New Oral Anticoagulants Therapy Research Articles

#3896 SAFETY OUTCOMES OF ORAL ANTICOAGULANT THERAPY IN PATIENTS WITH ATRIAL FIBRILLATION AND CHRONIC KIDNEY DISEASE

Abstract Background and Aims The comorbid conditions of atrial fibrillation (AF) and chronic kidney disease (CKD) leads to an increased risk of thromboembolic complications, but on the other hand is a risk factor for various bleeding. Oral anticoagulant therapy is the standard for the prevention of thromboembolic complications in AF. But with the deterioration of kidney function, the risk of hemorrhagic complications increases dramatically. This problem makes it difficult to choose an effective and safe oral anticoagulant therapy. Clinical data on the use of new oral anticoagulants (NOACs) in patients with AF and advanced CKD are limited, which determines the relevance of conducting studies in comparison with vitamin K antagonists. The aim of study was evaluation of safety parameters for the using of rivaroxaban in patients with stage 4 CKD with AF. Method The study included 109 patients over the age of 18 with a diagnosis of stage 4 CKD (eGFR – 15–29 ml/min/1.72 m2) and non-valvular AF. They were randomized in a 2:1 ratio to either rivaroxaban 15 mg (n = 73) or warfarin (n = 36). The mean follow-up period was 18 months. In the warfarin group, time in therapeutic range (TTR) >70% was achieved in 34 (94%) patients. Exclusion criteria were a history of bleeding that required hospitalization; decrease in hemoglobin level below 80 g/l, platelet count below 100 × 109/l; indications for taking antiplatelet therapy; chronic use of drugs that increase the risk of bleeding. The analysis of the observed hemorrhagic events was carried out using the BARC and ISTH scales. Classification of anemia was carried out according to the recommendations of the World Health Organization. Results Patients taking warfarin were significantly more likely to develop minor bleeding according to the BARC scales and ISTH and all clinically significant bleeding on the ISTH scale. In patients with AF and CKD receiving warfarin therapy, minor bleeding (MB) according to the BARC scale was observed in 72.2% (n = 26), minor clinically significant bleeding (MCSB) in 8.33% (n = 3), major bleeding in 8.33% (n = 3) of cases; and in the group of patients treated with rivaroxaban, MB was observed in 42.4% (n = 31, p<0.01), MCSB in 2.74% (n = 2, p = 0.32), major bleeding in 2.74% (n = 2, p = 0.32) of cases. When assessing bleeding on the ISTH scale during therapy with VKA, MB – 61.1% (n = 22), MCSB – 19.4% (n = 7), major bleeding – 8.33% (n = 3); against the background of NOACs therapy, MB – 36.9% (n = 27, p = 0.01), MCSB in 8.2% (n = 6, p = 0.06), major bleeding in 2.74% (n = 2, p = 0.32). All clinically significant hemorrhagic events according to the BARC scale in the warfarin group occurred more than 16.6% (n = 6) compared with the rivaroxaban group 5.4% (n = 4, p = 0.06); when analyzed according to the ISTH scale, the number of patients receiving VKA anticoagulant therapy 27.7% (n = 10) significantly prevailed over patients on the background of NOACs 10.9% (n = 8, p = 0.03). Analysis of hemoglobin level did not reveal significant dynamics and significant differences between the groups: the median hemoglobin level at inclusion was 129 g/l in the rivaroxaban group and 123 g/l in the warfarin group (p = 0.3), after 18 months - 130 g/l and 121 g/l, respectively (p = 0.7). Conclusion Data suggesting a favorable safety profile for NOACs (rivaroxaban) compared with VKAs (warfarin) in patients with AF and advanced CKD was obtained in this study. Taking rivaroxaban was accompanied by a significantly lower number of hemorrhagic events, which may indicate a safe effect of the drug. No significant changes in hemoglobin levels were found in both groups. Confirmation of these data may be key in choosing an anticoagulant in patients with AF and advanced CKD.

Возможности защиты желудочно-кишечного тракта при применении пероральных антикоагулянтов прямого действия у пациентов с фибрилляцией предсердий

Gastrointestinal bleeding (GIB) associated with the use of direct oral anticoagulants or, as they are also called, new oral anticoagulants (NOAC) is a serious medical problem, the relevance of which will only increase taking into account the constant expansion of the use of anticoagulants. It is especially important that most of the patients receiving NOAC are elderly people with multiple concomitant pathologies, including diseases of the gastrointestinal tract (GI), which makes them classified as patients with a high risk of GIB and, therefore, in need of prescribing gastroprotectors to protect the GI mucosa and prevent GIB. Considering that one of the mechanisms of GIB development during NOAC therapy is associated with their ability to inhibit GI mucosa healing, and the NOAC themselves are factors of aggression for GI and can lead to syndrome of increased epithelial permeability, the use of gastro- and the enteroprotector of rebamipide seems appropriate and probably pathogenetically justified. The randomized REGATA trial initiated at the Russian Gerontological Research and Clinical Center will provide additional information on the use of rebamipide in patients with atrial fibrillation receiving various NOAC.

Primary Non-adherence to Treatment with New Oral Anticoagulants: The Results of a Prospective Observational Study «ANTEY»

Aim: To assess the main characteristics of patients with non-valvular Atrial Fibrillation (AF) who are initially non-adherent to New Oral Anticoagulants (NOAC), and to identify factors associated with this version of non-adherence. Materials and Methods: The ANTEY study included 201 patients with non-valvular AF, who had indications and without contraindications for NOAC treatment. The patients had previously been advised to take oral anticoagulants but they did not comply with all medical recommendations. The observation period was 1 year, during which 2 in-person visits were performed: an inclusion visit (V0) and a visit (V1), as well as 1 telephone contact/follow up (FU); the interval between contacts was 6 months. All patients were recommended to take the NOAC by decision of the physician. During the V0, V1 and FU visits, the “National Society for Evidence-Based Pharmacotherapy (NSEPh) Adherence Scale” questionnaire was used to assess overall adherence and associated factors. 15 (7.5%) patients had not started NOAC therapy by the end of the study (primary non-adherent patients). Their characteristics are analysed in this work. Results: The main reasons for primary non-adherence to NOAC were high cost (33.3%), fears of adverse effects (AE) (33.3%), doubts about the need for treatment (13.3%) and the complex therapy regimen (13.3%). In the group of primary non-adherent patients in comparison with the rest of the patients there were significantly more patients with 1 point according to CHADS2VASc (20% and 2.2%, respectively, p = 0.029) and patients with 3 points according to HAS-BLED (33.3% and 9.1%, respectively, p = 0.006); they took antiplatelet drugs more often 73.3% versus 21.5%, respectively (p = 0.001). Full employment at work (OR = 5.2; CI95% [1.5; 18.1], p = 0.009), history of quitting smoking (OR = 5.1; CI95% [1.5; 17.0], p = 0,008), the presence of any pharmacotherapy AE (OR = 4.0; CI95% [1.01; 16.0], p = 0.048) increased the chance of primary non-adherence to NOAC by 4-5 times. Conclusion: The most vulnerable in relation to initiation of NOAC therapy for the prevention of thromboembolic complications in AF are those patients who continue to work or have any pharmacotherapy AE. The leading factors preventing the initiation of NOAC administration are their high cost, fear of the development of AE from the therapy, and patients’ doubts about the need for treatment with these drugs. The clinical trial registration number is NCT 03790917.

Short‐Term Cessation of Dabigatran Causes a Paradoxical Prothrombotic State

It is unclear if stopping treatment with dabigatran, a new oral anticoagulant (NOAC), induces a paradoxical rebound prothrombotic state. We investigated if short-term (1-3 days) dabigatran cessation is associated with a higher thrombus volume than expected from a simple reversal of the anticoagulant effect. Ten-week-old C57Bl/6 mice (n = 338) received one of the following oral treatments: phosphate-buffered saline (PBS), dabigatran for 7 days with or without 1 to 4 day cessation, and aspirin in either a single dose or daily for 7 days. Some of the animals that ceased dabigatran for 1 to 3 days received single-dose aspirin. Thereafter, we induced FeCl3 -mediated carotid thrombosis in 130 mice, after which we performed micro computed tomography thrombus imaging. The other 208 mice underwent coagulation assays or platelet function tests. As an explorative pilot study, we reviewed the medical records of 18 consecutive patients with NOAC cessation-related cerebral infarction in a large acute stroke cohort. We observed a ~ 40% higher volume of carotid thrombus after dabigatran cessation at 1 to 3 days than after vehicle treatment and showed that this effect could be prevented by single-dose aspirin pretreatment. Dabigatran cessation unduly increased platelet aggregability for 2 days after drug cessation, an effect mediated through thrombin or arachidonic acid, which effect was significantly attenuated by single-dose aspirin pretreatment. In patients, short-term (≤ 3 days) cessation of NOAC therapy, compared with longer-term (≥ 5 days) cessation, tended to be associated with relatively high stroke severity. We provide the first preclinical evidence that a rebound prothrombotic state follows short-term cessation of dabigatran therapy. ANN NEUROL 2021;89:444-458.

Main factors of adherence to new oral anticoagulants and its dynamics in outpatients with nonvalvular atrial fibrillation: results of the ANTEY study

Aim. To assess adherence to new oral anticoagulants (NOAC) or warfarin therapy and to study the factors influencing adherence in nonvalvular atrial fibrillation (AF) patients on different stages of treatment within the prospective outpatient registry of patients with cardiovascular diseases. Material and methods . The study included 201 patients with nonvalvular AF (males, 118 (58,7%)) from the outpatient registry PROFILE). Mean age was 71,1 ±8,7 years. Study protocol consisted of the inclusion visit (V0), 6-month follow-up visit (V1) and phone contact 1 year after V0 (PC). In V0, all patients were prescribed one of the NOACs. At V1 doctors could recommend warfarin or another NOAC to patients, who have refused taking prescribed NOAC. Medical adherence was determined using the of the National society of evidence-based pharmacotherapy (NSEPh) adherence scale. NSEPh adherence scale allows to grade patients’ adherence to treatment into 4 categories: 1) completely adherent, 2) partially adherent, 3) completely non-adherent, 4) partially non-adherent. Dichotomous grading into adherent (completely adherent) and non-adherent (rest of patients) was also used. Results. Out of 201 included patients, 200 came to V1 (1 patient died). PC was successful in 197 patients (3 patients died). According to NSEPh adherence scale, 155 (77,5%) patients at V1 were completely adherent, 5 (2,5%) — partially adherent, 7 (3,5%) — partially non-adherent, 33 (16,5%) — completely non-adherent. By the PC, 158 (80,2%) patients were completely adherent to the OAC therapy, 6 (3,0%) — partially adherent, 28 (14,2%) — partially non-adherent, 15 (7,6%) — completely non-adherent. At all stages of treatment, the following factors of good adherence remained significant: never-smoking, prior NOAC use, negative history of any treatment-related adverse effects (AEs). Patients with comorbidities and a history of bleeding during OAC therapy were more likely to discontinue initial scheme and violate treatment regimen (p<0,05). Symptomatic course of AF increased adherence by 2,4 times ( р =0,02). According to the questionnaire, the leading reasons for refusing NOAC therapy were the high cost of drugs, the fear of AE and doubts about the need for treatment. The main factors leading to discontinuation of NOAC/OAC treatment were bleeding and the cancellation (often unreasonable) of these medications by other doctors. Conclusion. The results of ANTEY study confirm that factors influencing adherence to NOAC may vary during different phases of treatment. The main reasons that prevent NOAC therapy initiation are the high cost of these drugs, fear of AE and doubts about the need for such treatment. Significant factors of discontinuation were AEs and cancellation of NOAC therapy by doctors from other medical institutions. Factors that positively affect both initiation and long-term use of the drug are never-smoking, prior NOAC use, negative history of any treatment-related AEs.

Chinese Survey on Enhanced Recovery after Surgery and Thromboprophylaxis Following Arthroplasty.

ObjectiveTo examine the current perspectives of enhanced recovery after surgery (ERAS) and the clinical practice applications of important ERAS principles among Chinese orthopaedic surgeons.MethodsThis was a cross‐sectional study using an online survey that was completed between November and December 2018. A 16‐item online questionnaire regarding the experiences of ERAS, perceptions of methods, and durations and concerns of venous thromboembolism (VTE) prophylaxis was sent to 2000 orthopaedic surgeons nationwide, and 1720 (86%) surgeons responded. Statistical analyses were conducted to assess all respondents' results and to compare differences among subgroups that were stratified according to city and hospital level, as well as their professional title.ResultsAccording to the results of the survey, ERAS awareness was high (65.1%) and most surgeons recognized the importance of thromboprophylaxis. However, the timing of ERAS was not consistent, with 22.8%, 31.9%, and 37.7% of surgeons choosing to initiate pharmaceutical prophylaxis within <6 h, 6–12 h, and 12–24 h after surgery, respectively. Low‐molecular‐weight heparin was mainly selected during hospitalization, and new oral anticoagulants (NOACs) were the first choice after discharge. Regarding postoperative antithrombotic therapy, particularly when combined with analgesics, the potential bleeding risk was mostly considered (80.0%)Tranexamic acid was believed to have no effect on the timing of NOAC therapy initiation (56.2%). Most of the above outcomes were influenced by the hospital level and professional title of the surgeon. Surgeons who had higher awareness on ERAS and better adhered to the guidelines were from higher‐level hospitals as well as had more advanced professional titles. City level partly might influence their practice but not impact surgeons' awareness.ConclusionsThe awareness and perception of the concept of ERAS and prophylactic antithrombotic regimens remain different among Chinese orthopaedic surgeons in different level cities and with various professional titles. Continuing medical educations (CME) on VTE prophylaxis is needed for improving the quality of health care in China.

The Efficacy, Safety and Adherence to Treatment when New Anticoagulants Taking in Over 75 Years Old Patients with Atrial Fibrillation

Aim. To study the efficacy, safety, and adherence to therapy with new oral anticoagulants in patients older than 75 years with atrial fibrillation.Material and methods. Patients (n=431) over 75 years old (82.7±3.4 years) with various types of atrial fibrillation/flutter (AF) were included in a nonrandomized observational study of new oral anticoagulants (NOAC) in real clinical practice. A history of cardiac surgery was in 27.6% of patients. All patients had &gt;3 risk factors for ischemic stroke (CHA2DS2-VASс 4.81±0.4 points) and &gt;1 risk factor for bleeding (HAS-BLED 3.01±0.2 points). The duration of the observation study was from 12 to 42 (26.9±4.9) months. Dabigatran was taken in 38.5% (n=166) of patients, rivaroxaban – in 41.3% (n=178), apixaban – in 20.2% (n=87) of patients.Results. The incidence of new cases of myocardial infarction was 0.8% per year, surgical revascularization – 0.9% per year, cardiovascular death – 0.8% per year. The frequency of ischemic stroke was 1.1% per year, transient ischemic attacks – 0.4% per year, all thromboembolic episodes – 1.77% per year. The incidence of intracranial hemorrhage was 0.2% per year, of minor bleeding – 4.4% per year, of the combined cardiac point (the total frequency of all strokes, major bleeding, myocardial infarction, mortality from cardiovascular causes, revascularization procedures) – 4.2% per year. Significant differences in the frequency of endpoints depending on the drug of NOAC taken by patients were not found. Violations of the regimen and doses were more often observed with twice daily intake (63.9% for dabigatran and 59.8% for apixaban) than with a single dosage regimen per day (45.5% for rivaroxaban). The leading causes of non-adherence to NOAC therapy in patients over 75 years of age included skipping the next scheduled dose (43.6%) and changing the frequency of the drug taking (16.9%). For NOAC with a double dose per day, dabigatran and apixaban, the frequency of administration was violated in 27.7% and 28.7%, respectively, and with a single dose per day, rivaroxaban – in 1.1%.Conclusion. Therapy with NOAC in patients older than 75 years with AF is effective and safe. There were no statistically significant differences in the incidence of thromboembolic or hemorrhagic events during three NOACs treatment in patients with AF older than 75 years. The incidence of non-adherence was less

Adherence to Treatment with New Oral Anticoagulants in Atrial Fibrillation Patients in Real Clinical Practice (Results of the ANTEY Study)

Aim. To study adherence to treatment with new oral anticoagulants (NOAC) and factors associated with it in patients with non-valvular atrial fibrillation (AF) within the outpatient PROFILE registry.Material and methods. ANTEY study included 201 patients with AF from the PROFILE registry (89.3%): 118 males (58.7%) and 83 females (41.3%), aged 71.1Ѓ}8.7 years. The study consisted of two visits half a year apart (V0, V1) and a phone contact (PC) one year after V0. During V0 all patients were recommended to start therapy with one of the NOACs. Adherence to therapy was assessed during all visits with the use of the original questionnaire – National society of evidence-based pharmacotherapy (NSEPh) adherence scale, 8-item Morisky Medical Adherence Scale (MMAS-8) and direct doctors’ questioning.Results. During V0 111 (55.2%) patients were recommended the use of rivaroxaban; 47 (23.4%) – the use of dabigatran and 43 (21.4%) – the use of apixaban. During V1 based on the results of the NSEPh adherence scale 155 (77.5%) patients were completely adherent (strictly followed doctors’ recommendations), 5 patients were partially adherent (violated doctors’ recommendations), 7 patients were partially non-adherent (stopped taking NOACs), and 33 patients were completely non-adherent (did not start taking NOACs). Out of 197 patients who completed MMAS-8 questionnaire 157 (79.7%) patients were partially adherent to treatment and 40 (20.3%) patients were non-adherent. None of the patients were completely adherent to treatment. According to doctors’ questioning, by the time of the PC 15 patients had not started taking the recommended NOAC – were completely non-adherent (CNA). According to the NSEPh adherence scale, by the time of the PC out of 197 patients (4 patients died) 158 patients were completely adherent to treatment, 6 – partially adherent, 18 – partially non-adherent and 15 – CNA. According to MMAS-8, by the time of the PC 153 (77.7%) patients were partially adherent to treatment, and 44 (22.3%) patients – non-adherent (none of the patients were completely adherent). Out of 15 CNA patients MMAS-8 revealed only 4 (27,6%) during B1, and 6 (40%) during the PC. NSEPh adherence scale revealed all CNA patients. The main reason for refusing to start NOAC therapy was their high price. Recently started use of NOACs was stopped mostly due to adverse effects of therapy (bleeding). The most common factors increasing patients’ adherence to NOACs were previous experience of taking this group of drugs and no history of any adverse effects during therapy.Conclusion. The ANTEY study showed relatively high adherence to NOACs prescribed by doctors of the specialized cardiology department of the scientific center. The most common factors associated with early non-adherence to the new drug were high price and adverse effects of therapy, the latter influenced prolonged adherence as well. Previous experience of taking this group of drugs and no history of any adverse effects during therapy increased adherence to NOACs.

Epistaxis complicating treatment by anti-vitamin K and new oral anticoagulants

ObjectivesTo assess any differences in severity and management of epistaxis when complicating treatment by anti-vitamin K (AVK) or by new oral anticoagulants (NOAC). Materials and methodAll patients admitted to the ENT department of a University Hospital Center for epistaxis under oral anticoagulation therapy between January 2010 and June 2015 were included in a retrospective study. Severity was assessed in terms of management and of hemoglobin level at admission. Two groups were distinguished: treatment by AVK or by NOAC. ResultsOne hundred and thirty-four patients were included: 126 under AVK and 8 under NOAC. There was a significant difference in mean hospital stay: 4.5 days for AVK versus 3.5 days for NOAC (P=0.019; 95% CI [0.1921; 0.8907]). There were no significant differences for the other severity criteria. None of the patients died. ConclusionAdmission rates for epistaxis complicating NOAC therapy was low, and much lower than in case of AVK. Bleeding severity was equivalent with both treatments. NOACs significantly reduce hospital stay. Contrary to the study hypothesis, epistaxis is less serious when complicating NOAC than AVK therapy.

Perioperative management of new oral anticoagulants in patients undergoing elective surgery at a tertiary hospital.

Increasing numbers of patients receiving new oral anticoagulants (NOAC) are undergoing elective surgery. The extent to which perioperative interruption of NOAC therapy and use of bridging heparin are concordant with best evidence is uncertain. To determine: (i) concordance of NOAC and bridging heparin use with guidelines; and (ii) associations between guideline concordance and patient characteristics, surgical factors and perioperative adverse events. Retrospective study of consecutive adult patients undergoing elective surgery at a tertiary hospital between 1 January 2014 and 30 June 2015 and were receiving NOAC for at least 3 months prior to surgery. Concordance of perioperative anticoagulation management with hospital guidelines was rated by two independent researchers according to explicit thrombosis and bleeding risk tables. One hundred and fifty patients of mean (±SD) age 72.0 (±11.6) years were studied; 75% had atrial fibrillation as NOAC indication. Decision to interrupt anticoagulation in 142 patients was rated guideline-concordant in 59 (41.5%) based on low bleeding risk in all cases and high thrombotic risk in one-third. Concordant decisions were associated with past myocardial infarction (P = 0.009), chronic kidney disease (P = 0.05), use of dabigatran (P = 0.06) and major surgery (P < 0.001). Bridging heparin was prescribed in 51 (35.9%) patients and not prescribed in 91 (64.1%), with 64 (45.1%) decisions rated guideline-discordant comprising 27 decisions to prescribe and 37 not to prescribe. Guideline concordant bridging was associated with chronic kidney disease (P = 0.02); discordant bridging with use of dabigatran (P = 0.04), high thrombotic risk (P = 0.004), past ischaemic stroke (P = 0.07). At 30 days, only one adverse event (major bleed) was noted. Considerable discordance exists between guideline recommendations and perioperative NOAC management. Assistive tools are required that better align decision-making with current best practice.

Recent and upcoming randomized trials for left atrial appendage occlusion : Need for a definite assessment of the situation

Atrial fibrillation (AF) is the most common arrhythmia affecting more than 1.6million patients in Germany. Based on demographic developments, an the number is expected to increase. Embolic strokes in AF patients are particularly severe, and individualized new oral anticoagulant (NOAC) therapy reduces the incidence of stroke in these patients by approximately 70%. Besides vitaminK antagonists, the NOACs rivaroxaban, dabigatran, apixaban, and edoxaban have been introduced into clinical practice; however, major bleeding still occurs at arate of 2-3% per year. Moreover, randomized studies and real-life registries suggest that >20% of patients with AF and an indication for anticoagulation cannot tolerate chronic oral anticoagulant therapy. Therefore, an alternative method for stroke prevention in AF patients has been developed, i. e., catheter-based exclusion of the left atrial appendage (LAA), alocation that is prone for thrombus formation in these patients. The randomized trials of catheter-based LAA occlusion have compared this interventional therapy with vitaminK antagonists. In the future, however, LAA exclusion needs to be compared with NOAC therapy. Moreover, percutaneous LAA exclusion in clinical practice is mostly offered to patients ineligible for long-term oral anticoagulation or with high bleeding risk. However, no controlled, randomized trial data exist for this patient population. These data are needed for appropriate clinical judgment and optimal clinical management. Ongoing studies and scientific questions that are important to define the future for catheter-based LAA closure are discussed in this review.

How important it is for therapy adherence to be once a day?

New oral anticoagulants (NOACs) or non-vitamin K antagonists (VKAs) do not possess the numerous negative properties of VKAs in the therapy of atrial fibrillation patients. NOACs have a more rapid onset of action, are less dependent on interactions, food intake, age and body weight, and there are fewer gene polymorphisms. The large Phase III trials have shown that all NOACs are not inferior to VKA therapy. Nevertheless, these results are certainly based on the adherence and persistence to NOAC therapy. A once-a-day strategy has been shown to increase the adherence to therapy. Therefore, this review provides an overview over adherence to NOAC therapy and tries to assess the impact of once-a-day treatment regiments on treatment adherence in anticoagulated patients with atrial fibrillation.

Evaluation of the vascular protective effects of new oral anticoagulants in high-risk patients with atrial fibrillation (PREFER-AF): study protocol for a randomized controlled trial.

BackgroundAtrial fibrillation (AF) is known to be associated with several pathophysiological mechanisms including endothelial dysfunction of the heart and arterial vessels. Recent evidence suggests that new oral anticoagulant (NOAC) treatment may improve endothelial function and the inflammatory process involved in atherosclerosis in AF patients. This study is designed to determine the efficacy of NOAC therapy in the prevention of endothelial dysfunction and the progression of atherosclerosis of AF subjects.Method/designAF patients with a CHA2DS2-VASc score >2 and no previous history of overt coronary disease, severe peripheral arterial disease (PAD) or major stroke will be registered and randomly assigned either to the NOAC group (dabigatran or rivaroxaban) or the warfarin group in this prospective, randomized, 2-year follow-up study. Reactive hyperemia peripheral arterial tonometry (RH-PAT) measurements reflecting endothelial function will be conducted using the Endo-PAT2000 device. Left and right carotid intima-media thickness (IMT) will be measured at baseline, 12 months, and 24 months. The primary endpoint is defined as change in Reactive Hyperemia Index (RHI) at 12 months. Secondary endpoints included changes in the right and left maximum IMT of the common carotid artery (CCA) and internal carotid artery (ICA), the mean IMT of the CCA and ICA at 24 months, and 24-month cardiovascular events including cardiac death, stroke, acute myocardial infarction (AMI), overall cause of death, withdrawal of drug, or bleeding events.DiscussionThis is the first study to evaluate the efficacy of NOAC therapy for the prevention of endothelial dysfunction and progression of atherosclerosis in AF subjects. These findings are expected to expand the knowledge of NOAC pleotropic action in AF patients.Trial registrationClinicalTrials.gov: NCT02544932, registered on 7 September 2015.

New oral anticoagulants: appropriateness of prescribing in real-world setting.

The new oral anticoagulants (NOAC) have been extensively studied in the clinical trial setting; however, concerns remain about the safety of prescribing in the elderly and patients with renal impairment. The aim of this study was to assess the appropriateness of NOAC prescribing in a real-world setting in terms of patient selection and to compare patient demographics to those included in pivotal clinical trials. One hundred and seventy-six patients from three tertiary university teaching hospitals were identified over 3 months in 2014. Median age of the cohort was 74 years (interquartile range: 61-81 years), with a range of 23-96 years. Overall, 34% of the study population were prescribed a NOAC inappropriately. Of these, treatment was contraindicated in 40%, predominantly due to severe renal impairment, 22% were prescribed an excessively high dose, while 38% were under dosed. Although community-initiated patients had poorer renal function (glomerular filtration rate 91.7 ± 55.7 vs 69.3 ± 38.9, P = 0.024), appropriateness of prescription was no different compared to hospital-initiated patients (78% during admission cf. 61% prior, P = 0.061). Appropriate prescribing was better in patients with venous thromboembolism compared to AF (85% appropriate cf. 60%, P = 0.021). Our findings imply that there remains considerable uncertainty about appropriate prescribing and dosing of NOAC, particularly in patients with impaired renal function. We recommend judicious prescribing and regular monitoring of renal function in patients at high risk of complications from NOAC therapy.

Tratamentul cu anticoagulante orale noi în practica medicului de familie

Vitamin K antagonists represented for more than 50 years the only oral anticoagulant treatment option, though encumbered by numerous food and drug interactions, with direct impact on the safety and efficacy of this treatment. The frequent complications of anticoagulant treatment with vitamin K antagonists led to the need for the emergence of new oral anticoagulants (NOAC). The main NOACs used today are dabigatran, rivaroxaban and apixaban. NOAC have a number of advantages over antivitamin K anticoagulants: fewer drug interactions, no food interactions, rapid onset of the anticoagulant action, rapid clearance, no need for INR monitoring. NOAC therapy must be individualized according to patient age, comorbidities and medical history, renal function, concomitant medications. Given that clinical experience with NOAC is still limited in practice, physicians (including family physicians) must monitor these patients and need to pay attention and report any side effects.

Transesophageal echocardiograpy in patients with persistent atrial fibrillation undergoing electrical cardioversion on new oral anticoagulants: A multi center registry

Increased risk of thrombo-embolism following cardioversion foratrial fibrillation (AF) is well recognized. Therefore, anticoagulation isconsidered mandatory before elective cardioversion for AF of N48 h orAF of unknown duration. Vitamin K antagonists (VKAs) (INR 2.0 to3.0) are recommended for at least 3 weeks prior to and 4 weeks aftercardioversion, regardless of the CHA2DS2-VASc score and the method(electrical or pharmacological) used to restore sinus rhythm [1,2].Therisk of thromboembolic events is high (up to 7%) if anticoagulation isinadequate, and is reduced to less than 1% if adequate anticoagulationis achieved [3]. Recently, new oral anticoagulants (NOACs) have beenintroduced intheclinical practiceandsuggestedalso inpatientsunder-going electrical cardioversion for AF. In this context compliance andadherence to treatment are crucial, as these drugs have a relativelyshort half-life. In fact patients missing more than one drug assumptioncannotbeconsideredunderanadequatetherapeuticregimen.Moreover,differently from VKA treatment, that can be followed through INRmeasurements,there are no effective hemoreological tests to assessther-apeutic anticoagulation. One way to assess the ef ficacy of anticoagulationtherapy is the direct search for left atrial thrombus by means oftransesophageal echocardiography (TEE). The aim of our study was toevaluate the incidence of left atrial (LA) thrombus in patients referredfor electrical cardioversion, while on treatment with NOACs, using apre-procedural TEE.Between January 2014 and December 2014 we collected the TEEdata of 219 consecutive patients with persistent AF referred to sevenItalian centers for elective electrical cardioversion, while on NOACs forat least 3 weeks before electrical cardioversion. This study followedtheprinciplesoutlinedinthelatestupdateoftheDeclarationofHelsinkiand all patients signed informed consent. This study was approved byour Institutional Review Boards. Main exclusion criteria were a historyof thromboembolic events, a history of LA thrombus diagnosed byTEE, a TEE procedure performed in the 21 days before starting NOACtherapy, and the need for anticoagulation other than AF. TEE wasperformed with a 5–7-MHz multiplane transducer connected to anultrasoundsystem.Multiplestandardtomographicplaneswereimaged.TheLAappendagepeakflowvelocity,presenceofthrombiintheLA,andseverityofspontaneousechocontrastintheLAweredetermined.Atrialcavityorappendagethrombiwereconsideredtobepresentwhenwell-circumscribed, echodense, intracavitary masses that were acousticallydistinct from the underlying endocardium and pectinate muscles wereidentified.The clinical characteristics of the study population are summarizedin Table 1. The mean duration of AF was 6.2 ± 4.3 months, and themean duration of NOAC therapy was 4.1 ± 3 months. NOACs usedwere dabigatran (86 patients, 39%), rivaroxaban (61 patients, 28%),and apixaban (73 patients, 33%). The daily dabigratan dose was220mgin21patients,and300mgin65patients;thedailyrivaroxabandose was 15 mg in 2 patients, and 20 mg in 59 patients; the dailyapixaban dose was 5 mg in 1 patient, and 10 mg in 72 patients. The

Dynamics of vitamin K antagonist and new oral anticoagulants use in atrial fibrillation: a Danish drug utilization study

Detailed data on real-life utilization of vitamin K antagonists (VKAs) and new oral anticoagulants (NOACs) in atrial fibrillation are sparse. To describe the dynamics of VKA and NOAC use: that is, (i) how patients moved in and out of, as well as between, use of VKAs and NOACs; (ii) how patients adhered to treatment; and (iii) which type of prescriber initiated, maintained, and changed treatment with VKAs and NOACs. We conducted a drug utilization study in the region of southern Denmark (population 1.2 million) using prescription data. We included all subjects using VKAs or NOACs during the period of August 22, 2011, through June 30, 2013, restricted to subjects with a diagnosis of atrial fibrillation. We identified 20,911 subjects, of whom 20,769 and 1639 used VKAs and NOACs, respectively. The number of VKA users was stable at ~ 14,000 subjects during the study period, whereas the number of NOAC users increased to 903. The majority of NOAC users had previously used VKAs (n = 974), whereas 389 anticoagulant-naïve users initiated NOAC therapy. Among the latter, 51.2% had changed to VKAs within 6 months. 57.3% of VKA users were initiated by a hospital physician, whereas maintenance treatment was predominantly handled by the patient's general practitioner (97.6%). Switches from NOAC to VKA were initiated by a general practitioner in 69.2% of the cases. For users of NOACs, these numbers were 73.5%, 94.0%, and 63.3%. A large proportion of NOAC users switch to a VKA within a short time frame. The reasons for this are not clear.

Heparin bridging in peri-procedural management of new oral anticoagulant: a bridge too far?

This editorial refers to ‘Peri-interventional management of novel oral anticoagulants in daily care: results from the prospective Dresden NOAC registry’[‡][1], by J. Beyer-Westendorf et al. , on page 1888. The new oral anticoagulants (NOACs) are attractive alternatives to vitamin K antagonists (VKAs) for patients requiring long-term anticoagulation. NOACs are at least as effective and safe as warfarin while allowing convenient fixed dosing regimens.1,2 Moreover, due to their rapid onset and offset of action,3 NOACs have the potential to simplify the peri-procedural management of patients requiring interruption of anticoagulant treatment for elective interventions. Beyer-Westendorf and colleagues now report thrombotic and bleeding outcomes during the first 30 days after an elective procedure from a prospective registry of 2179 patients receiving long-term NOAC therapy for atrial fibrillation (81%), venous thrombo-embolism (17%), or other indications (2%).4 During an 18-month period, 595 patients underwent a total of 863 elective procedures. Most patients were taking rivaroxaban (76%) or dabigatran (23.5%), and only a minority (0.5%) was taking apixaban. Patients who underwent procedures without interruption of NOAC therapy did not experience major bleeding and had a non-major clinically relevant bleed rate of < 5%. Patients who underwent a procedure with interruption of NOAC therapy and who received bridging anticoagulation [40% of patients; most commonly with low molecular weight heparin (LMWH)] had similar rates of thrombotic events compared with those who did not receive bridging (1.6% vs. … [1]: #fn-3

THE ASSESSMENT OF COMPLIANCE TO THE USE OF NEW ORAL ANTICOAGULANTS IN PATIENTS WITH ATRIAL FIBRILLATION ACCORDING TO THE PROFILE REGISTER

Aim. To study in the PROFILE register the rate of new oral anticoagulants (NOAC) taking in patients with atrial fibrillation (AF) and to identify the factors influencing it. Material and methods. Patients with AF who applied to the Cardiology Center in 2013-2014 (n=111) were included into the study. The oral anticoagulants (OAC) were recommended to patients at the reference visit (n=97). Inquiry in questionnaire format was performed to assess the compliance to recommended therapy at the follow-up visit. Patients were divided into two groups according to taking/not-taking NOAC. Analysis of the facts that influence the compliance to NOAC therapy was performed. Results. At the reference visit 70 patients desired to receive NOAC. At the follow-up visit 29 (41.4%) patients refused to take NOAC. Leading causes of NOAC refusal were satisfactory with warfarin (32.6%), the high price of these drugs (23.9%), the description of adverse reactions in the patient information leaflet for medicines (15.2%), and withdrawal by physician in outpatient clinic/hospital (8.7%). Preferential provision of medicines and warfarin therapy at the time of reference visit had a negative impact on the taking of NOAC. Patients taking NOAC were more aware of the possible outcomes of their illness, the possible side effects of OAC and were more familiar with patient information leaflet for medicines. Conclusion. The study assessed NOAC taking rate and the factors influencing patients' compliance to NOAC therapy.

How to manage new oral anticoagulants in case of surgery

When a patient receiving new oral anticoagulants (NOACs) requires an invasive procedure, the consequences of bleeding if anticoagulation is continued and the risk of thrombosis if it is omitted need to be carefully considered. In addition to the bleeding risk of the procedure, it is of paramount importance to evaluate the renal function, especially for dabigatran that is eliminated predominantly via the renal pathway. NOAC therapy should be stopped for at least 24 h before the intervention, and a longer interruption should be considered in cases of high bleeding risk procedures and/or renal failure. A base-line assessment of coagulation should be performed and intervention should be postponed (if possible) if high levels of anticoagulation parameters are found. In the post-surgical period, if oral anticoagulant therapy cannot be re-started, patients should temporarily receive low molecular weight heparins and re-start NOACs as soon as possible.