Dabigatran in real-world atrial fibrillation

2016 ◽  
Vol 116 (10) ◽  
pp. 754-763 ◽  
Author(s):  
Francisco Moscoso Costa ◽  
Jorge Ferreira ◽  
Miguel Mendes ◽  
João Carmo
Keyword(s):  
Myocardial Infarction ◽  
Atrial Fibrillation ◽  
Ischaemic Stroke ◽  
Major Bleeding ◽  
Real World ◽  
Vitamin K Antagonists ◽  
Intracranial Bleeding ◽  
Gi Bleeding ◽  
Stroke Incidence ◽  
Significant Difference

SummaryIn the RE-LY clinical trial, dabigatran presented a better effectiveness/ safety profile when compared to warfarin. However, clinical trials are not very representative of the real-world setting. We aimed to assess the performance of dabigatran in real-world patients with atrial fibrillation (AF) by means of a systematic review and meta-analysis of observational comparison studies with vitamin K antagonists (VKA). We searched PubMed, Embase and Scopus databases until November 2015 and selected studies according to the following criteria: observational study performed with nonvalvular AF patients; reporting adjusted hazard ratios (HR) of clinical events in a follow-up period; for dabigatran 75 mg, 110 mg or 150 mg versus VKA. Twenty studies were selected which included 711,298 patients, 210,279 of which were treated with dabigatran and the remaining 501,019 with VKA. Ischaemic stroke incidence was of 1.65 /100 patient-years for dabigatran and 2.85/100 patient-years for VKA (HR 0.86, 95 % confidence interval of 0.74–0.99). Major bleeding rate was 3.93/100 patient-years for dabigatran and 5.61/100 patient-years for VKA (0.79, 0.69–0.89). Risk of mortality (0.73, 0.61–0.87) and intracranial bleeding (0.45, 0.38–0.52) were significantly lower in patients treated with dabigatran when compared to patients on VKA. Risk of gastrointestinal (GI) bleeding was significantly higher in patients treated with dabigatran (1.13, 1.00–1.28). No significant difference was observed in risk of myocardial infarction (0.99, 0.89–1.11). In this combined analysis of real-world observational comparison studies with VKA, dabigatran was associated with a lower risk of ischaemic stroke, major bleeding, intracranial bleeding and mortality, higher risk of GI bleeding and a similar risk of myocardial infarction.Supplementary Material to this article is available online at www.thrombosis-online.com.

Abstract 12465: Dabigatran in Real World of Atrial Fibrillation: Systematic Review and Meta-analysis of Comparison Studies With Vitamin K Antagonists

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
João Carmo ◽  
Francisco M Costa ◽  
Jorge Ferreira ◽  
Miguel Mendes
Keyword(s):  
Myocardial Infarction ◽  
Atrial Fibrillation ◽  
Systematic Review ◽  
Intracranial Hemorrhage ◽  
Vitamin K ◽  
Major Bleeding ◽  
Real World ◽  
Observational Studies ◽  
Meta Analysis ◽  
Vitamin K Antagonists

Background: In the clinical trial RE-LY, dabigatran showed a better efficacy/safety profile in comparison with warfarin, but clinical trials are few representative of the real world. We aim to access if dabigatran in real-world patients with atrial fibrillation (AF) showed a better profile in comparison with warfarin, through a systematic review and meta-analysis of observational studies comparing with vitamin K antagonists. Methods: PubMed, Embase and Scopus databases were searched through December 2014. We include observational studies comparing dabigatran to warfarin for non-valvular AF that reported clinical events during a follow-up for dabigatran 75mg, 110 mg or 150 mg, and warfarin. We proceeded to the extraction and analysis of data for clinical thromboembolic events, bleeding and mortality. Data were pooled by meta-analysis using a random-effects model. Results: We selected 9 studies involving a total of 291,703 patients, 85,399 treated with dabigatran and the remaining 206,304 with warfarin. The incidence of stroke was 1.71 / 100 patient-years for dabigatran and 2.44 / 100 patient years for warfarin (relative risk [RR] 0.91, 95% CI 0.66 to 1.27, p=0.58). The major bleeding rate was 3.90 / 100 patient-years for dabigatran and 3.92 / 100 patient years for warfarin (RR 0.90; 0.78 to 1.03, p=0.11). The all-cause mortality (RR 0.81, 0.75-0.88, p<0.001) and intracranial hemorrhage (RR 0.45, from 0.27 to 0.76, p=0.002) were significantly lower in patients treated with dabigatran in comparison to those treated with warfarin. There were no significant differences in risk of myocardial infarction (RR 0.55; 0.29 to 1.07, p=0.08), total hemorrhage (RR 1.00; 0.57 to 1.77, p=0.99), and gastro-intestinal bleeding (RR 1.14; 0.78 to 1.69, p=0.50). Conclusions: In this combined analysis of observational studies of real world, dabigatran compared to warfarin was associated with a similar risk of stroke, myocardial infarction, major bleeding, total bleeding and gastrointestinal bleeding, and a lower risk of intracranial hemorrhage and mortality.

scholarly journals Effectiveness and Safety of Direct Oral Anticoagulants versus Vitamin K Antagonists for People Aged 75 Years and over with Atrial Fibrillation: A Systematic Review and Meta-Analyses of Observational Studies

2019 ◽  
Vol 8 (4) ◽  
pp. 554 ◽  
Author(s):  
Anneka Mitchell ◽  
Margaret C. Watson ◽  
Tomas Welsh ◽  
Anita McGrogan
Keyword(s):  
Myocardial Infarction ◽  
Atrial Fibrillation ◽  
Ischaemic Stroke ◽  
Major Bleeding ◽  
Observational Studies ◽  
Intracranial Haemorrhage ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Significant Difference ◽  
Meta Analyses

Older people, are underrepresented in randomised controlled trials of direct oral anticoagulants (DOACs) for stroke prevention in atrial fibrillation (AF). The aim of this study was to combine data from observational studies to provide evidence for the treatment of people aged ≥75 years. Medline, Embase, Scopus and Web of Science were searched. The primary effectiveness outcome was ischaemic stroke. Safety outcomes were major bleeding, intracranial haemorrhage, gastrointestinal bleeding, myocardial infarction, and mortality. Twenty-two studies were eligible for inclusion. Two studies related specifically to people ≥75 years but were excluded from meta-analysis due to low quality; all data in the meta-analyses were from subgroups. The pooled risk estimate of ischaemic stroke was slightly lower for DOACs. There was no significant difference in major bleeding, mortality, or myocardial infarction. Risk of intracranial haemorrhage was 44% lower with DOACs, but risk of GI bleeding was 46% higher. Our results suggest that DOACs may be preferable for the majority of older patients with AF, provided they are not at significant risk of a GI bleed. However, these results are based entirely on data from subgroup analyses so should be interpreted cautiously. There is a need for adequately powered research in this patient group.

scholarly journals Adverse prognosis of incidentally detected ambulatory atrial fibrillation

2014 ◽  
Vol 112 (08) ◽  
pp. 276-286 ◽  
Author(s):  
Carlos Martinez ◽  
Anja Katholing ◽  
Saul Freedman
Keyword(s):  
Myocardial Infarction ◽  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Antithrombotic Therapy ◽  
Oral Anticoagulant ◽  
Incidence Rates ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Antiplatelet Treatment ◽  
Stroke Incidence

SummaryIt was the aim of this study to determine prognosis of incidentally detected ambulatory atrial fibrillation (IA-AF) and its response to antithrombotic therapy. We performed a cohort study of 5,555 patients with IA-AF (mean age 70.9 ± 10.1, 38.4% female) and 24,705 age- and gender-matched controls without AF followed three years using UK Clinical Practice Research Datalink. We measured incidence rates of stroke, all-cause mortality, myocardial infarction, major bleeding, and effect of antithrombotic therapy. Patients with IA-AF had mean CHA2DS2VASc score 2.5 ± 1.5, 73% with score ≥2. The stroke incidence rate (IR) was 19.4 (95% confidence interval 17.1 – 21.9)/1,000 person-years vs 8.4 (7.7 – 9.1) in controls (p<0.001), mortality 40.1 (36.8 – 43.6)/1,000 person-years vs 20.9 (19.8 – 22.0) in controls (p<0.001), and myocardial infarction 9.0 (7.5 – 10.8)/1,000 person-years vs 6.5 (5.9 – 7.2) in controls (p<0.001). IRs of all endpoints increased with age. Oral anticoagulant ± antiplatelet therapy received by 51.0% in year following IA-AF was associated with adjusted hazard ratio (HR) of 0.35 (0.17 – 0.71) for stroke, and 0.56 (0.36 – 0.85) for death compared to no therapy, while antiplatelet treatment was associated with a non-significant reduction of HR: 0.81 (0.51 – 1.29) for stroke, and 0.80 (0.55 – 1.15) for death, though both carried a similar small non-significant adjusted excess IR of major bleeding. In conclusion, asymptomatic AF detected incidentally is associated with a significant adverse effect on stroke and death, with reduction in both associated with oral anticoagulant but not antiplatelet treatment. This provides justification to assess cost-effectiveness of community screening to detect unknown AF.

scholarly journals The optimal drug adherence to maximize the efficacy and safety of non-vitamin K antagonist oral anticoagulant in real-world atrial fibrillation patients

EP Europace ◽  
2019 ◽  
Vol 22 (4) ◽  
pp. 547-557 ◽  
Author(s):  
Daehoon Kim ◽  
Pil-Sung Yang ◽  
Eunsun Jang ◽  
Hee Tae Yu ◽  
Tae-Hoon Kim ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Atrial Fibrillation ◽  
Ischaemic Stroke ◽  
Clinical Outcomes ◽  
Vitamin K ◽  
Major Bleeding ◽  
Oral Anticoagulant ◽  
Vitamin K Antagonist ◽  
Increased Risk ◽  
Optimal Drug

Abstract Aims To investigate the association between adherence to non-vitamin K antagonist oral anticoagulant (NOAC) and clinical outcomes and to determine the optimal cut-off level of NOAC adherence among patients with atrial fibrillation (AF). Methods and results Using the Korean National Health Insurance Service database, we identified 96 197 patients with non-valvular AF who initiated NOAC or warfarin in 2013–16. We compared clinical outcomes between adherent [proportion of days covered (PDC) ≥80%] vs. non-adherent (PDC &lt;80%) NOAC users, and further with warfarin users. We assessed the outcomes according to different levels of adherence. The proportion of adherent NOAC users was 64.0%. Compared with non-adherent NOAC users, adherent NOAC users were at lower risks of ischaemic stroke/systemic embolism (SE) [adjusted hazard ratio (aHR) 0.73, 95% confidence interval (CI) 0.69–0.79], and myocardial infarction (aHR 0.82, 95% CI 0.72–0.93), whereas there was no significant risk alteration for major bleeding (aHR 1.01, 95% CI 0.91–1.11). Compared with warfarin, non-adherent NOAC use failed to have better efficacy against ischaemic stroke/SE (aHR 0.99, 95% CI 0.93–1.05) and rather had increased risk of myocardial infarction (aHR 1.13, 95% CI 1.03–1.25). In NOAC users, the risks of adverse outcomes decreased according to gradual increase of adherence rates with the lowest risks in ≥90%, except for major bleeding in which there were no significant associations. Conclusions In an adherence level-dependent fashion, adherent use of NOAC showed better clinical outcomes without increasing bleeding risk. Maintaining ≥90% of adherence optimizes effectiveness of NOAC therapy without compromising its safety.

Sepsis associated new onset atrial fibrillation; risk factors and long term outcomes

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
V Moosavi ◽  
M Paymard ◽  
R Ebrahimi ◽  
T Harvey ◽  
N Parkes ◽  
...  
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Ischaemic Stroke ◽  
Major Bleeding ◽  
Rate Control ◽  
Statistical Significance ◽  
Significant Difference ◽  
All Cause Mortality ◽  
New Onset

Abstract Background Atrial fibrillation (AF) is commonly encountered in the setting of systemic inflammation or infection. The optimal management of AF in this cohort and their long-term AF-related clinical outcome are unknown. Purpose The aims of our study were to evaluate the traditional and non-traditional AF risk factors and long-term AF-related clinical outcomes in patients who were diagnosed with new onset AF in the setting of sepsis. Methods In this retrospective cohort study, we used the medical records to identify patients who were diagnosed with the new onset AF during hospitalization for sepsis at our centre between 2013 and 2017. The primary clinical outcomes included 24-month risk of ischaemic stroke, major bleeding (gastrointestinal or intracranial bleeding), the recurrence of AF and the all-cause mortality. The patients with known AF or those who died during the index admission were excluded from the analysis. Results 5598 patients were admitted to our hospital between 2013 and 2017 with sepsis. Of this cohort, 126 patients (mean age 69.7 years, 62.7% male) developed new onset AF during the index hospital admission (72.2% required ICU admission). 38 patients (30.1%) died during the initial hospitalisation while 88 patients (69.9%) were discharged from hospital (32% anticoagulated). 14 patients (16%) died within 24 months. Hypertension (59%), CKD (30%), diabetes (21%), and CCF (17%) were the most common risk factors. Mean CHA2DS2VASC score was 2.56±1.4 and mean HAS BLED score was 2.5±1.3. Mean CRP and WCC were 228±119 and 12.3±9.1 respectively. Comparing risk factors, only HASBLED score showed statistical significance on 24 months mortality (p=0.036, 95% CI 0.43–1.52). The composite incidence of all-cause mortality and ischaemic stroke was three times lower in anticoagulated patients compared with those who did not receive anticoagulation even though this did not reach statistical significance (7.1% v 21.6% respectively, p=0.07; RR=0.32; 95% CI=0.79–1.36). There was no statistically significant difference between the two groups for major bleeding events (3.5% v 3.3% respectively, p=0.68; RR=1.07; 95% CI=0.10–11.3). Rhythm and rate control therapies showed no significant difference on the composite outcome of all-cause mortality, ischaemic stroke and recurrence of AF (28.0% v 28.9%, p=0.92; RR=0.96, 95% CI=0.49–1.88), however, there was a trend towards less recurrence of AF in patients who received rate or rhythm control therapies (12% vs 18% respectively p=0.44; RR=0.67; 95% CI=0.24–1.85). Conclusions Our study suggests that anticoagulation therapy in patients with sepsis associated new onset AF may decrease composite of all-cause mortality and ischaemic stroke without increasing major bleeding risk. Rhythm and rate control strategies did not decrease all-cause mortality, ischaemic stroke or risk of recurrence of AF. These findings can provide benchmarks for design of randomized control trials. Funding Acknowledgement Type of funding source: None

Premature permanent discontinuation of apixaban or warfarin in patients with atrial fibrillation

Heart ◽  
2020 ◽  
pp. heartjnl-2020-317229 ◽  
Author(s):  
Anthony P Carnicelli ◽  
Sana M Al-Khatib ◽  
Denis Xavier ◽  
Frederik Dalgaard ◽  
Peter D Merrill ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Study Drug ◽  
Treatment Groups ◽  
Patient Request ◽  
Clinical Events ◽  
Significant Difference ◽  
Ischaemic Attack

AimsThe ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial randomised patients with atrial fibrillation at risk of stroke to apixaban or warfarin. We sought to describe patients from ARISTOTLE who prematurely permanently discontinued study drug.Methods/ResultsWe performed a posthoc analysis of patients from ARISTOTLE who prematurely permanently discontinued study drug during the study or follow-up period. Discontinuation rates and reasons for discontinuation were described. Death, thromboembolism (stroke, transient ischaemic attack, systemic embolism), myocardial infarction and major bleeding rates were stratified by ≤30 days or >30 days after discontinuation. A total of 4063/18 140 (22.4%) patients discontinued study drug at a median of 7.3 (2.2, 15.2) months after randomisation. Patients with discontinuation were more likely to be female and had a higher prevalence of cardiovascular disease, diabetes, renal impairment and anaemia. Premature permanent discontinuation was more common in those randomised to warfarin than apixaban (23.4% vs 21.4%; p=0.002). The most common reasons for discontinuation were patient request (46.1%) and adverse event (34.9%), with no significant difference between treatment groups. The cumulative incidence of clinical events ≤30 days after premature permanent discontinuation for all-cause death, thromboembolism, myocardial infarction, and major bleeding was 5.8%, 2.6%, 0.9%, and 3.0%, respectively. No significant difference was seen between treatment groups with respect to clinical outcomes after discontinuation.ConclusionPremature permanent discontinuation of study drug in ARISTOTLE was common, less frequent in patients receiving apixaban than warfarin and was followed by high 30-day rates of death, thromboembolism and major bleeding. Initiatives are needed to reduce discontinuation of oral anticoagulation.

scholarly journals DOAC versus warfarin in patients with atrial fibrillation and stage IV-V chronic kideny disease including patients on dialysis

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
A Wartanian ◽  
C Lewinter ◽  
R Edfors
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Stage Iv ◽  
Intracranial Bleeding ◽  
Phase Iii ◽  
Gi Bleeding ◽  
Dialysis Patients ◽  
Systemic Embolism ◽  
All Cause Mortality

Abstract Introduction Patients with atrial fibrillation (AF) and severe chronic kidney disease (CKD) were excluded from most phase III randomized controlled trials (RCTs) of direct oral anticoagulants (DOACs). Evidence of warfarin versus DOAC in the AF population with stage IV-V CKD is therefore limited. Aim To evaluate the effectiveness and safety of DOAC compared with warfarin on this population including dialysis patients. Methods A systematic review and meta-analysis of RCTs and observational studies involving AF patients with stage IV-V CKD treated with warfarin versus DOACs were conducted to evaluate the following outcomes: stroke (ischemic and hemorrhagic) or systemic embolism (SE), all-cause mortality, major bleeding, gastrointestinal (GI) bleeding, and intracranial bleeding. If the heterogeneity between studies was moderate to high calculated as the I2 ≥50%, a meta regression was undertaken between baseline characteristics and the study outcomes. We conducted a literature search using key words related to AF, severe CKD, DOAC and warfarin in PubMed, Embase and Cochrane Library. Results Nine studies were included in the meta-analysis. Compared to warfarin, DOAC was significantly associated with a reduced risk of stroke or systemic embolism (SE) (risk ratio [RR] = 0.69; 95% confidence interval [CI] 0.50–0.95) (Figure 1), intracranial bleeding (RR=0.54; 95% CI 0.35–0.84) and hemorrhagic stroke (RR=0.39; 95% CI 0.16–0.95). There was no significant difference between DOACs and warfarin in the risk of all-cause mortality (RR=0.80; 95% CI 0.57–1.13), major bleeding (RR = 0.70; 95% CI 0.44–1.11) (Figure 2) and GI bleeding (RR=0.76; 95% CI 0.56–1.02). For the outcome stroke or SE, dabigatran (compared with apixaban) significantly eliminated the net effect of DOAC as compared with warfarin (coefficient, 0.8; P=0.003). Regarding major bleeding, rivaroxaban and dabigatran both eliminated the DOAC effect from the meta-analysis as compared to apixaban (P=0.01 & P&lt;0.0001). Dabigatran significantly increased the risk of GI bleeding in comparison to apixaban (coefficient, 0.48; P=0.002) in comparison with the overall similar effect of warfarin in the meta-analysis. Conclusion Among patients with AF and stage IV or V CKD including dialysis patients, DOAC appears to have similar or better effectiveness and safety compared to warfarin. FUNDunding Acknowledgement Type of funding sources: None. Stroke or systemic embolism

Abstract 20218: Comparative Effectiveness of Dabigatran and Rivaroxaban versus Warfarin in Patients With Non-Valvular Atrial Fibrillation

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Lindsay Bengtson ◽  
Lin Chen ◽  
Richard MacLehose ◽  
Pamela Lutsey ◽  
Alvaro Alonso
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Real World ◽  
Proportional Hazards ◽  
Oral Anticoagulants ◽  
Cox Proportional Hazards ◽  
Intracranial Bleeding ◽  
Gi Bleeding ◽  
Pharmacy Claims ◽  
The Us

Background: In randomized trials, the new oral anticoagulants (NOAC) dabigatran and rivaroxaban have been at least as efficacious as warfarin in the prevention of ischemic stroke in patients with non-valvular atrial fibrillation (NVAF). Information on the effectiveness of NOACs versus warfarin in real-world populations in the US is more limited. Methods: We used data from the US MarketScan Commercial and Medicare Supplemental databases in the period 2010-12. We selected patients initiating oral anticoagulants after NVAF diagnosis, and with at least 6 months of enrollment before first anticoagulant use. Patients initiating dabigatran or rivaroxaban were matched with up to 5 warfarin users by age, sex, and time in the database. Outcomes of interest (ischemic stroke, intracranial bleeding, and gastrointestinal [GI] bleeding) were defined according to validated algorithms. Information on other comorbidities and medication use was obtained from inpatient, outpatient, and pharmacy claims. High-dimensional propensity score-adjusted Cox proportional hazards regression was used to estimate the association of NOACs vs warfarin with each outcome of interest. Results: The analysis included 32,918 dabigatran, 3,301 rivaroxaban and 92,633 warfarin users with NVAF. During an average 13-month follow-up (6 for rivaroxaban, 15 for dabigatran), 1035 ischemic strokes, 225 intracranial bleeds, and 1842 GI bleeds were identified. Rate of ischemic stroke was similar in patients initiating NOACs compared to those on warfarin. However, rate of intracranial bleeding was lower in patients using NOACs compared to warfarin users, while GI bleeding rate was higher in dabigatran users than warfarin users (Table). Conclusion: In this large real-world patient population, effectiveness of NOACs (compared to warfarin) for diverse outcomes was comparable to efficacy reported in the RE-LY and ROCKET-AF trials.

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

2016 ◽  
Vol 116 (11) ◽  
pp. 975-986 ◽  
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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