New score for assessing bleeding risk in patients with atrial fibrillation treated with NOACs

BackgroundInformation is needed on bleeding risk factors specific for patients with atrial fibrillation (AF) treated with non-vitamin K oral anticoagulants (NOACs). We aimed to identify risk factors in a large real-world cohort and to derive a bleeding risk score for patients with AF treated with NOACs.MethodsFrom nationwide registries (the Norwegian Patient Registry and the Norwegian Prescription Database), we identified patients with AF with a first prescription of a NOAC between January 2013 and June 2015. Cox proportional-hazards analysis was used to identify the strongest risk factors for major or clinically relevant non-major (CRNM) bleeding. Based on these, a risk prediction score was derived. Discrimination was assessed with Harrel’s C-index. C-indexes for the modified Hypertension, Age, Stroke, Bleeding tendency/predisposition, Labile international normalised ratios, Elderly age, Drugs or alcohol excess (HAS-BLED), the Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) and the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT) scores were also calculated from the same cohort.ResultsAmong 21 248 NOAC-treated patients with a median follow-up time of 183 days, 1257 (5.9%) patients experienced a major or CRNM bleeding. Ten independent risk factors for bleeding were identified, which when included in a risk prediction model achieved a C-index of 0.68 (95% CI 0.66 to 0.70). A simplified score comprising three variables; age, history of bleeding and non-bleeding related hospitalisation within the last 12 months, yielded a c-index of 0.66 (95% CI 0.65 to 0.68). In the same cohort, the modified HAS-BLED, ATRIA and ORBIT scores achieved c-indexes of 0.62 (95% CI 0.60 to 0.63), 0.66 (95% CI 0.64 to 0.67) and 0.66 (95% CI 0.64 to 0.67), respectively.ConclusionsOur proposed simplified bleeding score could be a useful clinical tool for quick estimation of risk of bleeding in patients with AF treated with NOACs.

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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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Regarding the management of an elderly patient with atrial fibrillation

Medicine of Ukraine ◽

10.37987/1997-9894.2021.8(254).245797 ◽

2021 ◽

pp. 20-26

Author(s):

O. M. Bilovol ◽

I. I. Knyazkova

Keyword(s):

Risk Factors ◽

Atrial Fibrillation ◽

Health Professionals ◽

Oral Anticoagulants ◽

Bleeding Risk ◽

Critical Conditions ◽

Pharmacological Effects ◽

Thromboembolic Complications ◽

Risk Of Bleeding ◽

Age Related

The increase in the proportion of elderly people observed in the population is accompanied by an increase in the prevalence of age-related diseases, including atrial fibrillation. In the treatment of such patients it is necessary to discuss the feasibility of prescribing anticoagulants to prevent ischemic stroke and systemic thromboembolism. The article presents scales that are used to assess the risk of thromboembolic complications and the risk of bleeding. The parameters that should be taken into account when prescribing oral anticoagulants to elderly patients are determined, the principles of bleeding risk management are given. The listed risk factors for bleeding, which are modified, potentially modified and not modified. Attention is paid to the description of specific antidotes to oral anticoagulants, the use of which has expanded in recent years, so many health professionals should know the main pharmacological effects of these drugs, be able to assess their anticoagulant effect in critical conditions and optimally cancel if necessary.

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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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Atrial fibrillation in the elderly

ESC CardioMed ◽

10.1093/med/9780198784906.003.0522 ◽

2018 ◽

pp. 2221-2223

Author(s):

David Hirsh ◽

Nanette Wenger

Keyword(s):

Atrial Fibrillation ◽

Heart Rate ◽

Elderly Patients ◽

Systolic Function ◽

Beta Blockers ◽

Oral Anticoagulants ◽

Left Ventricular Systolic Function ◽

Bleeding Risk ◽

Channel Blockers ◽

Elderly Age

The prevalence of atrial fibrillation (AF) increases with age, with about one-third of patients with AF older than 80 years. Rate control is the preferable strategy using beta blockers or, if left ventricular systolic function is intact, non-dihydropyridine calcium channel blockers. A more lenient heart rate target (<110 bpm resting heart rate) may require fewer agents and obviate the need for cardiac pacing secondary to bradycardia. Although palpitations and heart failure are the most common presentations, some elderly patients may have minimal symptoms. Anticoagulation is the treatment of choice for patients with a CHA2DS2-VASC score greater than 2; since age over 75 years is assigned 2 points, most such patients should be anticoagulated. Of concern in ascertaining the risk:benefit ratio of anticoagulation is that the study cohorts in AF anticoagulant trials are younger than community AF patients. This chapter includes a table listing the dose reductions required for the newer direct acting oral anticoagulants (dabigatran, rivaroxaban, and apixaban). In general, clinical practitioners overestimate the fall risk in their elderly patients, denying them the benefit of anticoagulation. The HAS-BLED and HEMOR2HAGES scores can aid in determining bleeding risk at elderly age.

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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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Incident Risk Factors and Major Bleeding in Patients with Atrial Fibrillation Treated with Oral Anticoagulants: A Comparison of Baseline, Follow-up and Delta HAS-BLED Scores with an Approach Focused on Modifiable Bleeding Risk Factors

Thrombosis and Haemostasis ◽

10.1055/s-0038-1636534 ◽

2018 ◽

Vol 47 (04) ◽

pp. 768-777 ◽

Cited By ~ 51

Author(s):

Tze-Fan Chao ◽

Yenn-Jiang Lin ◽

Shih-Lin Chang ◽

Li-Wei Lo ◽

Yu-Feng Hu ◽

...

Keyword(s):

Risk Factors ◽

Atrial Fibrillation ◽

Major Bleeding ◽

Oral Anticoagulants ◽

Bleeding Risk ◽

Modifiable Risk Factors ◽

The Mean ◽

Regular Review

Aim When assessing bleeding risk in patients with atrial fibrillation (AF), risk stratification is often based on the baseline risks. We aimed to investigate changes in bleeding risk factors and alterations in the HAS-BLED score in AF patients. We hypothesized that a follow-up HAS-BLED score and the ‘delta HAS-BLED score’ (reflecting the change in score between baseline and follow-up) would be more predictive of major bleeding, when compared with baseline HAS-BLED score. Methods and Results A total of 19,566 AF patients receiving warfarin and baseline HAS-BLED score ≤2 were studied. After a follow-up of 93,783 person-years, 3,032 major bleeds were observed. The accuracies of baseline, follow-up, and delta HAS-BLED scores as well as cumulative numbers of baseline modifiable bleeding risk factors, in predicting subsequent major bleeding, were analysed and compared. The mean baseline HAS-BLED score was 1.43 which increased to 2.45 with a mean ‘delta HAS-BLED score’ of 1.03. The HAS-BLED score remained unchanged in 38.2% of patients. Of those patients experiencing major bleeding, 76.6% had a ‘delta HAS-BLED’ score ≥1, compared with only 59.0% in patients without major bleeding (p < 0.001). For prediction of major bleeding, AUC was significantly higher for the follow-up HAS-BLED (0.63) or delta HAS-BLED (0.62) scores, compared with baseline HAS-BLED score (0.54). The number of baseline modifiable risk factors was non-significantly predictive of major bleeding (AUC = 0.49). Conclusion In this ‘real-world’ nationwide AF cohort, follow-up HAS-BLED or ‘delta HAS-BLED score’ was more predictive of major bleeding compared with baseline HAS-BLED or the simple determination of ‘modifiable bleeding risk factors’. Bleeding risk in AF is a dynamic process and use of the HAS-BLED score should be to ‘flag up’ patients potentially at risk for more regular review and follow-up, and to address the modifiable bleeding risk factors during follow-up visits.

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Major bleeding and intracranial hemorrhage risk prediction in patients with atrial fibrillation: Attention to modifiable bleeding risk factors or use of a bleeding risk stratification score? A nationwide cohort study

International Journal of Cardiology ◽

10.1016/j.ijcard.2017.11.025 ◽

2018 ◽

Vol 254 ◽

pp. 157-161 ◽

Cited By ~ 30

Author(s):

Tze-Fan Chao ◽

Gregory Y.H. Lip ◽

Yenn-Jiang Lin ◽

Shih-Lin Chang ◽

Li-Wei Lo ◽

...

Keyword(s):

Risk Factors ◽

Atrial Fibrillation ◽

Cohort Study ◽

Risk Stratification ◽

Risk Prediction ◽

Intracranial Hemorrhage ◽

Major Bleeding ◽

Bleeding Risk ◽

Hemorrhage Risk ◽

Risk Stratification Score

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Bleeding risk in anticoagulated patients with atrial fibrillation

ESC CardioMed ◽

10.1093/med/9780198784906.003.0515 ◽

2018 ◽

pp. 2195-2198

Author(s):

Margaret C. Fang

Keyword(s):

Risk Factors ◽

Atrial Fibrillation ◽

Intracranial Haemorrhage ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Bleeding Risk ◽

Clinical Risk Factors ◽

Anticoagulation Management ◽

Clinical Risk

Bleeding is the primary complication associated with chronic anticoagulant treatment of atrial fibrillation and can range from minor, clinically insignificant bleeds to life-threatening events. Anticoagulants increase an individual’s bleeding risk by approximately 2–2.5-fold. The absolute rates of bleeding vary depending on the presence or absence of specific clinical risk factors, as well as the type of anticoagulant and the quality of anticoagulation management. There are many clinical risk factors for bleeding including older age, hypertension, prior bleeding, anaemia, and kidney impairment. Concomitant use of other medications, in particular other antithrombotic/antiplatelet drugs, also significantly raises bleeding risk. Intracranial haemorrhage, a relatively uncommon but widely feared complication of anticoagulants, results in a 30-day mortality of about 40%. Risk factors for intracranial haemorrhage include advanced age, elevated blood pressure, a history of cerebrovascular disease, and cerebral amyloid angiopathy. A number of risk stratification schemes have been developed in order to better estimate the risk of anticoagulant-related bleeding. Most of the risk schemes were developed and validated in patients taking vitamin K antagonists, but have increasingly been applied to populations taking the newer direct oral anticoagulants. Although bleeding risk tools can be useful to assist in counselling patients about their bleeding risk, in general, these risk schemes are only moderately predictive and are probably best applied to patients who are considered reasonable candidates for anticoagulation and who are on the lower end of ischaemic stroke risk.

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