scholarly journals Comparative effectiveness of NOAC vs VKA in patients representing common clinical challenges: results from the GARFIELD-AF registry

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
S Virdone ◽  
J.C.L Himmelreich ◽  
K.S Pieper ◽  
A.J Camm ◽  
J.-P Bassand ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Renal Impairment ◽  
Elderly Patients ◽  
Vitamin K ◽  
Comparative Effectiveness ◽  
Bleeding Risk ◽  
Phase Iii ◽  
Considerable Proportion ◽  
The Impact ◽  
Anticoagulated Patients

Abstract Introduction Large phase III trials of non-valvular atrial fibrillation (AF) patients have shown a favourable risk-to-benefit ratio with Non-Vitamin K antagonist oral anticoagulants (NOAC) compared to Vitamin K antagonists (VKA). Although the results of these trials are directly applicable to many AF patients, important subsets of patients were under-represented. Thus, there remains uncertainty about the safety and effectiveness of NOAC therapy in common challenging scenarios. Purpose The main purpose of this study is to quantify and compare the impact of NOAC vs VKA in settings where clinical uncertainty still exists and represents a considerable proportion of AF patients in clinical practice. Methods The analysis was conducted in patients enrolled in the largest AF multinational prospective registry (the Global Anticoagulant Registry in the FIELD–Atrial Fibrillation, GARFIELD-AF). We evaluated the effectiveness and safety of NOAC compared to VKA in three groups of patients representing common clinical challenges (CCC): 1) elderly patients (i.e. age ≥75), 2) increased bleeding risk (i.e. HAS-BLED ≥3 or prior bleeding), and 3) renal impairment (i.e. CKD stages II to IV). We applied a propensity score using an overlap weighting scheme to obtain unbiased estimates of the treatment effect within each CCC group. Weights were applied to Cox proportional hazards models to estimate the effects of the NOAC vs VKA comparison on the occurrence of death, non-haemorrhagic stroke/SE and major bleeding within 2 years of enrolment. Results Comparative effectiveness of NOAC vs VKA was assessed in 8607 elderly patients, 1711 with increased bleeding risk, and 4460 with renal impairment. The proportion of anticoagulated patients was low in patients with increased bleeding risk (59%), while in the other two CCC groups the corresponding proportion was close to the one in the overall population (72%). Among anticoagulated patients, NOAC were prescribed to 50–55% of patients in the CCC groups. Patients with a high risk of bleeding and impaired kidney function were less likely to be prescribed NOAC instead of VKA compared with the overall anticoagulated population (−5.4% and −4.7%, respectively). Propensity-weighted hazard ratios for all-cause mortality favored NOAC (vs VKA) in all three CCC groups: 0.86 (95% CI: 0.74–0.99) for elderly patients, 0.73 (0.53–1.00) for patients with increased bleeding risk, and 0.80 (0.65–0.98) for patients with renal impairment (Figure). Conclusion In the selected common challenging scenarios of AF patients, there were significant mortality reductions in favor of NOACs compared to VKAs. These observations suggest that NOACs are safe and effective in patients who are elderly, at increased bleeding risk, or renally impaired. FUNDunding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): This study was supported by an unrestricted research grant from Bayer AG, Berlin, Germany, to TRI, London, UK, which sponsors the GARFIELD-AF registry. The work is supported by KANTOR CHARITABLE FOUNDATION for the Kantor-Kakkar Global Centre for Thrombosis Science.

Pattern and Management of Intracranial Haemorrhage with Rivaroxaban or Dabigatran Compared to Vitamin K Antagonists - Results of the Prospective Dresden Noac Registry

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1127-1127
Author(s):  
Sandra Marten ◽  
Luise Tittl ◽  
Katharina Daschkow ◽  
Jan Beyer-Westendorf
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Research Funding ◽  
Intracranial Haemorrhage ◽  
Vitamin K Antagonists ◽  
Bleeding Risk ◽  
Interventional Therapy ◽  
Phase Iii ◽  
Bayer Healthcare ◽  
Phase Iii Trials

Abstract Background: In recent phase-III trials, the rate of intracranial haemorrhage (ICH) - the most feared complication of anticoagulant therapy - was around 0.8% per year for patients treated with vitamin K antagonists (VKA) and consistently lower (around 0.3-0.5%) for patients treated with the non-VKA oral anticoagulants (NOACs) rivaroxaban and dabigatran However, patients in clinical trials present a selected population treated under a strict protocol in dedicated academic facilities. Consequently, the risk, management and outcome of ICH need to be evaluated in cohorts of patients treated with NOACs or VKA in daily care. Aim: To evaluate the rate of ICH in patients treated with NOAC compared to VKA patients. Patients and methods: The prospective NOAC registry was initiated in November 2011. A network of more than 230 physicians in the district of Saxony, Germany, enrol up to 3000 patients in the registry, which are prospectively followed by the central registry office for up to 60 months with central outcome event adjudication. For this analysis, every intracranial haemorrhage was identified in the database and ICH management and outcome were evaluated. Results: Until January 31th 2015, 2682 patients were registered and treated with dabigatran (348, mostly treated for atrial fibrillation), Rivaroxaban (1907; 1204 treated for atrial fibrillation and 703 for venous thromboembolism) or vitamin K antagonists (427; treated for atrial fibrillation). VKA patients had lower HAS-BLED scores compared to NOAC patients and were excellently managed with a time-in-therapeutic-range of 75%. During follow-up (mean follow-up duration 25.6 months) ICH occurred in 7/427(1.6%) of VKA treated patients and in 14/2255 (0.6%) of patients treated with NOAC, which translated into an annualized rate of 1.3 events/100 pt. years (95%-CI 0.5-2.7) for VKA and 0.4 events/100 pt. years (95%-CI 0.2-0.6) for NOAC (p=0.0039). Treatment of ICH consisted of PCC in 10 cases, plasma in 3 cases and surgical or interventional therapy in 7 cases (table 1, multiple treatments possible). As indicated, use of factor concentrates, plasma or other hemostatic agents or surgery was much more frequent in VKA patients compared to NOAC patients. Table 1. Cause and treatment of ICH ICH/total Spontaneous vs. traumatic ICH (n) treatment with PCC treatment with fresh frozen plasma treatment with other hemostatic agents no hemostatic treatment surgical or interventional therapy dabigatran 2/348 (0.6%) 2 vs. 0 0 0 0 2/2 (100%) 1/2 (50%) rivaroxaban 12/1907 (0.6%) 4 vs. 8 5/12 (41.7%) 2/12 (16.7%) 2/12 (16.7%) 7/12 (58.3%) 3/12 (25%) VKA 7/427 (1.6%) 2 vs. 5 5/7 (71.4%) 1/7 (14.3%) 4/7 (57.1%) 2/7 (28.6%) 3/7 (42.9%) At Day 90 after ICH, 7/21 patients were dead (2/7 or 28.6% of VKA patients and 5/14 or 35.7% of NOAC patients). The surviving 14 patients received the following antithrombotic agents: 5 (35.7%) rivaroxaban, 3 (21.4%) heparin, 1 (7.1%) apixaban, 1 (7.1%) VKA, 3 (21.4%) aspirin, 1 (7.1%) none.Following ICH, oral anticoagulation therapy was either interrupted (n=7; 6 NOAC vs. 1 VKA) or permanently discontinued (n=10; 6 NOAC vs. 4 VKA). Conclusion: Despite low bleeding risk and excellent INR control in our VKA cohort, the rate of ICH was higher than that of VKA patients treated in recent phase-III trials. Furthermore, ICH rates in our VKA cohort were significantly higher than those seen in our NOAC cohorts, which represented more patients with relevant comorbidities and higher bleeding risk. Consequently, the risk of ICH remains high even in "stable" VKA patients with good INR control and a preventive switch from VKA to NOAC may help to reduce ICH risk and should be discussed with the patient. Disclosures Marten: Bayer HealthCare: Honoraria. Beyer-Westendorf:Pfizer: Honoraria, Research Funding; Boehringer Ingelheim: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Bayer HealthCare: Honoraria, Research Funding.

P4783Treatment persistence of patients with atrial fibrillation on VKA or NOAC: Data from GLORIA-AF Phase III 1-year interim analysis

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
G Y H Lip ◽  
H.-C Diener ◽  
S J Dubner ◽  
J L Halperin ◽  
K J Rothman ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Interim Analysis ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Phase Iii ◽  
Treatment Persistence ◽  
Geographical Regions ◽  
Dosing Regimens ◽  
The Impact

Abstract Background Oral anticoagulation (OAC) persistence is important for optimizing stroke prevention in patients with atrial fibrillation (AF); non-vitamin K oral anticoagulants (NOACs) generally show better persistence than vitamin K antagonists (VKAs), while the impact of dosing regimens remains unclear. We compared treatment persistence of NOACs and VKAs, and of NOAC dosing regimens in the prospective GLORIA-AF registry program. Methods Patients newly diagnosed with AF were enrolled in Phase III of GLORIA-AF (2014–2016) from 4 geographical regions (North America [NA], Europe, Asia and Latin America). Treatment persistence after 1 year for i) NOAC (dabigatran, rivaroxaban, apixaban, edoxaban) vs VKA, and ii) twice daily (bid, dabigatran, apixaban) vs once daily (od; rivaroxaban, edoxaban) NOAC treatment was analysed using multivariable Cox analysis; propensity score trimming was used to reduce bias due to unmeasured confounders. Missing data was handled by multiple imputation. Results Overall, 21,592 patients were enrolled (4970 [23%] patients on VKAs, 12,797 [59%] on NOACs, 2391 [11%] on antiplatelets, and 1426 [6.6%] received no therapy; 8 [0.04%] received other treatment). After trimming, 11,935 and 4484 patients treated with NOACs and VKAs, respectively, were compared. NOACs had better treatment persistence than VKAs (discontinuation hazard ratio [HR]=0.75, 95% confidence interval [CI] 0.69–0.81). Other relevant associations were decreased OAC persistence for symptomatic AF, NA and Asia regions (Table). There was no difference in treatment persistence for patients on a bid (N=7842) vs od (N=4098) NOAC (discontinuation HR=0.94, 95% CI 0.86–1.02). Conclusion In this 1-year interim analysis of GLORIA-AF Phase III, treatment persistence was improved with NOACs vs VKAs, whereas for NOACs, dosing regimen (bid vs od) had no impact on treatment persistence. Acknowledgement/Funding The GLORIA-AF Registry program was funded by Boehringer-Ingelheim

scholarly journals Novel Anticoagulants for Atrial Fibrillation

Angiology ◽  
2011 ◽  
Vol 63 (3) ◽  
pp. 164-170 ◽  
Author(s):  
Stylianos Tzeis ◽  
George Andrikopoulos
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Preventive Treatment ◽  
Phase Iii ◽  
Coagulation Cascade ◽  
Considerable Proportion ◽  
Novel Anticoagulants ◽  
Increased Risk ◽  
Reduced Rate

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with an increased risk of thromboembolic complications and stroke. Therefore, the implementation of thromboembolic preventive treatment is the cornerstone of quality management in AF patients. During the last 60 years, vitamin K antagonists remain at the forefront of antithrombotic management of AF patients. Randomized trials have demonstrated their superiority over aspirin as well as over the combination of aspirin and clopidogrel with similar safety profile. However, the disseminated use of vitamin K antagonists among suitable candidates is hampered by their inherent limitations. As a result, a considerable proportion of AF patients do not receive this life-saving therapy. In the last few years, novel anticoagulants targeting factors IIa (dabigatran) and Xa (rivaroxaban, apixaban, edoxaban) in the coagulation cascade have been developed. Recently completed phase III mega-trials of dabigatran, rivaroxaban and apixaban have provided cumulative evidence in favor of these novel anticoagulants. Their main advantages, apart from their treatment efficacy, include the reduced rate of intracranial hemorrhage, the lack of need for routine coagulation monitoring, the predictable anticoagulation response and the limited interaction with food and drugs. In the present manuscript we present a critical appraisal of the recent trials focusing on issues that are expected to influence decision making on selection of novel anticoagulants.

scholarly journals The safety of new oral anticoagulants for ischemic stroke and systemic embolism prevention in females with atrial fibrillation

2021 ◽  
Vol 20 (1) ◽  
pp. 5-14
Author(s):  
Despina-Manuela Toader ◽  
◽  
Ileana Neaca ◽  
Alina Paraschiv ◽  
Rodica Musetescu ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Oral Anticoagulants ◽  
Bleeding Risk ◽  
Vitamin K Antagonist ◽  
Phase Iii ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Factor X ◽  
Systemic Embolism

The prevalence of atrial fibrillation is lower in females than in men, but the risk of stroke and systemic thromboembolism is comparable or even higher. Administration of anticoagulant therapy does not modify this difference. Two classes of non-vitamin K antagonist oral anticoagulants were studied in atrial fibrillation: direct thrombin inhibitors, like Dabigatran, and activated factor X inhibitors, like Rivaroxaban, Apixaban and Edoxaban. Response to oral anticoagulants could differ between the gender. This medication was evaluated in phase III randomized controlled trials. Non-vitamin K antagonist oral anticoagulants have been proved more efficacious than Warfarin for stroke and systemic embolism prevention in women, but conclusions regarding the safety and the bleeding are heterogeneous. As in men, before prescribing a NOAC to a female with AF, the stroke and the bleeding risk have to be carefully estimated. It is important that future studies to be targeted on comparison between of non-vitamin K antagonist oral anticoagulants versus Warfarin in females with non-valvular atrial fibrillation.

scholarly journals Falls in ED patients: do elderly patients on direct oral anticoagulants bleed less than those on vitamin K antagonists?

2021 ◽  
Vol 29 (1) ◽  
Author(s):  
Martin Müller ◽  
Ioannis Chanias ◽  
Michael Nagler ◽  
Aristomenis K. Exadaktylos ◽  
Thomas C. Sauter
Keyword(s):  
Elderly Patients ◽  
Vitamin K ◽  
Intracranial Haemorrhage ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Bleeding Complications ◽  
Lower Odds ◽  
Anticoagulated Patients ◽  
Proportional Incidence

Abstract Background Falls from standing are common in the elderly and are associated with a significant risk of bleeding. We have compared the proportional incidence of bleeding complications in patients on either direct oral anticoagulants (DOAC) or vitamin K antagonists (VKA). Methods Our retrospective cohort study compared elderly patients (≥65 years) on DOAC or VKA oral anticoagulation who presented at the study site – a Swiss university emergency department (ED) – between 01.06.2012 and 01.07.2017 after a fall. The outcomes were the proportional incidence of any bleeding complication and its components (e.g. intracranial haemorrhage), as well as procedural and clinical parameters (length of hospital stay, admission to intensive care unit, in-hospital-mortality). Uni- and multivariable analyses were used to compare the studied outcomes. Results In total, 1447 anticoagulated patients were included – on either VKA (n = 1021) or DOAC (n = 426). There were relatively more bleeding complications in the VKA group (n = 237, 23.2%) than in the DOAC group (n = 69, 16.2%, p = 0.003). The difference persisted in multivariable analysis with 0.7-fold (95% CI: 0.5–0.9, p = 0.014) lower odds for patients under DOAC than under VKA for presenting with any bleeding complications, and 0.6-fold (95% 0.4–0.9, p = 0.013) lower odds for presenting with intracranial haemorrhage. There were no significant differences in the other studied outcomes. Conclusions Among elderly, anticoagulated patients who had fallen from standing, those under DOACs had a lower proportional incidence of bleeding complications in general and an even lower incidence of intracranial haemorrhage than in patients under VKAs.

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