Stroke prevention with non-vitamin K antagonist oral anticoagulants in high risk elderly atrial fibrillation patients at increased bleeding risk

Abstract Background Elderly atrial fibrillation (AF) patients with risk factors of bleeding are often considered ineligible for standard oral anticoagulants (OACs). The ELDERCARE-AF trial recently showed that edoxaban 15mg/day was superior to placebo for preventing stroke or systemic embolism and did not result in a significantly higher incidence of major bleeding. Our aim was to investigate a real-world cohort of AF patients similar to the ELDERCARE-AF cohort, with regard to the impact of non-vitamin K antagonist oral anticoagulant (NOAC) use compared to non-OAC use, in relation to clinical outcomes. Methods From January 1, 2012 to December 31, 2016, 15,183 AF patients aged ≥80 years (mean age 86.63 years [SD 4.79]; 48.7% male) with a CHADS2 score >2 who met the enrollment criteria (generally similar to ELDERCARE-AF) were identified from the Taiwan National Health Insurance Research Database. Patients were categorized into 2 groups according to their stroke prevention strategies, ie. without OACs (n=9,084) and NOACs (n=6,099). Patients receiving NOACs were further stratified into reduced-dose or full-dose regimen groups. Results Compared to the non-OAC group as a reference, NOAC use (whether as reduced dose or full dose) was associated with a lower risk of ischaemic stroke (adjusted hazard ratio [aHR] 0.766, 95% confidence interval [CI] 0.667–0.879) and all-cause mortality (aHR 0.393, 95% CI 0.370–0.418) while the risks of ICH and major bleeding were similar. The risks of composite outcomes of “ischaemic stroke or mortality” (aHR 0.423, 95% CI 0.398–0.449) and “ischaemic stroke or major bleeding or mortality” (aHR 0.490, 95% CI 0.463–0.518) were significantly lower with NOAC use. When compared to non-OAC as the reference groups, NOACs (whether reduced dose or full dose) showed a positive NCB. The results were generally consistent even after the propensity matching (Figure 1). Conclusions In routine clinical care, NOACs (whether reduced or full dose) were associated with a lower risk of ischemic stroke, mortality and the composite endpoint, when compared to non-OAC use in high risk elderly AF patients at increased bleeding risk. Our findings provide complimentary “real world” data to support the generalizability of the results of ELDERCARE-AF trial into daily clinical practice. FUNDunding Acknowledgement Type of funding sources: None. Figure 1

Download Full-text

Non-vitamin K antagonist oral anticoagulants and warfarin in atrial fibrillation patients with concomitant peripheral artery disease

European Heart Journal - Cardiovascular Pharmacotherapy ◽

10.1093/ehjcvp/pvz072 ◽

2019 ◽

Cited By ~ 3

Author(s):

Hsin-Fu Lee ◽

Lai-Chu See ◽

Pei-Ru Li ◽

Jia-Rou Liu ◽

Tze-Fan Chao ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischaemic Stroke ◽

Vitamin K ◽

Major Bleeding ◽

Lower Limb ◽

Lower Risk ◽

Oral Anticoagulants ◽

Vitamin K Antagonist ◽

Peripheral Artery ◽

Artery Disease

Abstract Aims To investigate the effectiveness, safety, and outcomes of lower limb events for non-vitamin K antagonist oral anticoagulants (NOACs) vs. warfarin among atrial fibrillation (AF) patients with concomitant peripheral artery disease (PAD). Methods and results In this nationwide retrospective cohort study collected from Taiwan National Health Insurance Research Database, a total of 5768 and 2034 consecutive AF patients with PAD patients taking NOACs or warfarin were identified from 1 June 2012 to 31 December 2017, respectively. We used propensity score stabilized weighting to balance covariates across study groups. In the cohort, there were 89% patients were taking low-dose NOAC (dabigatran 110 mg twice daily, rivaroxaban 10–15 mg daily, apixaban 2.5 mg twice daily, or edoxaban 30 mg daily). Non-vitamin K antagonist oral anticoagulant was associated with a comparable risk of ischaemic stroke, and a lower risk of acute myocardial infarction [hazard ratio (HR): 0.61, 95% confidence interval (CI): 0.42–0.87; P = 0.007], lower extremity thromboembolism (HR: 0.56, 95% CI: 0.44–0.72; P < 0.0001), revascularization procedure (HR: 0.58, 95% CI: 0.47–0.72; P < 0.0001), lower limb amputation (HR: 0.32, 95% CI: 0.23–0.46; P < 0.0001), and all major bleeding (HR: 0.64, 95% CI: 0.50–0.80; P = 0.0001) than warfarin after weighting. The advantage of NOACs over warfarin persisted in high-risk subgroups including patients of ≥75 years of age, diabetes, renal impairment, or use of concomitant antiplatelet agent. Conclusion This population-based study indicated that NOACs were associated with a comparable risk of ischaemic stroke, and a significantly lower risk of major adverse limb events and major bleeding than warfarin among AF patients with concomitant PAD. Therefore, thromboprophylaxis with NOACs may be considered for such patients.

Download Full-text

GARFIELD-AF model for prediction of stroke and major bleeding in atrial fibrillation: a Danish nationwide validation study

BMJ Open ◽

10.1136/bmjopen-2019-033283 ◽

2019 ◽

Vol 9 (11) ◽

pp. e033283 ◽

Cited By ~ 3

Author(s):

Frederik Dalgaard ◽

Karen Pieper ◽

Freek Verheugt ◽

A John Camm ◽

Keith AA Fox ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischaemic Stroke ◽

Major Bleeding ◽

Risk Model ◽

Oral Anticoagulants ◽

External Validation ◽

Bleeding Risk ◽

Risk Scores ◽

Secondary Outcome

ObjectivesTo externally validate the accuracy of the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) model against existing risk scores for stroke and major bleeding risk in patients with non-valvular AF in a population-based cohort.DesignRetrospective cohort study.SettingDanish nationwide registries.Participants90 693 patients with newly diagnosed non-valvular AF were included between 2010 and 2016, with follow-up censored at 1 year.Primary and secondary outcome measuresExternal validation was performed using discrimination and calibration plots. C-statistics were compared with CHA2DS2VASc score for ischaemic stroke/systemic embolism (SE) and HAS-BLED score for major bleeding/haemorrhagic stroke outcomes.ResultsOf the 90 693 included, 51 180 patients received oral anticoagulants (OAC). Overall median age (Q1, Q3) were 75 (66–83) years and 48 486 (53.5%) were male. At 1-year follow-up, a total of 2094 (2.3%) strokes/SE, 2642 (2.9%) major bleedings and 10 915 (12.0%) deaths occurred. The GARFIELD-AF model was well calibrated with the predicted risk for stroke/SE and major bleeding. The discriminatory value of GARFIELD-AF risk model was superior to CHA2DS2VASc for predicting stroke in the overall cohort (C-index: 0.71, 95% CI: 0.70 to 0.72 vs C-index: 0.67, 95% CI: 0.66 to 0.68, p<0.001) as well as in low-risk patients (C-index: 0.64, 95% CI: 0.59 to 0.69 vs C-index: 0.57, 95% CI: 0.53 to 0.61, p=0.007). The GARFIELD-AF model was comparable to HAS-BLED in predicting the risk of major bleeding in patients on OAC therapy (C-index: 0.64, 95% CI: 0.63 to 0.66 vs C-index: 0.64, 95% CI: 0.63 to 0.65, p=0.60).ConclusionIn a nationwide Danish cohort with non-valvular AF, the GARFIELD-AF model adequately predicted the risk of ischaemic stroke/SE and major bleeding. Our external validation confirms that the GARFIELD-AF model was superior to CHA2DS2VASc in predicting stroke/SE and comparable with HAS-BLED for predicting major bleeding.

Download Full-text

P4780Effectiveness and safety of non-vitamin k antagonist oral anticoagulants in patients with atrial fibrillation and valvular heart disease

European Heart Journal ◽

10.1093/eurheartj/ehz745.1156 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

I K Moon ◽

S R Lee ◽

E K Choi ◽

E J Lee ◽

J H Jung ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Major Bleeding ◽

Lower Risk ◽

Oral Anticoagulants ◽

Vitamin K Antagonist ◽

Composite Outcome ◽

Gi Bleeding ◽

Warfarin Group

Abstract Background Patients with atrial fibrillation (AF) often have concomitant valvular heart disease (VHD), especially in Asia. There are limited data on non-vitamin K antagonist oral anticoagulants (NOAC) impact on outcomes for stroke prevention and bleeding for these patients in real world clinical practice. Purpose To investigate the effectiveness and safety of NOACs compared with warfarin in patients with AF and associated Evaluated Heartvalves, Rheumatic or Artificial (EHRA) type 2 VHD. Methods We identified oral anticoagulants naive patients with AF and EHRA type 2 VHD from the Korean National Health Insurance Service database between 2014 and 2016 (n=2,671 taking warfarin; n=3,058 taking NOAC). Six clinical outcomes including ischemic stroke, intracranial hemorrhage (ICH), gastrointestinal bleeding (GI), major bleeding, all-cause death, and their composite outcome and fatal clinical events (any events that led to death within 30-day of its occurrence) were evaluated. Inverse probability of treatment weighting (IPTW) method was used to balance covariates between the two groups. Results After weighted using 5% trimmed IPTW method (n=2371 taking warfarin; n=2792 taking NOAC), the mean age was 71.2 years, male was 57% and CHA2DS2-VASc score was 3.9. During a mean 1.4-year follow-up, weighted incidence rate of ischemic stroke, ICH, GI bleeding, and all-cause death were lower in the NOAC group than in the warfarin group. Compared to warfarin, 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) and major bleeding (HR 0.61, 95% CI 0.45–0.80). Although NOAC and warfarin groups showed similar incidence rate of ICH, NOAC group was associated with a significantly lower risk of fatal ICH compared to warfarin group (HR 0.28, 95% CI 0.07–0.83). Overall, NOACs were associated with a lower risk of the composite outcome (HR 0.68, 95% CI 0.58–0.80). For an exploratory analysis, patients with EHRA type 1 VHD (n=366 taking warfarin; n=345 taking NOAC) was evaluated. In multivariable Cox regression analysis, NOAC group showed a comparable risk of ischemic stroke, ICH, all-cause death and composite outcome. Clinical outcome in AF patients with VHD Conclusion In this nationwide Asian AF population with EHRA type 2 VHD, NOAC use was associated with lower risks of ischemic stroke, major bleeding, all-cause death, and the composite outcome compared to warfarin.

Download Full-text

Comparison of dabigatran, rivaroxaban, and apixaban for effectiveness and safety in atrial fibrillation: a nationwide cohort study

European Heart Journal - Cardiovascular Pharmacotherapy ◽

10.1093/ehjcvp/pvz086 ◽

2020 ◽

Vol 6 (2) ◽

pp. 75-85 ◽

Cited By ~ 7

Author(s):

Ole-Christian W Rutherford ◽

Christian Jonasson ◽

Waleed Ghanima ◽

Fabian Söderdahl ◽

Sigrun Halvorsen

Keyword(s):

Atrial Fibrillation ◽

Cohort Study ◽

Major Bleeding ◽

Lower Risk ◽

Oral Anticoagulants ◽

Vitamin K Antagonist ◽

Routine Clinical Practice ◽

Systemic Embolism ◽

Nationwide Study ◽

Hazard Ratios

Abstract Aims The aim of this study was to compare the risk of stroke or systemic embolism (SE) and major bleeding in patients with atrial fibrillation (AF) using dabigatran, rivaroxaban, and apixaban in routine clinical practice. Methods and results Using nationwide registries in Norway from January 2013 to December 2017, we established a cohort of 52 476 new users of non-vitamin K antagonist oral anticoagulants (NOACs) with AF. Users of individual NOACs were matched 1:1 on the propensity score to create three pairwise-matched cohorts: dabigatran vs. rivaroxaban (20 504 patients), dabigatran vs. apixaban (20 826 patients), and rivaroxaban vs. apixaban (27 398 patients). Hazard ratios (HRs) for the risk of stroke or SE and major bleeding were estimated. In the propensity-matched comparisons of the risk of stroke or SE, the HRs were 0.88 [95% confidence interval (CI) 0.76–1.02] for dabigatran vs. rivaroxaban, 0.88 (95% CI 0.75–1.02) for dabigatran vs. apixaban, and 1.00 (95% CI 0.89–1.14) for apixaban vs. rivaroxaban. For the risk of major bleeding, the HRs were 0.75 (95% CI 0.64–0.88) for dabigatran vs. rivaroxaban, 1.03 (95% CI 0.85–1.24) for dabigatran vs. apixaban, and 0.79 (95% CI 0.68–0.91) for apixaban vs. rivaroxaban. Conclusion In this nationwide study of patients with AF in Norway, we found no statistically significant differences in risk of stroke or SE in propensity-matched comparisons between dabigatran, rivaroxaban, and apixaban. However, dabigatran and apixaban were both associated with significantly lower risk of major bleeding compared with rivaroxaban.

Download Full-text

Selection, management, and outcome of vitamin K antagonist-treated patients with atrial fibrillation not switched to novel oral anticoagulants

Thrombosis and Haemostasis ◽

10.1160/th15-02-0116 ◽

2015 ◽

Vol 114 (11) ◽

pp. 1076-1084 ◽

Cited By ~ 15

Author(s):

Franziska Michalski ◽

Luise Tittl ◽

Sebastian Werth ◽

Ulrike Hänsel ◽

Sven Pannach ◽

...

Keyword(s):

Atrial Fibrillation ◽

Vitamin K ◽

Major Bleeding ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Case Fatality ◽

Bleeding Risk ◽

Vitamin K Antagonist ◽

Bleeding Complications ◽

Treatment Rate

SummaryAtrial fibrillation (AF) patients treated with well-controlled vitamin K antagonists (VKAs) may benefit less from non-vitamin K antagonist oral anticoagulants (NOACs) because they are supposed to be at low risk of thromboembolic and bleeding complications. However, little is known about the selection, management, and outcome of such “stable” VKA patients in current practice. We assessed characteristics, VKA persistence and 12 months' outcome of AF patients selected for VKA continuation. On March 1, 2013, the Dresden NOAC registry opened recruitment of patients continuing on VKA for sites that had been actively recruiting AF patients treated with NOACs in the prior 18 months. Patient characteristics were compared with those of NOAC patients from the same sites. Four hundred twenty-seven VKA patients had a significantly lower bleeding risk profile compared with 706 patients selected for NOAC treatment. For VKA, international normalised ratio time-in-therapeutic range before enrolment was 71% and increased to 75% during a mean follow-up of 15 months. Rates of stroke/transient ischaemic attack/systemic embolism were 1.3/100 patient-years (intention-to-treat) and 0.94/100 patient-years (as-treated). On-treatment rate of ISTH major bleeding was 4.15/100 patient-years (95% CI 2.60–6.29) with a case-fatality rate of 16.3% (all-cause mortality at day 90 after major bleeding). In conclusion, in daily care, AF patients selected for VKA therapy are healthier than those treated with NOAC, demonstrate a high quality of anticoagulant control and very low stroke rates. However, despite adequate patient selection and INR control, the risk of major VKA bleeding is unacceptably high and bleeding outcome is poor.

Download Full-text

Real-world comparison of major bleeding risk among non-valvular atrial fibrillation patients initiated on apixaban, dabigatran, rivaroxaban, or warfarin

Thrombosis and Haemostasis ◽

10.1160/th16-05-0403 ◽

2016 ◽

Vol 116 (11) ◽

pp. 975-986 ◽

Cited By ~ 104

Author(s):

Allison Keshishian ◽

Shital Kamble ◽

Xianying Pan ◽

Jack Mardekian ◽

Ruslan Horblyuk ◽

...

Keyword(s):

Atrial Fibrillation ◽

Major Bleeding ◽

Real World ◽

Lower Risk ◽

Proportional Hazards ◽

Oral Anticoagulants ◽

Bleeding Risk ◽

Baseline Period ◽

Cox Proportional Hazards ◽

Significant Difference

SummaryIn addition to warfarin, there are four non-vitamin K antagonist oral anticoagulants (NOACs) available for stroke prevention in non valvular atrial fibrillation (NVAF). There are limited data on the comparative risks of major bleeding among newly anticoagulated NVAF patients who initiate warfarin, apixaban, dabigatran, or rivaroxaban, when used in ‘real world’ clinical practice. The study used the Truven MarketScan® Commercial & Medicare supplemental US claims database. NVAF patients aged ≥18 years newly prescribed an oral anticoagulant 01JAN2013–31DEC2014, with a ≥1-year baseline period, were included (study period: 01JAN2012–31DEC2014). Major bleeding was defined as bleeding requiring hospitalisation. Propensity score matching (PSM) was used to balance age, sex, region, baseline comorbidities, and comedications. Cox proportional hazards models were used to estimate the PSM hazard ratio (HR) of major bleeding. Among 45,361 newly anticoagulated NVAF patients, 15,461 (34.1 %) initiated warfarin, 7,438 (16.4 %) initiated apixaban, 17,801 (39.2 %) initiated rivaroxaban, and 4,661 (10.3 %) initiated dabigatran. Compared to matched warfarin initiators, apixaban (HR: 0.53; 95 % CI: 0.39–0.71) and dabigatran (HR: 0.69; 95 % CI: 0.50–0.96) initiators had a significantly lower risk of major bleeding. Patients initiating rivaroxaban (HR: 0.98; 95 % CI: 0.83–1.17) had a non-significant difference in major bleeding risk compared to matched warfarin patients. When comparisons were made between NOACs, matched rivaroxaban patients had a significantly higher risk of major bleeding (HR: 1.82; 95 % CI: 1.36–2.43) compared to apixaban patients. The differences for apixaban-dabigatran and dabigatran-rivaroxaban matched cohorts were not statistically significant. Among newly anticoagulated NVAF patients in the real-world setting, apixaban and dabigatran initiation was associated with significantly lower risk of major bleeding compared to warfarin initiation. When compared to apixaban, rivaroxaban initiation was associated with significantly higher risk of major bleeding.Note: The review process for this paper was fully handled by Christian Weber, Editor in Chief.Supplementary Material to this article is available online at www.thrombosis-online.com.

Download Full-text

Effectiveness and safety of oral anticoagulants in elderly patients with atrial fibrillation

Heart ◽

10.1136/heartjnl-2020-318753 ◽

2021 ◽

pp. heartjnl-2020-318753

Author(s):

Ole-Christian Walter Rutherford ◽

Christian Jonasson ◽

Waleed Ghanima ◽

Fabian Söderdahl ◽

Sigrun Halvorsen

Keyword(s):

Atrial Fibrillation ◽

Elderly Patients ◽

Major Bleeding ◽

Standard Dose ◽

Oral Anticoagulants ◽

Vitamin K Antagonist ◽

Sensitivity Analyses ◽

World Population ◽

Systemic Embolism ◽

Reduced Dose

ObjectivesTo assess the risk of stroke/systemic embolism (SE) and major bleeding associated with the use of oral anticoagulants in elderly patients with atrial fibrillation (AF) in a real-world population.MethodsWe identified all anticoagulant-naive initiators of warfarin, dabigatran, rivaroxaban and apixaban for the indication AF in Norway between January 2013 and December 2017. Multivariate competing risk regression was used to calculate subhazard ratios (SHRs) describing associations between non-vitamin K antagonist oral anticoagulants (NOACs) compared with warfarin for risk of stroke/SE and major bleeding.ResultsAmong 30 401 patients ≥75 years identified (median age 82 years, 53% women, mean CHA2DS2-VaSc score 4.5), 3857 initiated dabigatran, 6108 rivaroxaban, 13 786 apixaban and 6650 warfarin. Reduced dose was initiated in 11 559 (49%) of the NOAC-treated patients. For stroke, the SHRs for standard dose NOAC against warfarin were 0.80 (95% CI 0.57 to 1.13) for dabigatran; 1.07 (95% CI 0.89 to 1.30) for rivaroxaban and 0.95 (95% CI 0.78 to 1.15) for apixaban. For major bleeding, the SHRs against warfarin were 0.75 (95% CI 0.52 to 1.08) for dabigatran; 0.96 (95% CI 0.78 to 1.16) for rivaroxaban and 0.74 (95% CI 0.60 to 0.91) for apixaban. Comparing reduced doses of NOACs with warfarin yielded similar results. Sensitivity analyses were in accordance with the main results.ConclusionIn this nationwide cohort study of patients ≥75 years initiating oral anticoagulation for AF, standard and reduced dose NOACs were associated with similar risks of stroke/SE as warfarin and lower or similar risks of bleeding. The NOACs seem to be a safe option also in elderly patients.

Download Full-text

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.

Download Full-text

Long-term outcomes of Japan-specific dosage of rivaroxaban in high-risk patients with non-valvular atrial fibrillation: analysis from the XAPASS

European Heart Journal ◽

10.1093/ehjci/ehaa946.0646 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

T Ikeda ◽

S Ogawa ◽

T Kitazono ◽

J Nakagawara ◽

K Minematsu ◽

...

Keyword(s):

Atrial Fibrillation ◽

High Risk ◽

Major Bleeding ◽

Factor Xa ◽

Incidence Rates ◽

Funding Source ◽

High Risk Patients ◽

Reduced Dose ◽

Risk Patients

Abstract Background XAPASS is a real-world, prospective, single-arm, observational study conducted as a post-marketing surveillance mandated by the health authority in Japan. Nowadays, direct oral anticoagulant therapy using factor Xa or thrombin inhibitor has been the standard of care for patients with non-valvular atrial fibrillation (NVAF) to prevent ischemic stroke. However, the clinical impact of reduced dosage (approved dose of 15 or 10 mg once daily in Japan is relatively reduced compared to global dosage) factor Xa inhibitor rivaroxaban in high-risk patients remains unclear. Purpose The present sub-analysis of XAPASS was carried out to assess long-term safety and effectiveness of reduced-dose rivaroxaban in high-risk NVAF patients for bleeding and thromboembolism. Methods All patients with NVAF who were newly started on rivaroxaban were eligible for surveillance. The principal safety outcome was a composite of major and non-major bleeding events, and the primary effectiveness outcome was a composite of ischaemic stroke, haemorrhagic stroke, non-central nervous system systemic embolism (non-CNS SE), and myocardial infarction (MI). In this present sub-analysis, high-risk patients were defined as those who had two of the following three risk factors: elderly (≥75 years old), low body weight (≤50 kg), and renal impairment (CrCl <50 mL/min). Results In total, 11,308 patients were enrolled between April 2012 and June 2014 from 1,419 hospitals, and overall data were analysed from 10,664 patients from whom data were collected. Among them, 3,694 patients matched the criteria for the high-risk patients defined in this sub-analysis, and 6,970 patients did not match the criteria (non-high-risk patients). The mean treatment duration was 791±673 days in the high-risk patients and 944±709 days in the non-high-risk patients. Mean patient age was 80.9±5.5 years and 69.0±9.0 years at baseline, respectively. Mean CHADS2 score was 2.8 and 1.8, and CHA2DS2-VASc score was 4.4 and 2.9, respectively. The rates of CHADS2 component comorbidities were lower in the non-high-risk patients except for diabetes mellitus. The incidence rates of any bleeding, major bleeding, and the primary effectiveness outcomes were 4.8, 1.6, and 2.1%/patient-year in the high-risk patients. The incidence rates of these clinical events in the non-high-risk patients were 3.3, 0.9, and 1.0%/patient-year, respectively. Conclusions Incidence rates of long-term bleeding and thromboembolism were higher in the high-risk patients than in the non-high-risk patients. However, the rates of these outcomes using the Japan-specific reduced dose were not so high. Furthermore, the balance between safety and effectiveness outcomes was within an acceptable range. The present study provides useful information for physicians to stratify high-risk patients using the reduced dose in daily clinical practice. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Bayer Yakuhin Ltd.

Download Full-text

Non–Vitamin K Antagonist Oral Anticoagulants in the Treatment of Atrial Fibrillation

Annual Review of Medicine ◽

10.1146/annurev-med-042617-092334 ◽

2019 ◽

Vol 70 (1) ◽

pp. 61-75 ◽

Cited By ~ 3

Author(s):

Alexander C. Fanaroff ◽

E. Magnus Ohman

Keyword(s):

Atrial Fibrillation ◽

Vitamin K ◽

Major Bleeding ◽

Anticoagulant Activity ◽

Oral Anticoagulants ◽

Significant Risk ◽

Vitamin K Antagonist ◽

Therapeutic Window ◽

Mechanical Valves ◽

Frequent Monitoring

Atrial fibrillation (AF) increases a patient's stroke risk four- to five-fold. Anticoagulation with the vitamin K antagonist (VKA) warfarin reduces the risk of stroke by 67%, but warfarin carries a significant risk of major bleeding and has unpredictable pharmacodynamics with a narrow therapeutic window, necessitating frequent monitoring of its anticoagulant effect. The non–vitamin K antagonist oral anticoagulants (NOACs) dabigatran, rivaroxaban, apixaban, and edoxaban provide more predictable anticoagulant activity than warfarin with a lower risk of major bleeding, and each is noninferior to warfarin for the prevention of stroke. All have earned regulatory approval in the past eight years. At least one of the NOACs is approved for use in all patients with AF, except those with mechanical valves and rheumatic mitral valve disease, for whom warfarin remains the only option. Recent clinical trials have shown that antithrombotic regimens including NOACs are safe and effective in patients with AF who need potent antiplatelet therapy.

Download Full-text