 1, 2012, to December 31, 2017, respectively. Propensity score stabilized weighting was used to balance covariates across study groups. Results: There were 1031, 1758, 411, and 3074 patients treated with apixaban, dabigatran, edoxaban, and rivaroxaban, respectively. After propensity score stabilized weighting, NOAC was associated with a lower risk of major adverse cardiovascular events (hazard ratio, 0.63 [95% CI, 0.50–0.80]; P =0.0001), major adverse limb events (hazard ratio, 0.41 [95% CI, 0.24–0.70]; P =0.0010), venous thrombosis (hazard ratio, 0.37 [95% CI, 0.23–0.61]; P <0.0001), and major bleeding (hazard ratio, 0.73 [95% CI, 0.56–0.94]; P =0.0171) compared with warfarin. The outcomes were consistent with either direct thrombin inhibitor (dabigatran) or factor Xa inhibitor (apixaban, edoxaban, and rivaroxaban) use, among patients with stroke history, and among patients with different type of cancer and local, regional, or metastatic stage of cancer ( P interaction >0.05). When compared with warfarin, NOAC was associated with lower risk of major adverse cardiovascular event, and venous thrombosis in patients aged <75 but not in those aged ≥75 years ( P interaction <0.05). Conclusions: Thromboprophylaxis with NOACs rather than warfarin should be considered for the majority of the atrial fibrillation population with cancer.

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Edoxaban versus warfarin on stroke risk in patients with atrial fibrillation: a territory-wide cohort study

10.1101/2021.01.04.21249209 ◽

2021 ◽

Author(s):

Dicken Kong ◽

Jiandong Zhou ◽

Sharen Lee ◽

Keith Sai Kit Leung ◽

Tong Liu ◽

...

Keyword(s):

Atrial Fibrillation ◽

Cohort Study ◽

Ischemic Stroke ◽

Propensity Score ◽

Ischaemic Stroke ◽

Propensity Score Matching ◽

Lower Risk ◽

Cox Regression ◽

Significant Risk ◽

Risk Predictors

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.

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Effectiveness, Safety, and Major Adverse Limb Events in Atrial Fibrillation Patients with Concomitant Diabetes Mellitus Treated with Non-Vitamin K Antagonist Oral Anticoagulants

10.21203/rs.3.rs-15546/v1 ◽

2020 ◽

Author(s):

Yi-Hsin Chan ◽

Hsin-Fu Lee ◽

Pei-Ru Li ◽

Jia-Rou Liu ◽

Tze-Fan Chao ◽

...

Keyword(s):

Diabetes Mellitus ◽

Atrial Fibrillation ◽

Vitamin K ◽

Lower Risk ◽

Oral Anticoagulants ◽

Study Groups ◽

Vitamin K Antagonist ◽

Major Adverse Cardiovascular Events ◽

Research Database ◽

Atherosclerotic Burden

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.

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Comparison of clinical outcomes with edoxaban versus apixaban, dabigatran, rivaroxaban, and vitamin K antagonist in patients with atrial fibrillation in Germany: a real-world cohort study

European Heart Journal ◽

10.1093/ehjci/ehaa946.0401 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

X.L Marston ◽

R Wang ◽

Y.C Yeh ◽

L Zimmermann ◽

X Ye ◽

...

Keyword(s):

Atrial Fibrillation ◽

Cohort Study ◽

Clinical Outcomes ◽

Vitamin K ◽

Major Bleeding ◽

Real World ◽

Lower Risk ◽

Sensitivity Analyses ◽

Funding Source ◽

Baseline Characteristics

Abstract Background Vitamin K antagonists (VKA) and non-VKA oral anticoagulants (NOACs) are used to prevent thromboembolic conditions in patients with atrial fibrillation (AF). Unlike VKA, NOACs have fixed dosage schemes, do not require regular laboratory tests, and have fewer drug and food interactions. The use of NOACs has increased substantially in recent years in Germany. However, there is limited evidence on the comparative effectiveness and safety between different NOACs and VKA in real-world settings. Purpose The objective of the study was to compare the clinical outcomes, including systemic embolism (SE), ischemic stroke (IS), and major bleeding, of edoxaban with other NOACs (apixaban, dabigatran, rivaroxaban) and VKA in AF patients in Germany. Methods Using an administrative database from our institution (Deutsche Analysedatenbank für Evaluation und Versorgungsforschung) between January 2013 and December 2017, a retrospective cohort study was conducted to compare the effectiveness (risk of SE or IS) and safety (risk of major bleeding) in NOAC-naïve AF patients who initiated anticoagulant therapy. Continuous enrolment for 12 months before anticoagulant initiation was required to assess baseline characteristics. Patients were followed up until (1) the first outcome event (SE, IS, or major bleeding), (2) disenrollment from health plans, or (3) discontinuation of the index NOAC or VKA or therapy switch, whichever occurred first. Inverse probability treatment weighting (IPTW) using propensity score was applied to control for differences in baseline characteristics. Cox proportional hazards models were used to estimate the hazard ratios (HR) for each outcome comparing edoxaban versus other NOACs and VKA. Sensitivity analyses were conducted with follow-up period cut-off at 1 year. Results A total of 1236 edoxaban, 6053 apixaban, 1306 dabigatran, 7013 rivaroxaban, and 5430 VKA patients were included. Patient cohorts were well balanced after weighting. The adjusted risks of SE or IS were lower for edoxaban compared to apixaban (HR 0.83, 95% CI 0.69–0.99), dabigatran (HR 0.54, 95% CI 0.40–0.74), rivaroxaban (HR 0.72, 95% CI 0.60–0.87), and VKA (HR 0.65, 95% CI 0.53–0.78) (all p<0.05). Edoxaban was associated with a significantly lower risk of major bleeding compared to dabigatran (HR 0.73, 95% CI 0.55–0.98), rivaroxaban (HR 0.74, 95% CI 0.63–0.87), and VKA (HR 0.47, 95% CI 0.40–0.55) (all p<0.05). The risk of major bleeding was comparable between edoxaban and apixaban (HR 1.09, 95% CI 0.92–1.30, p=0.33). Results were consistent in the sensitivity analyses. Conclusions Edoxaban was associated with a significantly lower risk of SE or IS compared to other NOACs and VKA, indicating improved effectiveness. Edoxaban also had a favourable safety profile with a significantly lower risk of major bleeding compared to dabigatran, rivaroxaban, and VKA. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): This study was sponsored by Daiichi Sankyo Inc.

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Lower Risk of Dementia in Patients With Atrial Fibrillation Taking Non‐Vitamin K Antagonist Oral Anticoagulants: A Nationwide Population‐Based Cohort Study

Journal of the American Heart Association ◽

10.1161/jaha.120.016437 ◽

2021 ◽

Vol 10 (5) ◽

Author(s):

Jin‐Yi Hsu ◽

Peter Pin‐Sung Liu ◽

An‐Bang Liu ◽

Shu‐Man Lin ◽

Huei‐Kai Huang ◽

...

Keyword(s):

Atrial Fibrillation ◽

Cohort Study ◽

Vitamin K ◽

Lower Risk ◽

Randomized Clinical Trials ◽

Oral Anticoagulants ◽

Population Based ◽

Vitamin K Antagonist ◽

Research Database ◽

Incident Cases

Background A higher risk of developing dementia is observed in patients with atrial fibrillation (AF). Results are inconsistent regarding the risk of dementia when patients with AF use different anticoagulants. We aimed to investigate the risk of dementia in patients with AF receiving non‐vitamin K antagonist oral anticoagulants (NOACs) compared with those receiving warfarin. Methods and Results We conducted a nationwide population‐based cohort study of incident cases using the Taiwan National Health Insurance Research Database. We initially enlisted all incident cases of AF and then selected those treated with either NOACs or warfarin for at least 90 days between 2012 and 2016. First‐ever diagnosis of dementia was the primary outcome. We performed propensity score matching to minimize the difference between each cohort. We used the Fine and Gray competing risk regression model to calculate the hazard ratio (HR) for dementia. We recruited 12 068 patients with AF (6034 patients in each cohort). The mean follow‐up time was 3.27 and 3.08 years in the groups using NOACs and warfarin, respectively. Compared with the HR for the group using warfarin, the HR for dementia was 0.82 (95% CI, 0.73–0.92; P =0.0004) in the group using NOACs. Subgroup analysis demonstrated that users of NOAC aged 65 to 74 years, with a high risk of stroke or bleeding were associated with a lower risk of dementia than users of warfarin with similar characteristics. Conclusions Patients with AF using NOACs were associated with a lower risk of dementia than those using warfarin. Further randomized clinical trials are greatly needed to prove these findings.

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Effectiveness, Safety, and Major Adverse Limb Events in Atrial Fibrillation Patients with Concomitant Diabetes Mellitus Treated with Non-Vitamin K Antagonist Oral Anticoagulants

10.21203/rs.3.rs-15546/v2 ◽

2020 ◽

Author(s):

Yi-Hsin Chan ◽

Hsin-Fu Lee ◽

Pei-Ru Li ◽

Jia-Rou Liu ◽

Tze-Fan Chao ◽

...

Keyword(s):

Diabetes Mellitus ◽

Atrial Fibrillation ◽

Vitamin K ◽

Major Bleeding ◽

Lower Risk ◽

Oral Anticoagulants ◽

Study Groups ◽

Vitamin K Antagonist ◽

Major Adverse Cardiovascular Events ◽

Research Database

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.

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Fracture risks among patients with atrial fibrillation receiving different oral anticoagulants: a real-world nationwide cohort study

European Heart Journal ◽

10.1093/eurheartj/ehz952 ◽

2020 ◽

Vol 41 (10) ◽

pp. 1100-1108 ◽

Cited By ~ 13

Author(s):

Huei-Kai Huang ◽

Peter Pin-Sung Liu ◽

Jin-Yi Hsu ◽

Shu-Man Lin ◽

Carol Chiung-Hui Peng ◽

...

Keyword(s):

Atrial Fibrillation ◽

Cohort Study ◽

Propensity Score ◽

Fracture Risk ◽

Propensity Score Matching ◽

Real World ◽

Cox Regression ◽

Oral Anticoagulants ◽

Research Database ◽

Cox Regression Analysis

Abstract Aims To evaluate the fracture risk among patients with atrial fibrillation (AF) treated with non-vitamin K antagonist oral anticoagulants (NOACs) or warfarin. Methods and results We conducted a real-world nationwide retrospective cohort study using Taiwan’s National Health Insurance Research Database. All adult patients in Taiwan newly diagnosed with AF between 2012 and 2016 who received NOACs or warfarin were enrolled and followed up until 2017. Patients treated with NOACs were sub-grouped according to the NOAC used (dabigatran, rivaroxaban, and apixaban). Propensity score matching was performed for each head-to-head comparison. Cox regression analysis, with a shared frailty model, was used to calculate the adjusted hazard ratios (aHRs) for hip, vertebral, and humerus/forearm/wrist fractures. After matching, 19 414 patients were included (9707 in each NOAC and warfarin groups). The median follow-up time was 2.4 years. Compared with warfarin, NOACs were associated with a reduced fracture risk [aHR = 0.84, 95% confidence interval (CI) = 0.77–0.93; P < 0.001]. Sub-analyses revealed that each NOAC, namely dabigatran (aHR = 0.88, 95% CI = 0.78–0.99; P = 0.027), rivaroxaban (aHR = 0.81, 95% CI = 0.72–0.90; P < 0.001), and apixaban (aHR = 0.67, 95% CI = 0.52–0.87; P = 0.003), had a reduced fracture risk. Analyses including all eligible patients, without propensity score matching, generated similar results. Conclusion Compared with warfarin, NOAC was associated with a reduced fracture risk among AF patients. Therefore, if oral anticoagulants are indicated, NOACs rather than warfarin should be considered to lower the risk of fractures. However, further studies are needed to investigate the underlying mechanisms and elucidate causality.

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Clinical Outcome of Edoxaban vs. Vitamin K Antagonists in Patients with Atrial Fibrillation and Diabetes Mellitus: Results from a Multicenter, Propensity-Matched, Real-World Cohort Study

Journal of Clinical Medicine ◽

10.3390/jcm9061621 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1621 ◽

Cited By ~ 1

Author(s):

Vincenzo Russo ◽

Emilio Attena ◽

Anna Rago ◽

Enrico Melillo ◽

Pierpaolo Di Micco ◽

...

Keyword(s):

Diabetes Mellitus ◽

Atrial Fibrillation ◽

Cohort Study ◽

Propensity Score ◽

Incidence Rate ◽

Vitamin K ◽

Real World ◽

Vitamin K Antagonists ◽

Research Database ◽

Thromboembolic Events

Diabetes mellitus (DM) is a chronic metabolic disease which is independently associated with unfavorable clinical outcomes in patients with atrial fibrillation (AF). Few real-world data are available about the clinical performance of non-vitamin K oral anticoagulants (NOACs) among patients with atrial fibrillation and diabetes. The aim of our propensity score-matched cohort study was to compare the safety and effectiveness of Edoxaban versus well-controlled vitamin K antagonists (VKAs) therapy among this population. In this study, we considered patients with AF and diabetes on Edoxaban or VKAs therapy included in the multicenter Atrial Fibrillation Research Database (NCT03760874). The occurrence of major bleedings (MB) and thromboembolic events (a composite of ischemic stroke, transient ischemic attack, systemic embolism) was respectively considered primary safety and effectiveness outcome. We identified 557 AF patients with diabetes who received Edoxaban (n: 230) or VKAs (n: 327) treatment. After propensity score matching analysis, 135 Edoxaban and 135 VKA recipients with similar clinical characteristics were evaluated. The mean follow-up was 27 ± 3 months. The incidence rate of thromboembolic events (TE) was 3.0 per 100 person-years (1.11 in Edoxaban vs. 1.9 in the VKA group, hazard ratio (HR): 0.59; 95% confidence interval (CI), 0.14 to 2.52; p = 0.48). The incidence rate of major bleedings (MB) was 3.7 per 100 person-years (1.2 in Edoxaban vs. 2.7 in the VKA group, HR: 0.43; 95% CI: 0.10 to 1.40; p = 0.14). The incidence rate of intracranial hemorrhage was 0.35 per 100 person-years in Edoxaban vs. 0.74 in the VKA group (HR: 0.49; 95% CI: 0.05 to 5.54; p = 0.56). A positive net clinical benefit (NCB) of Edoxaban over VKAs was found (+1.39). Insulin therapy (HR: 1.76, p = 0.004) and glycated hemoglobin (HR: 1.17, p = 0.002) were found to be independent predictors of TE; moreover, the concomitant use of antiplatelet drugs (HR: 2.41, p = 0.001) was an independent predictor of MB. Conclusions: Our data support the hypothesis of the safety and efficacy of Edoxaban for use in patients with AF and diabetes, justified by a favorable NCB over VKAs.

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