Abstract 19119: Concomitant Use of Antiplatelet Therapy with Edoxaban or Warfarin in Patients with Atrial Fibrillation in the ENGAGE AF-TIMI 48 Trial

BACKGROUND: Patients with atrial fibrillation (AF) who receive both antiplatelet (AP) and anticoagulant therapy are at markedly higher risk of bleeding. The ENGAGE AF-TIMI 48 trial showed that both the high- (HD) and low-dose (LD) regimens of the once-daily factor Xa inhibitor edoxaban (Edox) were as effective as well-managed warfarin (Warf) (median TTR 68.4%) in preventing stroke or systemic embolism (SEE) with significant reductions in major bleeding and cardiovascular mortality. In this study, we assessed the relative efficacy and safety of Edox as compared with Warf in patients with and without concomitant use of AP therapy. METHODS: This was a randomized, double-blind, double-dummy trial comparing HD (60 mg daily, reduced to 30mg in patients with anticipated increased drug exposure) and LD (30 mg daily, reduced to 15mg) Edox with Warf. Dual AP therapy was prohibited while receiving study drug. Cox proportional hazards models were performed stratified by AP use at 3 months with treatment as a covariate. RESULTS: Of the 21,105 patients, 4,912 (23%) were receiving AP therapy at 3 months (92% aspirin). Patients who received concomitant AP therapy had higher rates of major bleeding compared to patients who did not (Fig). Both Edox regimens had similar relative efficacy in preventing stroke or SEE compared with Warf regardless of concomitant AP use (P int >0.10 for both) with consistent reductions in major bleeding (HD Edox vs. Warf: P int =0.91; LD Edox vs. Warf: P int =0.59). In patients randomized to LD Edox, AP therapy was associated with a further reduction in the net clinical outcome of death, stroke, SEE, or major bleeding (P int =0.02) compared with Warf. CONCLUSIONS: Regardless of concomitant AP therapy, both doses of Edox significantly reduced bleeding compared to well-managed Warf. The safety profile of Edox may be particularly attractive in patients with AF who receive a combination of AP and anticoagulant therapy because of higher absolute risk of bleeding.

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Burden of major gastrointestinal bleeding among oral anticoagulant-treated non-valvular atrial fibrillation patients

Therapeutic Advances in Gastroenterology ◽

10.1177/1756284821997352 ◽

2021 ◽

Vol 14 ◽

pp. 175628482199735

Author(s):

Steven Deitelzweig ◽

Allison Keshishian ◽

Amiee Kang ◽

Amol D. Dhamane ◽

Xuemei Luo ◽

...

Keyword(s):

Atrial Fibrillation ◽

Major Bleeding ◽

Oral Anticoagulant ◽

Proportional Hazards ◽

Bleeding Event ◽

Cox Proportional Hazards ◽

High Rate ◽

Gi Bleeding ◽

Increased Risk ◽

Gi Bleed

Background: Gastrointestinal (GI) bleeding is the most common type of major bleeding associated with oral anticoagulant (OAC) treatment. Patients with major bleeding are at an increased risk of a stroke if an OAC is not reinitiated. Methods: Non-valvular atrial fibrillation (NVAF) patients initiating OACs were identified from the Centers for Medicare and Medicaid Services ( CMS) Medicare data and four US commercial claims databases. Patients who had a major GI bleeding event (hospitalization with primary diagnosis of GI bleeding) while on an OAC were selected. A control cohort of patients without a major GI bleed during OAC treatment was matched to major GI bleeding patients using propensity scores. Stroke/systemic embolism (SE), major bleeding, and mortality (in the CMS population) were examined using Cox proportional hazards models with robust sandwich estimates. Results: A total of 15,888 patients with major GI bleeding and 833,052 patients without major GI bleeding were included in the study. Within 90 days of the major GI bleed, 58% of patients discontinued the initial OAC treatment. Patients with a major GI bleed had a higher risk of stroke/SE [hazard ratio (HR): 1.57, 95% confidence interval (CI): 1.42–1.74], major bleeding (HR: 2.79, 95% CI: 2.64–2.95), and all-cause mortality (HR: 1.29, 95% CI: 1.23–1.36) than patients without a major GI bleed. Conclusion: Patients with a major GI bleed on OAC had a high rate of OAC discontinuation and significantly higher risk of stroke/SE, major bleeding, and mortality after hospital discharge than those without. Effective management strategies are needed for patients with risk factors for major GI bleeding.

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Effectiveness and safety of apixaban versus warfarin in non-valvular atrial fibrillation patients in “real-world” clinical practice

Thrombosis and Haemostasis ◽

10.1160/th17-01-0068 ◽

2017 ◽

Vol 117 (06) ◽

pp. 1072-1082 ◽

Cited By ~ 69

Author(s):

Xiaoyan Li ◽

Steve Deitelzweig ◽

Allison Keshishian ◽

Melissa Hamilton ◽

Ruslan Horblyuk ◽

...

Keyword(s):

Atrial Fibrillation ◽

Major Bleeding ◽

Real World ◽

Proportional Hazards ◽

Significant Risk ◽

Haemorrhagic Stroke ◽

Cox Proportional Hazards ◽

Kaplan Meier ◽

Cox Proportional Hazards Models ◽

Warfarin Treatment

SummaryThe ARISTOTLE trial showed a risk reduction of stroke/systemic embolism (SE) and major bleeding in non-valvular atrial fibrillation (NVAF) patients treated with apixaban compared to warfarin. This retrospective study used four large US claims databases (MarketScan, PharMetrics, Optum, and Humana) of NVAF patients newly initiating apixaban or warfarin from January 1, 2013 to September 30, 2015. After 1:1 warfarin-apixaban propensity score matching (PSM) within each database, the resulting patient records were pooled. Kaplan-Meier curves and Cox proportional hazards models were used to estimate the cumulative incidence and hazard ratios (HRs) of stroke/SE and major bleeding (identified using the first listed diagnosis of inpatient claims) within one year of therapy initiation. The study included a total of 76,940 (38,470 warfarin and 38,470 apixaban) patients. Among the 38,470 matched pairs, 14,563 were from MarketScan, 7,683 were from PharMetrics, 7,894 were from Optum, and 8,330 were from Humana. Baseline characteristics were balanced between the two cohorts with a mean (standard deviation [SD]) age of 71 (12) years and a mean (SD) CHA2DS2-VASc score of 3.2 (1.7). Apixaban initiators had a significantly lower risk of stroke/SE (HR: 0.67, 95 % CI: 0.59–0.76) and major bleeding (HR: 0.60, 95 % CI: 0.54–0.65) than warfarin initiators. Different types of stroke/SE and major bleeding – including ischaemic stroke, haemorrhagic stroke, SE, intracranial haemorrhage, gastrointestinal bleeding, and other major bleeding – were all significantly lower for apixaban compared to warfarin treatment. Subgroup analyses (apixaban dosage, age strata, CHA2DS2-VASc or HAS-BLED score strata, or dataset source) all show consistently lower risks of stroke/SE and major bleeding associated with apixaban as compared to warfarin treatment. This is the largest “real-world” study on apixaban effectiveness and safety to date, showing that apixaban initiation was associated with significant risk reductions in stroke/SE and major bleeding compared to warfarin initiation after PSM. These benefits were consistent across various high-risk subgroups and both the standard-and low-dose apixaban dose regimens.Note: The review process for this manuscript was fully handled by Christian Weber, Editor in Chief.Supplementary Material to this article is available online at www.thrombosis-online.com.

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Abstract 17617: History of Bleeding and Outcomes with Apixaban versus Warfarin in Patients with Atrial Fibrillation in the ARISTOTLE Trial

Circulation ◽

10.1161/circ.130.suppl_2.17617 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Raffaele De Caterina ◽

Ulrika Andersson ◽

John H Alexander ◽

M.Cecilia Bahit ◽

Patrick J Commerford ◽

...

Keyword(s):

Atrial Fibrillation ◽

Body Weight ◽

Major Bleeding ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Channel Blockers ◽

Chads2 Score ◽

History Of

Background: History of bleeding is important in decisions for anticoagulation. We analyzed outcomes in relation to history of bleeding and randomized treatments in patients with atrial fibrillation (AF) in the ARISTOTLE trial. Methods: The on-treatment safety population included 18,140 patients receiving ≥1 dose of study drug, apixaban 5 mg bd (2.5 mg bd if 2 of the following: age >80 yrs; body weight <60 kg; or creatinine >133 μmol/L) or warfarin aiming for INR 2.0-3.0 (median TTR 66%), for a median of 1.8 yrs. Adjudicated outcomes in relation to randomization and history of bleeding were analyzed using a Cox proportional hazards model. Efficacy endpoints were analyzed in the intention-to-treat population. Results: A history of bleeding was reported in 3033 patients (16.7%), who more often were male (68% vs 64%, p <0.0005); with a history of prior stroke/TIA/systemic embolism (23% vs 19%, p <0.0001); diabetes (27% vs 24%, p=0.0010); higher CHADS2 score (CHADS2 >3: 35% vs 29%), age (mean [SD] 71 [9] vs 69 [10], p <0001) and body weight (86 [21] vs 84 [21], p <0.0001); lower creatinine clearance (77 [33] vs 80 [33], p=0.0007) and mean systolic blood pressure (131 [17] vs 132 [16], p=0.0027). Calcium channel blockers, statins, non-steroidal anti-inflammatory drugs and proton pump inhibitors were used more often in patients with vs without a history of bleeding. Major bleeding was the only outcome event occurring more frequently in patients with vs without a history of bleeding, HR 1.7 (95% CI 1.4-2.3) with apixaban and 1.5 (1.2-1.0) with warfarin. Primary efficacy and safety outcomes in relation to randomization, see Table. Conclusions: In patients with AF, a history of bleeding was associated with several risk factors for stroke and bleeding and, accordingly, a higher bleeding risk during anticoagulation. Benefits with apixaban vs warfarin as to stroke, mortality and major bleeding, are however consistent irrespective of bleeding history.

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Abstract 15467: Impact of Thrombocytopenia on Clinical Outcomes in Atrial Fibrillation Patients With Anemia: The Fushimi Af Registry

Circulation ◽

10.1161/circ.142.suppl_3.15467 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Kenjiro Ishigami ◽

Syuhei Ikeda ◽

KOSUKE DOI ◽

Yasuhiro Hamatani ◽

Akiko Fujino ◽

...

Keyword(s):

Atrial Fibrillation ◽

Clinical Outcomes ◽

Major Bleeding ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Antithrombotic Drugs ◽

Prospective Survey ◽

Kaplan Meier ◽

Significant Difference ◽

Independent Determinant

Introduction: Anemia has been reported to be associated with poor prognosis in patients with atrial fibrillation (AF). Concomitant thrombocytopenia (TP) may or may not affect the prescription of antithrombotic drugs and clinical outcomes in these patients. Methods: The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Kyoto. We defined TP as platelet counts less than 150,000/μL and anemia as hemoglobin less than 11 g/dL. Among 666 patients with anemia, we compared the clinical backgrounds and outcomes of those with TP (n=183) and those without (n=483). Results: Compared with patients without TP, patients with TP were more likely to have chronic kidney disease (75.4% vs. 61.8%, p=0.001), and less likely to have hypertension (58.5% vs. 67.0%, p=0.0393), and less likely to have dyslipidemia (27.3% vs. 38.3%, p=0.0079). Age, sex, body weight, CHADS 2 score, CHA 2 DS 2 -VASc score, HAS-BLED score, and previous major bleeding were comparable between the groups. Furthermore, prescription of anti-thrombotic drugs was comparable (Figure A). On Kaplan-Meier analysis, the incidence of all-cause death was higher in TP group (hazard ratio [HR] 1.52; 95% confidence interval [CI] 1.20-1.91, p<0.05) (Figure B-1). There was no significant difference in other adverse events between patients with and without TP (major bleeding: HR 1.11; 95% CI 0.41-3.31, p=0.8, hospitalization for heart failure: HR 1.11; 95% CI 0.74-1.61, p= 0.61 and stroke or systemic embolism: HR 0.91; 95% CI 0.43-1.78, p=0.80) (Figure B-2, 3, 4). Multivariate Cox proportional hazards regression analysis adjusting for potential confounders revealed that TP was an independent determinant of all-cause death (adjusted HR: 1.41, 95% CI; 1.11-1.78, p=0.006). Conclusions: Concomitant TP in AF patients with anemia did not affect the prescription of antithrombotic drugs, and was independently associated with all-cause death in the Fushimi AF Registry.

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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.

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Abstract 16866: Blood Pressure Control and Stroke or Bleeding Risk in Patients with Atrial Fibrillation: Results from the ROCKET AF Trial

Circulation ◽

10.1161/circ.130.suppl_2.16866 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Sreekanth Vemulapalli ◽

Anne S Hellkamp ◽

W. Schuyler Jones ◽

Jonathan P Piccini ◽

Kenneth W Mahaffey ◽

...

Keyword(s):

Atrial Fibrillation ◽

Blood Pressure ◽

Major Bleeding ◽

Hemorrhagic Stroke ◽

Proportional Hazards ◽

Bleeding Risk ◽

Cox Proportional Hazards ◽

Adjusted Risk ◽

History Of ◽

Stage 1

Background: Hypertension (HTN) is a risk factor for stroke and bleeding in atrial fibrillation (AF). Yet, the association between HTN stage and stroke and bleeding risk in AF is unknown. Methods: The study population included 14,256 of the patients randomized in the ROCKET AF trial. Baseline systolic blood pressure (SBP) and history of HTN were determined and categorized as follows: (1) no history of HTN, (2) controlled HTN (SBP <140), (3) stage 1 HTN (SBP 140-159), and (4) stage 2 HTN (SBP ≥160). Cox proportional hazards models were used to compare event rates for stroke or systemic embolism (SE) and major bleeding. Results: Of the 90.5% of patients in ROCKET AF with HTN, 55.9% were controlled and 34.6% had stage 1 or 2 HTN. Compared with those with HTN, those without HTN had lower mean CHADS 2 scores (2.8 vs. 3.5), lower rates of prior myocardial infarction (11% vs. 18%), and lower mean age (69 vs. 73 years). Compared with those with no history of HTN, there was a trend towards an increased adjusted risk of stroke or SE in patients with controlled HTN (HR 1.22, 95% CI 0.89-1.66) and stage 1 or 2 HTN (HR 1.42, 95% CI 1.03-1.95) (p=0.06). A similar trend in adjusted risk of hemorrhagic stroke (controlled HTN: HR 2.50, 95% CI 0.89-7.05; stage 1 or 2 HTN: HR 3.04, 95% CI 1.06-8.71) (p=0.11) was observed. The effect of HTN stage on stroke risk did not vary by baseline CHADS 2 score (p interaction=0.70). The adjusted risk of major bleeding was not different between groups (HR 0.96, 95% CI 0.74-1.23; HR 1.00, 95% CI 0.77-1.30) (p=0.84). The benefit of rivaroxaban versus warfarin in preventing stroke or SE was consistent among patients regardless of baseline SBP (p interaction=0.69). Conclusion: One-third of patients in a clinical trial of AF had uncontrolled SBP at baseline. Uncontrolled SBP showed a trend towards a higher risk of stroke or SE, but not bleeding. Uncontrolled SBP may be an important factor in reducing the overall risk of stroke, and specifically hemorrhagic stroke, in patients with AF.

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A comparison of the safety and effectiveness of dabigatran and warfarin in non-valvular atrial fibrillation patients in a large healthcare system

Thrombosis and Haemostasis ◽

10.1160/th15-06-0453 ◽

2015 ◽

Vol 114 (12) ◽

pp. 1290-1298 ◽

Cited By ~ 76

Author(s):

Janet Schnee ◽

Kathy Fraeman ◽

Kimberly Siu ◽

Matthew W. Reynolds ◽

Jenna Collins ◽

...

Keyword(s):

Atrial Fibrillation ◽

Clinical Practice ◽

Major Bleeding ◽

Proportional Hazards ◽

Clinical Care ◽

Cox Proportional Hazards ◽

Gi Bleeding ◽

Bleeding Events ◽

Nonvalvular Atrial Fibrillation ◽

Lower Gi Bleeding

SummaryDabigatran is approved for stroke risk reduction in patients with nonvalvular atrial fibrillation (NVAF). Data from diverse clinical practice settings will help establish whether the risk:benefit ratio seen in clinical trials is comparable with routine clinical care. This study aimed to compare the safety and effectiveness of dabigatran and warfarin in clinical practice. We undertook a propensity score-matched (PSM) cohort study (N=12,793 per group; mean age 74) comparing treatment with dabigatran or warfarin in the US Department of Defense claims database, October 2009 to July 2013. Treatment-naïve patients with first prescription claim for dabigatran (either FDA-approved dose) or warfarin between October 2010 and July 2012 (index) and a diagnosis of NVAF during the 12 months before index date were included. Primary outcomes were stroke and major bleeding. Secondary outcomes included ischaemic and haemorrhagic stroke, major gastrointestinal (GI), urogenital or other bleeding, myocardial infarction (MI) and death. Time-to-event was investigated using Kaplan-Meier survival analyses. Outcomes comparisons were made utilising Cox-proportional hazards models of PSM groups. Dabigatran users experienced fewer strokes (adjusted hazard ratio [95 % confidence intervals] 0.73 [0.55–0.97]), major intracranial (0.49 [0.30–0.79]), urogenital (0.36 [0.18–0.74]) and other (0.38 [0.22–0.66]) bleeding, MI (0.65 [0.45–0.95]) and deaths (0.64 [0.55–0.74]) than the warfarin group. Major bleeding (0.87 [0.74–1.03]) and major GI bleeding (1.13 [0.94–1.37]) was similar between groups and major lower GI bleeding events were more frequent (1.30 [1.04–1.62]) with dabigatran. In conclusion, compared with warfarin, dabigatran treatment was associated with a lower risk of stroke and most outcomes measured, but increased incidence of major lower GI bleeding.

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3051Effectiveness and safety of apixaban, dabigatran and warfarin compared to rivaroxaban in non-valvular atrial fibrillation; a Norwegian nationwide cohort study

European Heart Journal ◽

10.1093/eurheartj/ehz745.0018 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

O.-C.W Rutherford ◽

C J Jonasson ◽

W G Ghanima ◽

S H Halvorsen

Keyword(s):

Atrial Fibrillation ◽

Cohort Study ◽

Major Bleeding ◽

Proportional Hazards ◽

Standard Dose ◽

Oral Anticoagulants ◽

Real Life ◽

Group Versus ◽

Cox Proportional Hazards ◽

Prescription Database

Abstract Introduction Non-vitamin K oral anticoagulants (NOACs) are increasingly used for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). Although proven effective and safe, there is limited knowledge of the comparative effectiveness and safety of the different NOACs in real life. Norway has nationwide registries of good quality, being suitable for doing such a comparison. Purpose The aim of this nationwide cohort study was to compare the risk of stroke/systemic embolism (SE) and major bleeding in patients with NVAF treated with dabigatran, apixaban and warfarin compared with patients treated with rivaroxaban. Methods By merging nationwide registries (the Norwegian Patient Registry and the Norwegian Prescription Database), a cohort was created including all oral anticoagulant (OAC)-naïve adult NVAF patients initiating OAC in the study period 1 Jan 2013 to 31 Dec 2017. The patients were followed until switching of OAC type, discontinuation, death, or end of study-period. Cox proportional-hazards regression was used to estimate adjusted hazard ratios (HRs) for the risk of stroke/SE or bleeding in patients using dabigatran, apixaban and warfarin compared to rivaroxaban. Results A total of 65 563 new users of OAC were included; 10,413 initiated dabigatran, 28,363 apixaban, 13,087 warfarin and 13,700 rivaroxaban. The median age was 71 yrs for dabigatran, 74 yrs for apixaban, 75 yrs for warfarin, and 73 yrs for rivaroxaban; 58.3% were men. Dabigatran-users were younger and had less comorbidities than all other OAC-users; the greatest difference was in the proportion with chronic kidney disease (2.4% in the dabigatran-group versus 7.0%, 12.5%, and 4.6% in the apixaban, warfarin and rivaroxaban groups, respectively). During a median follow-up time of 14.7 months (IQR 4.9–30.6), 2 361 (3.6%) patients suffered a stroke/SE, 2,051 (3.1%) had a major bleeding, and 4 250 (6.5%) died. Adjusted HRs for stroke/SE and major bleeding are presented in the figure. When the risk of stroke/SE and major bleeding was assessed solely in patients that received the standard dose of OAC (73% of NOAC users), the results were similar to the results for the entire population. OACs compared to rivaroxaban Conclusion In this nationwide cohort study of patients with NVAF being new users of OAC, we found no significant differences in risk of stroke/SE between different OACs and rivaroxaban, whereas dabigatran and apixaban were associated with significantly lower risk of major bleeding. Acknowledgement/Funding The study was funded by the South-Eastern Norway Regional Health Authority, and by BMS/Pfizer through the ERISTA program.

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Abstract 16398: Comparison of Major Bleeding Risk and Associated Costs Among Newly Anticoagulated Non-valvular Atrial Fibrillation Patients

Circulation ◽

10.1161/circ.132.suppl_3.16398 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Steven Deitelzweig ◽

Amanda Bruno ◽

Natalie Tate ◽

Augustina Ogbonnaya ◽

Manan Shah ◽

...

Keyword(s):

Atrial Fibrillation ◽

Major Bleeding ◽

Real World ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Oral Anticoagulants ◽

Bleeding Risk ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Hazards Model

Real-world evidence highlighting the risks and benefits of novel oral anticoagulants (NOCAs) is lacking. This study compared major and clinically relevant non-major (CRNM) bleeding risk and costs among non-valvular atrial fibrillation (NVAF) patients newly treated with apixaban, dabigatran, rivaroxaban, or warfarin. A retrospective analysis of NVAF patients newly treated with apixaban, dabigatran, rivaroxaban, or warfarin was conducted using PharMetrics Plus data from 1/ 2012 - 9/ 2014. Patients were indexed on the date of the first anticoagulant prescription, and were required to be ≥18 years old and have CHA 2 DS 2 -VASc score > 0 and ≥ 1 month of follow-up. Patients were followed until discontinuation (≥30-day gap in treatment), treatment switch, end of continuous enrollment, 1 year post-index, or end of study. Major and CRNM bleeding, and bleeding-related costs were measured. Cox proportional hazards model was used to examine the association between anticoagulants and risk of bleeding and GLM was used to evaluate bleeding-related costs. The study included 24,573 NVAF patients; distributed as apixaban 11.7%, dabigatran 12.0%, rivaroxaban 36.7%, and warfarin 39.6%. Mean age was 64.4 and 66.5% were males. HAS-BLED and CHA 2 DS 2 -VASc scores averaged 2.0 and 2.7, respectively. After adjusting for differences in baseline characteristics, when compared to apixaban patients, rivaroxaban (HR: 1.5; P =0.0013) and warfarin (HR: 1.7; P <0.0001) patients were more likely to have major bleeding, and dabigatran (HR: 1.3; P =0.0030), rivaroxaban (HR: 1.7; P <0.0001), and warfarin (HR: 1.4; P <0.0001) patients were more likely to have CRNM bleeding. Major bleeding risk was similar between apixaban and dabigatran patients. Major and CRNM bleeding costs, when compared to apixaban patients ($154 and $18), were significantly higher for dabigatran ($457; P <0.0001 and $39; P <0.0001), rivaroxaban ($420; P <0.0001 and $61; P <0.0001), and warfarin ($511; P <0.0001 and $63; P <0.0001) patients. Among anticoagulant-naive moderate-to-high risk NVAF patients encountered in real-world clinical setting, major bleeding was lower with apixaban compared to warfarin and rivaroxaban. Bleeding costs were lower with apixaban compared to alternative NOACs and warfarin.

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Risks and Benefits of Direct Oral Anticoagulants across the Spectrum of GFR among Incident and Prevalent Patients with Atrial Fibrillation

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.13811217 ◽

2018 ◽

Vol 13 (8) ◽

pp. 1144-1152 ◽

Cited By ~ 17

Author(s):

Jung-Im Shin ◽

Alex Secora ◽

G. Caleb Alexander ◽

Lesley A. Inker ◽

Josef Coresh ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Oral Anticoagulant ◽

Proportional Hazards ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Cox Proportional Hazards ◽

Direct Oral Anticoagulant ◽

Bleeding Events ◽

Risk Of Bleeding

Background and objectivesAll randomized trials of direct oral anticoagulants in atrial fibrillation excluded patients with severe kidney disease. The safety and effectiveness of direct oral anticoagulants across the range of eGFR in real-world settings is unknown. Our objective is to quantify the risk of bleeding and benefit of ischemic stroke prevention for direct oral anticoagulants compared with warfarin in patients with atrial fibrillation with and without CKD.Design, setting, participants, & measurementsWe created a propensity score–matched cohort of 3206 patients with atrial fibrillation and direct oral anticoagulant use and 3206 patients with atrial fibrillation using warfarin from October of 2010 to February of 2017 in an electronic health record (Geisinger Health System). The risks of bleeding and ischemic stroke were compared between direct oral anticoagulant and warfarin users using Cox proportional hazards regression, stratified by eGFR (≥60 and <60 ml/min per 1.73 m2).ResultsThe mean (SD) age of the 6412 participants was 72 (12) years, 47% were women, and average eGFR was 69 (21) ml/min per 1.73 m2. There were 1181 bleeding events and 466 ischemic strokes over 7391 person-years of follow-up. Compared with warfarin use, the hazard ratios (HRs) (95% confidence interval [95% CI]) of bleeding associated with direct oral anticoagulant use were 1.01 (0.88 to 1.17) and 1.23 (1.02 to 1.48) for those with eGFR≥60 and eGFR<60 ml/min per 1.73 m2, respectively (P-interaction=0.10). There was no difference between direct oral anticoagulant and warfarin users in the risk of ischemic stroke: HRs (95% CI) of 0.94 (0.74 to 1.18) and 1.02 (0.76 to 1.37) for those with eGFR≥60 and eGFR<60 ml/min per 1.73 m2, respectively (P-interaction=0.70). Similar findings were observed with individual drugs.ConclusionsIn a large health care system, patients with eGFR<60 ml/min per 1.73 m2 who took direct oral anticoagulants for atrial fibrillation had slightly higher risk of bleeding compared with those on warfarin, but similar benefits from prevention of ischemic stroke.

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