Major bleeding risk assessment in atrial fibrillation patients taking vitamin K antagonists

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.

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Bleeding and related mortality with NOACs and VKAs in newly diagnosed atrial fibrillation: results from the GARFIELD-AF registry

Blood Advances ◽

10.1182/bloodadvances.2020003560 ◽

2021 ◽

Vol 5 (4) ◽

pp. 1081-1091

Author(s):

Jean-Pierre Bassand ◽

Saverio Virdone ◽

Marc Badoz ◽

Freek W. A. Verheugt ◽

A. John Camm ◽

...

Keyword(s):

Atrial Fibrillation ◽

Vitamin K ◽

Major Bleeding ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Bleeding Risk ◽

Minor Bleeding ◽

Newly Diagnosed ◽

Risk Of Death ◽

Major Bleed

Abstract In atrial fibrillation (AF), lower risks of death and bleeding with non-vitamin-K oral anticoagulants (NOACs) were reported in meta-analyses of controlled trials, but whether these findings hold true in real-world practice remains uncertain. Risks of bleeding and death were assessed in 52 032 patients with newly diagnosed AF enrolled in GARFIELD-AF (Global Anticoagulant Registry in the FIELD–Atrial Fibrillation), a worldwide prospective registry. Baseline treatment was vitamin K antagonists (VKAs) with or without antiplatelet (AP) agents (VKA ± AP) (20 151; 39.3%), NOACs ± AP agents (14 103; 27.5%), AP agents only (10 748; 21.0%), or no antithrombotics (6219; 12.1%). One-year follow-up event rates (95% confidence interval [CI]) of minor, clinically relevant nonmajor (CRNM), and major bleedings were 2.29 (2.16-2.43), 1.10 (1.01-1.20), and 1.31 (1.21-1.41) per 100 patient-years, respectively. Bleeding risk was lower with NOACs than VKAs for any bleeding (hazard ratio (HR) [95% CI]), 0.85 [0.73-0.98]) or major bleeding (0.79 [0.60-1.04]). Compared with no bleeding, the risk of death was higher with minor bleeding (adjusted HR [aHR], 1.53 [1.07-2.19]), CRNM bleeding (aHR, 2.59 [1.80-3.73]), and major bleeding (aHR, 8.24 [6.76-10.04]). The all-cause mortality rate was lower with NOACs than with VKAs (aHR, 0.73 [0.62-0.85]). Forty-five percent (114) of all deaths occurred within 30 days, and 40% of these were from intracranial/intraspinal hemorrhage (ICH). The rates of any bleeding and all-cause death were lower with NOACs than with VKAs. Major bleeding was associated with the highest risk of death. CRNM bleeding and minor bleeding were associated with a higher risk of death compared to no bleeding. Death within 30 days after a major bleed was most frequently related to ICH. This trial was registered at www.clinicaltrials.gov as #NCT01090362.

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Comparison of Left Atrial Appendage Occlusion versus Non-Vitamin-K Antagonist Oral Anticoagulation in High-Risk Atrial Fibrillation: An Update

Journal of Cardiovascular Development and Disease ◽

10.3390/jcdd8060069 ◽

2021 ◽

Vol 8 (6) ◽

pp. 69

Author(s):

Shaojie Chen ◽

K. R. Julian Chun ◽

Zhiyu Ling ◽

Shaowen Liu ◽

Lin Zhu ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

High Risk ◽

Vitamin K ◽

Major Bleeding ◽

Left Atrial ◽

Left Atrial Appendage ◽

Vitamin K Antagonists ◽

Left Atrial Appendage Occlusion ◽

The Mean

Transcatheter left atrial appendage occlusion (LAAO) is non-inferior to vitamin K antagonists (VKAs) in preventing thromboembolic events in atrial fibrillation (AF). Non-vitamin K antagonists (NOACs) have an improved safety profile over VKAs; however, evidence regarding their effect on cardiovascular and neurological outcomes relative to LAAO is limited. Up-to-date randomized trials or propensity-score-matched data comparing LAAO vs. NOACs in high-risk patients with AF were pooled in our study. A total of 2849 AF patients (LAAO: 1368, NOACs: 1481, mean age: 75 ± 7.5 yrs, 63.5% male) were enrolled. The mean CHA2DS2-VASc score was 4.3 ± 1.7, and the mean HAS-BLED score was 3.4 ± 1.2. The baseline characteristics were comparable between the two groups. In the LAAO group, the success rate of device implantation was 98.8%. During a mean follow-up of 2 years, as compared with NOACs, LAAO was associated with a significant reduction of ISTH major bleeding (p = 0.0002). There were no significant differences in terms of ischemic stroke (p = 0.61), ischemic stroke/thromboembolism (p = 0.63), ISTH major and clinically relevant minor bleeding (p = 0.73), cardiovascular death (p = 0.63), and all-cause mortality (p = 0.71). There was a trend toward reduction of combined major cardiovascular and neurological endpoints in the LAAO group (OR: 0.84, 95% CI: 0.64–1.11, p = 0.12). In conclusion, for high-risk AF patients, LAAO is associated with a significant reduction of ISTH major bleeding without increased ischemic events, as compared to “contemporary NOACs”. The present data show the superior role of LAAO over NOACs among high-risk AF patients in terms of reduction of major bleeding; however, more randomized controlled trials are warranted.

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GW28-e0461 Durations of Anticoagulation and Major Bleeding Risk of Vitamin K Antagonists for Venous Thromboembolism: A Meta-Analysis

Journal of the American College of Cardiology ◽

10.1016/j.jacc.2017.07.295 ◽

2017 ◽

Vol 70 (16) ◽

pp. C84

Author(s):

Wei Wang ◽

Chunyan Wu ◽

Han Yu ◽

Yang Yang ◽

Jue Li

Keyword(s):

Venous Thromboembolism ◽

Vitamin K ◽

Major Bleeding ◽

Meta Analysis ◽

Vitamin K Antagonists ◽

Bleeding Risk

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Non-vitamin K antagonist oral anticoagulants vs. vitamin-K antagonists in patients with atrial fibrillation and chronic kidney disease: a nationwide cohort study

Thrombosis Journal ◽

10.1186/s12959-019-0211-y ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 2

Author(s):

Emma Kirstine Laugesen ◽

Laila Staerk ◽

Nicholas Carlson ◽

Anne-Lise Kamper ◽

Jonas Bjerring Olesen ◽

...

Keyword(s):

Atrial Fibrillation ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Vitamin K ◽

Major Bleeding ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Vitamin K Antagonist ◽

All Cause Mortality ◽

Comparable Population

Abstract Background We aimed to compare effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) versus vitamin-K antagonists (VKA) in atrial fibrillation (AF) patients with chronic kidney disease (CKD) not receiving dialysis. Methods By using personal identification numbers, we cross-linked individual-level data from Danish administrative registries. We identified every citizen with a prior diagnosis of AF and CKD who initiated NOAC or VKA (2011–2017). An external analysis of 727 AF patients with CKD (no dialysis) was performed to demonstrate level of kidney function in a comparable population. Study outcomes included incidents of stroke/thromboembolisms (TEs), major bleedings, myocardial infarctions (MIs), and all-cause mortality. We used Cox proportional hazards models to determine associations between oral anticoagulant treatment and outcomes. Results Of 1560 patients included, 1008 (64.6%) initiated VKA and 552 (35.4%) initiated NOAC. In a comparable population we found that 95.3% of the patients had an estimated glomerular filtration rate (eGFR) < 59 mL/min. Patients treated with NOAC had a significantly decreased risk of major bleeding (hazard ratio (HR): 0.47, 95% confidence interval (CI): 0.26–0.84) compared to VKA. There was not found a significant association between type of anticoagulant and risk of stroke/TE (HR: 0.83, 95% CI: 0.39–1.78), MI (HR: 0.45, 95% CI: 0.18–1.11), or all-cause mortality (HR: 0.99, 95% CI: 0.77–1.26). Conclusion NOAC was associated with a lower risk of major bleeding in patients with AF and CKD compared to VKA. No difference was found in risk of stroke/TE, MI, and all-cause mortality.

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Direct oral anticoagulants versus vitamin K antagonists in patients with atrial fibrillation and cancer a meta-analysis

Journal of Thrombosis and Thrombolysis ◽

10.1007/s11239-020-02304-3 ◽

2020 ◽

Cited By ~ 2

Author(s):

Marco Valerio Mariani ◽

Michele Magnocavallo ◽

Martina Straito ◽

Agostino Piro ◽

Paolo Severino ◽

...

Keyword(s):

Atrial Fibrillation ◽

Vitamin K ◽

Major Bleeding ◽

Meta Analysis ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Significant Risk ◽

Bleeding Complications ◽

Efficacy And Safety

Abstract Background Direct oral anticoagulants (DOACs) are recommended as first-line anticoagulants in patients with atrial fibrillation (AF). However, in patients with cancer and AF the efficacy and safety of DOACs are not well established. Objective We performed a meta-analysis comparing available data regarding the efficacy and safety of DOACs vs vitamin K antagonists (VKAs) in cancer patients with non-valvular AF. Methods An online search of Pubmed and EMBASE libraries (from inception to May, 1 2020) was performed, in addition to manual screening. Nine studies were considered eligible for the meta-analysis involving 46,424 DOACs users and 182,797 VKA users. Results The use of DOACs was associated with reduced risks of systemic embolism or any stroke (RR 0.65; 95% CI 0.52–0.81; p 0.001), ischemic stroke (RR 0.84; 95% CI 0.74–0.95; p 0.007) and hemorrhagic stroke (RR 0.61; 95% CI 0.52–0.71; p 0.00001) as compared to VKA group. DOAC use was associated with significantly reduced risks of major bleeding (RR 0.68; 95% CI 0.50–0.92; p 0.01) and intracranial or gastrointestinal bleeding (RR 0.64; 95% CI 0.47–0.88; p 0.006). Compared to VKA, DOACs provided a non-statistically significant risk reduction of the outcomes major bleeding or non-major clinically relevant bleeding (RR 0.94; 95% CI 0.78–1.13; p 0.50) and any bleeding (RR 0.91; 95% CI 0.78–1.06; p 0.24). Conclusions In comparison to VKA, DOACs were associated with a significant reduction of the rates of thromboembolic events and major bleeding complications in patients with AF and cancer. Further studies are needed to confirm our results.

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4037Nurse counseling of patients with atrial fibrillation to improve compliance to oral anticoagulation

European Heart Journal ◽

10.1093/eurheartj/ehz745.0092 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

R Chilian-Hof ◽

S Schnupp ◽

C Mahnkopf ◽

J Brachmann ◽

C Kleinecke

Keyword(s):

Atrial Fibrillation ◽

Vitamin K ◽

Oral Anticoagulation ◽

Vitamin K Antagonists ◽

Randomised Trial ◽

Female Gender ◽

Bleeding Risk ◽

Telephone Counseling ◽

Bleeding Events

Abstract Background Atrial fibrillation (AF) is the most frequent arrhythmia with a prevalence of 1%–2% in the general population. Oral anticoagulation (OAC) is state-of-the art for preventions of thromboembolic events, in particular ischemic stroke, in patients with atrial fibrillation. Despite its proven benefit, numerous studies have documented under use of OAC for a variety of reasons. Purpose To establish a program of nurse counseling in patient with atrial fibrillation and treatment with oral anticoagulation. The program is designed to improve patients satisfaction, compliance to OAC, prevention of medication errors, ischemic and bleeding events. Methods Patients with atrial fibrillation and treatment with oral anticoagulation were prospectively identified at the department of cardiology of our clinic. They received a 30 minutes nurse counseling about oral anticoagulation during the hospital stay and another 30 minutes telephone counseling 3 months after inclusion. Furthermore, they received a brochure to inform about atrial fibrillation, oral anticoagulation and methods to improve medication compliance. Demographic characteristics with stroke and bleeding risk (CHA2DS2-VASc and HAS-BLED scores), as well as procedural data were systematically assessed in a predefined standardized way and captured in a dedicated database. Results Between June 2017 and January 2018, a total of 617 patients (female gender: 43.1%) with atrial fibrillation and oral anticoagulation received nurse counseling. Demographic and follow-up data of 204 patients (female gender: 85/204 (41.7%); mean age 69.7±17.3, CHA2DS2-VASc score 4.2±1.7, HAS-BLED score 2.8±0.37) were assessed in a dedicated database. Indication for OAC was paroxysmal and persistent/permanent AF in 110/204 (53.9%), 93/204 (45.6%) and others 17 (8.3%), respectively. 33/2014 (16.2%) were treated with vitamin K antagonists, and 172/204 (84.3%) with non-vitamin K antagonists. After a follow-up of 0.46±2.9 years and 187 patients-years the rates of cardiovascular death, major bleeding events and all-cause stroke and TIA were 1.07%, 2.14% and 1.61% per 100 patient-years. Conclusion Nurse counseling in patients with atrial fibrillation and treatment with oral anticoagulation has been established at the REGIOMED clinics, Germany. Its effectiveness in terms of quality of live, medication complications and cardiovascular events has to be proven in a randomised trial. Acknowledgement/Funding Daichi-Sankyo

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P690Incidence of events between vitamin K antagonists and direct oral anticoagulants in patients with cancer

European Heart Journal ◽

10.1093/eurheartj/ehz747.0295 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

A Pardo Sanz ◽

L M Rincon ◽

G De Lara ◽

A Tamayo ◽

L C Belarte ◽

...

Keyword(s):

Breast Cancer ◽

Vitamin K ◽

Major Bleeding ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Bleeding Risk ◽

Systemic Embolism ◽

Bleeding Events ◽

Patients With Cancer

Abstract Background Balance between embolic and bleeding risk is challenging in patients with cancer. There is a lack of specific recommendations for the use of antithrombotic therapy in oncologic patients with atrial fibrillation (AF). We aimed to evaluate the effectiveness and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) within patients with breast cancer. We also compared the embolic and bleeding risk, the preventive management and the incidence of events between patients with and without cancer. Methods It is an ambispective observational multicentric study that analysed patients with non-valvular AF treated in Oncology and Cardiology Departments in Spain in the period 2011–2018. A total of 1237 female patients with AF were enrolled: 637 with breast cancer and 599 without cancer. The incidence of thromboembolic and major bleeding events according to the antithrombotic strategy with VKAs or DOACs was evaluated in the cohort of 637 patients with cancer. Analysis were conducted using SPSS software V.22.0 and R V.3.5.1, with a two-tailed significance value of 0.05. Results Mean follow-up was 3.1 years. Both groups were similar in age, CHA2DS2-VASc and HASB-LED scores. There was no evidence that the incidence of ischemic stroke/systemic embolism differed between patients with cancer treated with AVK and DOAC after CHA2DS2-VASc adjustment: HR 0.91 (95% CI, 0.42–1.99). In addition, no significant differences in the incidence of major bleeding events were found between DOACs and VKA after adjustment for HAS-BLED score: HR 1.53 (95% CI, 0.93–2.53) (Figure 3). Gastrointestinal bleeding was the main source of haemorrhages in both groups (45% of bleedings among patients treated with DOACs and, 37% in VKAs group). Metastatic disease or active chemotherapy were studied as potential covariates but none of them posed any relevant change in the result. Kaplan-Meier analysis Conclusions Cancer patients treated with DOACs did not differ versus those treated with VKAs with regards to stroke or systemic embolism in a model adjusted for CHA2DS2-VASc. Neither significant differences were found for bleeding events in a model adjusted for baseline HASBLED.

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Bleeding risk with rivaroxaban compared with vitamin K antagonists in patients aged 80 years or older with atrial fibrillation

Heart ◽

10.1136/heartjnl-2020-317923 ◽

2020 ◽

pp. heartjnl-2020-317923 ◽

Cited By ~ 1

Author(s):

Olivier Hanon ◽

Jean-Sébastien Vidal ◽

George Pisica-Donose ◽

Galdric Orvoën ◽

Jean-Philippe David ◽

...

Keyword(s):

Atrial Fibrillation ◽

Propensity Score ◽

Vitamin K ◽

Lower Risk ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Bleeding Risk ◽

Matched Sample ◽

Intracerebral Bleeding

ObjectiveDirect oral anticoagulants have been evaluated in the general population, but proper evidence for their safe use in the geriatric population is still missing. We compared the bleeding risk of a direct oral anticoagulant (rivaroxaban) and vitamin K antagonists (VKAs) among French geriatric patients with non-valvular atrial fibrillation (AF) aged ≥80 years.MethodsWe performed a sequential observational prospective cohort study, using data from 33 geriatric centres. The sample comprised 908 patients newly initiated on VKAs between September 2011 and September 2014 and 995 patients newly initiated on rivaroxaban between September 2014 and September 2017. Patients were followed up for up to 12 months. One-year risks of major, intracerebral, gastrointestinal bleedings, ischaemic stroke and all-cause mortality were compared between rivaroxaban-treated and VKA-treated patients with propensity score matching and Cox models.ResultsMajor bleeding risk was significantly lower in rivaroxaban-treated patients (7.4/100 patient-years) compared with VKA-treated patients (14.6/100 patient-years) after multivariate adjustment (HR 0.66; 95% CI 0.43 to 0.99) and in the propensity score–matched sample (HR 0.53; 95% CI 0.33 to 0.85). Intracerebral bleeding occurred less frequently in rivaroxaban-treated patients (1.3/100 patient-years) than in VKA-treated patients (4.0/100 patient-years), adjusted HR 0.59 (95% CI 0.24 to 1.44) and in the propensity score–matched sample HR 0.26 (95% CI 0.09 to 0.80). Major lower bleeding risk was largely driven by lower risk of intracerebral bleeding.ConclusionsOur study findings indicate that bleeding risk, largely driven by lower risk of intracerebral bleeding, is lower with rivaroxaban than with VKA in stroke prevention in patients ≥80 years old with non-valvular AF.

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Antikoagulation bei Vorhofflimmern

Hämostaseologie ◽

10.5482/ha-1186 ◽

2012 ◽

Vol 32 (01) ◽

pp. 37-39 ◽

Cited By ~ 5

Author(s):

C. Bode ◽

M. Moser

Keyword(s):

Atrial Fibrillation ◽

Vitamin K ◽

Vitamin K Antagonists ◽

Bleeding Risk ◽

Coagulation Factors ◽

Additional Risk ◽

New Anticoagulants ◽

Therapeutic Anticoagulation ◽

Impaired Quality

SummaryAtrial fibrillation is one of the most frequent reasons for therapeutic anticoagulation in everyday practice. Oral vitamin K antagonists such as Marcumar have been state of the art anticoagulants to prevent thrombembolic events in patients with atrial fibrillation and additional risk factors. But these drugs are accompanied by disadvantages such as increased bleeding risk and impaired quality of life caused by interactions with food or other medications as well as frequent controls of INRs.The new anticoagulants apixaban, rivaroxaban and dabigatran are direct antagonists of coagulation factors (FXa or FIIa) and demonstrate a promising risk/benefit profile in large clinical trials compared with vitamin K antagonists.Their approval for clinical use will open up new therapeutic perspectives for patients with atrial fibrillation and indication for anticoagulation.

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