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Atrial fibrillation and comorbidities: Clinical characteristics and antithrombotic treatment in GLORIA-AF.
Kozieł, M, Teutsch, C, Halperin, JL, Rothman, KJ, Diener, HC, Ma, CS, Marler, S, Lu, S, Gurusamy, VK, Huisman, MV, et al
PloS one. 2021;(4):e0249524
Abstract
BACKGROUND Patients with AF often have multimorbidity (the presence of ≥2 concomitant chronic conditions). OBJECTIVE To describe baseline characteristics, patterns of antithrombotic therapy, and factors associated with oral anticoagulant (OAC) prescription in patients with AF and ≥2 concomitant, chronic, comorbid conditions. METHODS Phase III of the GLORIA-AF Registry enrolled consecutive patients from January 2014 through December 2016 with recently diagnosed AF and CHA2DS2-VASc score ≥1 to assess the safety and effectiveness of antithrombotic treatment. RESULTS Of 21,241 eligible patients, 15,119 (71.2%) had ≥2 concomitant, chronic, comorbid conditions. The proportions of patients with multimorbidity receiving non-vitamin K antagonist oral anticoagulants (NOACs) and vitamin K antagonists (VKA) were 60.2% and 23.6%, respectively. The proportion with paroxysmal AF was 57.0% in the NOAC group and 45.4% in the VKA group. Multivariable log-binomial regression analysis found the following factors were associated with no OAC prescription: pattern of AF (paroxysmal, persistent, or permanent), coronary artery disease, myocardial infarction, prior bleeding, smoking status, and region (Asia, North America, or Europe). Factors associated with OAC prescriptions were age, body mass index, renal function, hypertension, history of cerebral ischemic symptoms, and AF ablation. CONCLUSION Multimorbid AF patients prescribed NOACs have fewer comorbidities than those prescribed VKAs. Age, AF pattern, comorbidities, and renal function are associated with OAC prescription.
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Daily Supplementation of L-Glutamine in Atrial Fibrillation Patients: The Effect on Heat Shock Proteins and Metabolites.
Starreveld, R, Ramos, KS, Muskens, AJQM, Brundel, BJJM, de Groot, NMS
Cells. 2020;(7)
Abstract
Pharmaco-therapeutic strategies of atrial fibrillation (AF) are moderately effective and do not prevent AF onset and progression. Therefore, there is an urgent need to develop novel therapies. Previous studies revealed heat shock protein (HSP)-inducing compounds to mitigate AF onset and progression. Such an HSP inducing compound is L-glutamine. In the current study we investigate the effect of L-glutamine supplementation on serum HSP27 and HSP70 levels and metabolite levels in patients with AF patients (n = 21). Hereto, HSP27 and HSP70 levels were determined by ELISAs and metabolites with LC-mass spectrometry. HSP27 levels significantly decreased after 3-months of L-glutamine supplementation [540.39 (250.97-1315.63) to 380.69 (185.68-915.03), p = 0.004] and normalized to baseline levels after 6-months of L-glutamine supplementation [634.96 (139.57-3103.61), p < 0.001]. For HSP70, levels decreased after 3-months of L-glutamine supplementation [548.86 (31.50-1564.51) to 353.65 (110.58-752.50), p = 0.045] and remained low after 6-months of L-glutamine supplementation [309.30 (118.29-1744.19), p = 0.517]. Patients with high HSP27 levels at baseline showed normalization of several metabolites related to the carbohydrates, nucleotides, amino acids, vitamins and cofactors metabolic pathways after 3-months L-glutamine supplementation. In conclusion, L-glutamine supplementation reduces the serum levels of HSP27 and HSP70 within 3-months and normalizes metabolite levels. This knowledge may fuel future clinical studies on L-glutamine to improve cardioprotective effects that may attenuate AF episodes.
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Educational Impact on Apixaban Adherence in Atrial Fibrillation (the AEGEAN STUDY): A Randomized Clinical Trial.
Montalescot, G, Brotons, C, Cosyns, B, Crijns, HJ, D'Angelo, A, Drouet, L, Eberli, F, Lane, DA, Besse, B, Chan, A, et al
American journal of cardiovascular drugs : drugs, devices, and other interventions. 2020;(1):61-71
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Abstract
INTRODUCTION Adherence to non-vitamin-K oral anticoagulants (NOACs) may be lower than to vitamin K antagonists because NOACs do not require routine monitoring. OBJECTIVE We assessed the impact of an educational program on adherence and persistence with apixaban in patients with non-valvular atrial fibrillation (NVAF). METHODS Patients with NVAF eligible for NOACs with one or more stroke risk factor (prior stroke/transient ischemic attack, age ≥ 75 years, hypertension, diabetes, or symptomatic heart failure) were randomized (1:1) to standard of care (SOC) or SOC with additional educational (information booklet, reminder tools, virtual clinic access). The primary outcome was adherence to apixaban (2.5 or 5 mg twice daily) at 24 weeks. Patients receiving the educational program were re-randomized (1:1) to continue the program for 24 further weeks or to switch to secondary SOC. Implementation adherence and persistence were reassessed at 48 weeks. RESULTS In total, 1162 patients were randomized (SOC, 583; educational program, 579). Mean implementation adherence ± standard deviation (SD) at 24 weeks was 91.6% ± 17.1 for SOC and 91.9% ± 16.1 for the educational program arm; results did not differ significantly between groups at any time-point. At 48 weeks, implementation adherence was 90.4% ± 18.0, 90.1% ± 18.6, and 89.3% ± 18.1 for continued educational program, SOC, and secondary SOC, respectively; and corresponding persistence was 86.1% (95% confidence interval [CI] 81.3-89.7), 85.2% (95% CI 81.5-88.2), and 87.8% (95% CI 83.4-91.1). Serious adverse events were similar across groups. CONCLUSION High implementation adherence and persistence with apixaban were observed in patients with NVAF receiving apixaban. The educational program did not show additional benefits. CLINICAL TRIAL REGISTRATION This study is registered at ClinicalTrials.gov [NCT01884350].
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Ivabradine for chronic heart rate control in persistent atrial fibrillation. Design of the BRAKE-AF project.
Fontenla, A, López-Gil, M, Tamargo-Menéndez, J, Matía-Francés, R, Salgado-Aranda, R, Rey-Blas, JR, Miracle-Blanco, Á, Mejía-Martínez, E, Pastor-Fuentes, A, Toquero-Ramos, J, et al
Revista espanola de cardiologia (English ed.). 2020;(5):368-375
Abstract
INTRODUCTION AND OBJECTIVES Ivabradine is an inhibitor of the If channel, the main determinant of the pacemaker function of the sinus node. The drug has been approved for the treatment of angina and heart failure. There is some evidence of its role as an inhibitor of atrial-ventricular node (AVN) conduction. The aim of the BRAKE-AF project is to assess ivabradine use for rate control in atrial fibrillation (AF). METHODS A multicenter, randomized, parallel, open-label, noninferiority phase III clinical trial will be conducted to compare ivabradine vs digoxin in 232 patients with uncontrolled permanent AF despite beta-blockers or calcium channel blockers. The primary efficacy endpoint is the reduction in daytime heart rate measured by 24-hour Holter monitoring at 3 months. This clinical trial will be supported by an electrophysiological study of the effect of ivabradine on the action potential of the human AVN. To do this, an experimental model will be used with Chinese hamster ovarium cells transfected with the DNA encoding the expression of the t channels involved in this action potential and recording of the ionic currents with patch clamp techniques. RESULTS New data will be obtained on the effect of ivabradine on the human AVN and its safety and efficacy in patients with permanent AF. CONCLUSIONS The results of the BRAKE-AF project might allow inclusion of ivabradine within the limited arsenal of drugs currently available for rate control in AF. CLINICAL TRIAL REGISTRATION http://www.clinicaltrials.gov. Identifier: NCT03718273.
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Impact of a Computerized Antithrombotic Risk Assessment Tool on the Prescription of Thromboprophylaxis in Atrial Fibrillation: Hospital Setting.
Pandya, E, Masood, N, Wang, Y, Krass, I, Bajorek, B
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2018;(1):85-92
Abstract
The computerized antithrombotic risk assessment tool (CARAT) is an online decision-support algorithm that facilitates a systematic review of a patient's stroke risk, bleeding risk, and pertinent medication safety considerations, to generate an individualized treatment recommendation. The CARAT was prospectively applied across 2 hospitals in the greater Sydney area. Its impact on antithrombotics utilization for thromboprophylaxis in patients with nonvalvular atrial fibrillation was evaluated. Factors influencing prescribers' treatment selection were identified. The CARAT recommended a change in baseline therapy for 51.8% of patients. Among anticoagulant-eligible patients (ie, where the risk of stroke outweighed the risk of bleeding) using "nil therapy" or antiplatelet therapy at baseline, the CARAT recommended an upgrade to warfarin in 60 (30.8%) patients. For those in whom the bleeding risk outweighed the stroke risk, the CARAT recommended a downgrade from warfarin to safer alternatives (eg, aspirin) in 37 (19%) patients. Among the "most eligible" (ie, high stroke risk, low bleeding risk, no contraindications; n = 75), the CARAT recommended warfarin for all cases. Discharge therapy observed a marginal increase in anticoagulation prescription in eligible patients (n = 116; 57.8% vs 64.7%, P = .35) compared to baseline. Predictors of warfarin use (vs antiplatelets) included congestive cardiac failure, diabetes mellitus, and polypharmacy. The CARAT was able to optimize the selection of therapy, increasing anticoagulant use among eligible patients. With the increasing complexity of decision-making, such tools may be useful adjuncts in therapy selection in atrial fibrillation. Future studies should explore the utility of such tools in selecting therapies from within an expanded treatment armamentarium comprising the non-vitamin K antagonist oral anticoagulants.
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Use of dabigatran and rivaroxaban in non-valvular atrial fibrillation: one-year follow-up experience in an Italian centre.
Schiavoni, M, Margaglione, M, Coluccia, A
Blood transfusion = Trasfusione del sangue. 2018;(2):209-214
Abstract
BACKGROUND Direct oral anticoagulants (DOAC) have been shown to be non-inferior to traditional vitamin K antagonists in preventing stroke and arterial thromboembolism in patients with non-valvular atrial fibrillation. Nevertheless, it is mandatory to record side effects and individual adherence to DOAC treatment. MATERIALS AND METHODS In this single-centre experience, patients with non-valvular atrial fibrillation were prospectively observed after switching from a vitamin K antagonist to dabigatran or rivaroxaban. The efficacy, safety, and tolerability of the novel treatment, and adherence to it, were evaluated over a period of 1 year. Clinical data were integrated with records of haemorrhagic and non-haemorrhagic complications. All the subjects were given an anonymous self-report questionnaire on the degree of their adherence/satisfaction with the treatment. RESULTS Of 196 patients with non-valvular atrial fibrillation (median age, 78.5 years) who switched from a vitamin K antagonist to DOAC, 178 completed the 1-year follow up, of whom 87 were given dabigatran and 91 rivaroxaban. The efficacy of the two DOAC was similar. Patients given dabigatran had a higher frequency (n=32) of non-haemorrhagic complications (OR: 3.3; 95% CI: 1.7-7.8), which occurred earlier (HR: 6.1; 95% CI: 3.0-12.6) than those (n=7) recorded in subjects on rivaroxaban. The degree of satisfaction with therapy was higher among patients on rivaroxaban (mean score 9.1, SD 1.0) than among those on dabigatran (mean score 8.7; SD 0.9; p=0.01). DISCUSSION Overall, in this experience, DOAC were shown to be effective, safe alternatives to vitamin K antagonists. Nevertheless, compared with rivaroxaban, dabigatran resulted in a higher rate and earlier occurrence of non-haemorrhagic events, and a lower satisfaction score.
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Comparison of clinical characteristics of real-life atrial fibrillation patients treated with vitamin K antagonists, dabigatran, and rivaroxaban: results from the CRAFT study.
Balsam, P, Ozierański, K, Tymińska, A, Żukowska, K, Zaleska, M, Szepietowska, K, Maciejewski, K, Peller, M, Grabowski, M, Lodziński, P, et al
Kardiologia polska. 2018;(5):889-898
Abstract
BACKGROUND The first-line drugs for the treatment of non-valvular atrial fibrillation (AF) are non-vitamin K antagonist oral anticoagulants (NOACs), which are preferred over vitamin K antagonists (VKAs). There is some evidence that there are dis-crepancies between everyday clinical practice and the guidelines. AIM: The study aimed to compare the characteristics of patients on VKAs, dabigatran, and rivaroxaban in everyday practice (i.e. baseline characteristics, drug doses, risk factors for bleeding and thromboembolic events). Additionally, we assessed the frequency of prescription of different oral anticoagulants (OACs) in recent years. METHODS This study consisted of data from the multicentre CRAFT (MultiCentre expeRience in AFib patients Treated with OAC) study (NCT02987062). This was a retrospective analysis of hospital records of AF patients (hospitalised in the years 2011-2016) treated with VKAs (acenocoumarol, warfarin) and NOACs (dabigatran, rivaroxaban). A total of 3528 patients with non-valvular AF were enrolled in the CRAFT study. RESULTS The total cohort consisted of 1973 patients on VKA, 504 patients on dabigatran, and 1051 patients on rivaroxaban. Patients on rivaroxaban were older (70.5 ± 13.1 years) and more often female (47.9%), compared with those on VKAs (67.0 ± 12.8 years, p < 0.001; 35.5%, p < 0.001) and on dabigatran (66.0 ± 13.9 years, p < 0.001; 38.9%, p = 0.001). Among NOACs, patients with persistent and permanent AF were more likely to receive rivaroxaban (54.7% and 73.4%, re-spectively) than dabigatran (45.3%, p < 0.001 and 26.6%, p = 0.002, respectively). Patients on rivaroxaban had higher risk of thromboembolic events (CHA2DS2VASc 3.9 ± 2.0, CHADS2 2.2 ± 1.4) than those on VKAs (3.3 ± 2.0, 1.9 ± 1.3) and on dabigatran (3.1 ± 2.0, 1.8 ± 1.3). Patients on rivaroxaban had also a higher rate of prior major bleeding (11.2%) than those on VKAs (6.7%, p < 0.001) and on dabigatran (7.3%, p = 0.02). Patients on lower doses of dabigatran and rivaroxaban had a significantly higher risk of thromboembolic and bleeding events. Use of VKAs in the year 2011 was reported in over 96% of patients on OACs, but this proportion decreased to 34.6% in 2016. In the last analysed year (2016) AF patients were treated mainly with NOACs - dabigatran (24.2%) and rivaroxaban (41.3%). CONCLUSIONS The prescription of VKAs declined significantly after the introduction of NOACs. Patients treated with different OACs demonstrated a distinct baseline clinical profile. The highest risk of thromboembolic events and incidence of major bleedings was observed in patients on rivaroxaban, in comparison to patients on VKAs and dabigatran. Among NOACs, patients treated with lower doses of dabigatran and rivaroxaban were older and had a significantly higher risk of thromboembolic and bleeding events.
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Incidence of left atrial abnormalities under treatment with dabigatran, rivaroxaban, and vitamin K antagonists.
Reers, S, Agdirlioglu, T, Kellner, M, Borowski, M, Thiele, H, Waltenberger, J, Reppel, M
European journal of medical research. 2016;(1):41
Abstract
BACKGROUND Non-vitamin K antagonist oral anticoagulants (NOACs) such as dabigatran or rivaroxaban are alternatives to vitamin K antagonists (VKAs) for prevention of stroke and systemic embolism in patients with atrial fibrillation (AF) and atrial flutter (AFL). Incidences of risk factors for left atrium (LA) and left atrial appendage (LAA) thrombus formation, such as dense spontaneous echo contrast (SEC), low LAA velocity (LAAV) <20 cm/s under treatment with dabigatran and rivaroxaban in comparison with VKAs are unknown. METHODS We studied 306 patients with AF (94 %) and AFL (6 %) undergoing transesophageal echocardiography. Patients received VKAs (n = 138), dabigatran (n = 68), or rivaroxaban (n = 100) for at least 3 weeks prior to investigation. Time in therapeutic range was 67 % for VKA. Mean CHADS2 score and CHA2DS2-VASc score were 1.3 and 2.5, respectively. Left atrial abnormality was defined as either dense SEC, low LAAV <20 cm/s, or thrombus. RESULTS Any LA abnormality occurred in 9, 3, and 5 % of patients receiving VKA, dabigatran, and rivaroxaban, respectively. The most frequent abnormality was LAA thrombus (VKA: 4 %, dabigatran: 0 %, rivaroxaban: 2 %) and low LAAV of less than 20 cm/s (VKA: 4 %, dabigatran: 1 %, rivaroxaban: 1 %), followed by dense SEC (VKA: 2 %, dabigatran: 1 %, rivaroxaban: 2 %). Results of uni- and multivariate analyses revealed a numerically lower but not significantly different frequency of any LA abnormality under dabigatran (OR 0.4, 95 % Cl 0.08 - 1.88, p = 0.25) and rivaroxaban (OR 0.65, 95 % Cl 0.22 - 1.98, p = 0.45) compared to VKA. CONCLUSION With respect to the incidence of LA abnormalities, dabigatran and rivaroxaban are not inferior to VKA.
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Effectiveness, safety and costs of thromboembolic prevention in patients with non-valvular atrial fibrillation: phase I ESC-FA protocol study and baseline characteristics of a cohort from a primary care electronic database.
Giner-Soriano, M, Vedia Urgell, C, Roso-Llorach, A, Morros, R, Capellà, D, Castells, X, Ferreira-González, I, Troncoso Mariño, A, Diògene, E, Elorza, JM, et al
BMJ open. 2016;(1):e010144
Abstract
PURPOSE Atrial fibrillation is the most common arrhythmia. Its management aims to reduce symptoms and to prevent complications through rate and rhythm control, management of concomitant cardiac diseases and prevention of related complications, mainly stroke. The main objective of Effectiveness, Safety and Costs in Atrial Fibrillation (ESC-FA) study is to analyse the drugs used for the management of the disease in real-use conditions, particularly the antithrombotic agents for stroke prevention. The aim of this work is to present the study protocol of phase I of the ESC-FA study and the baseline characteristics of newly diagnosed patients with atrial fibrillation in Catalonia, Spain. PARTICIPANTS The data source is System for the Improvement of Research in Primary Care (SIDIAP) database. The population included are all patients with non-valvular atrial fibrillation diagnosis registered in the electronic health records during 2007-2012. FINDINGS TO DATE A total of 22,585 patients with non-valvular atrial fibrillation were included in the baseline description. Their mean age was 72.8 years and 51.6% were men. The most commonly prescribed antithrombotics were vitamin K antagonists (40.1% of patients) and platelet aggregation inhibitors (32.9%); 25.3% had not been prescribed antithrombotic treatment. Age, gender, comorbidities and co-medication at baseline were similar to those reported for previous studies. FUTURE PLANS The next phase in the ESC-FA study will involve assessing the effectiveness and safety of antithrombotic treatments, analysing stroke events and bleeding episodes' rates in our patients (rest of phase I), describing the current management of the disease and its costs in our setting, and assessing how the introduction of new oral anticoagulants changes the stroke prevention in non-valvular atrial fibrillation.
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Clinical safety, tolerability, pharmacokinetics and pharmacodynamics of the novel factor Xa inhibitor DY-807f in healthy volunteers.
Ogata, K, Shimizu, T, Masumoto, H, Oguma, T, Sugiyama, N, Kunitada, S
Thrombosis research. 2015;(4):594-601
Abstract
INTRODUCTION Since Vitamin K antagonists are associated with various limitations such as narrow therapeutic window, slow onset and offset of effect, and numerous interactions with food and drugs, new oral anticoagulants targeted to inhibit thrombin or factor Xa (FXa) have been developed. DY-807f is a highly selective, reversible and orally bioavailable FXa inhibitor. OBJECTIVES This article describes a first-in-human study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single ascending oral doses of the novel direct FXa inhibitor DY-807f in healthy males. METHODS a placebo-controlled, single-blinded, randomized, single ascending dose study with 84 subjects (10, 30, 60, 120, 240, and 360 mg). Effects of food and formulation (tablet vs solution) on bioavailability of 60 mg were also assessed as a crossover design. RESULTS DY-807f doses were safe and well-tolerated with no dose-dependent increase in adverse events up to 360 mg. Pharmacokinetics profiles were consistent across doses with rapid absorption, biphasic elimination, and terminal elimination half-life of 10.5 to 12.4 hours. Coagulation parameters (Activated Partial Thromboplastin Time (aPTT) and Prothrombin Time (PT)) were linearly correlated with plasma DY-807 (free base of DY-807f) concentrations (correlation coefficient: 0.786 for aPTT, 0.945 for PT). CONCLUSIONS Single doses of DY-807f are safe and well-tolerated up to 360 mg with predictable pharmacokinetic and pharmacodynamic profiles.