Use Of Non-vitamin K Antagonist Oral Anticoagulants In Patients Research Articles

Non-vitamin K antagonist oral anticoagulants in patients with valvular heart disease.

The non-vitamin K antagonist oral anticoagulants (NOACs) dabigatran, rivaroxaban, apixaban, and edoxaban have transformed the management of atrial fibrillation (AF), but are only approved by regulatory authorities for stroke prophylaxis in patients with so-called “non-valvular AF.” This terminology has spawned confusion about which patients with valvular heart disease benefit from NOACs and which should be treated with vitamin K antagonists (VKAs) instead. Patients with valvular heart disease other than mechanical prosthetic valves or severe mitral stenosis (including those with bioprosthetic valves) were included in pivotal trials demonstrating the benefit of NOACs over VKAs, and consensus guidelines recommend NOACs over VKAs in these patients. Subsequent devoted randomized controlled trials in patients with AF and bioprosthetic valves, including transcatheter valves, have confirmed the safety of NOACs in this population. In patients with rheumatic mitral stenosis, observational studies indicate that NOACs may be safe and effective, but randomized controlled trials are ongoing. By contrast, a randomized controlled trial showed that dabigatran is harmful in patients with mechanical prosthetic mitral valves; however, these data may not extrapolate to patients with mechanical valve prostheses in other locations or to other NOACs, and randomized controlled trials are ongoing. In this review, we discuss these data in greater depth, and make recommendations for the use of NOACs in patients with valvular heart disease.

Non-vitamin K antagonist oral anticoagulants in atrial fibrillation patients with advanced chronic kidney and liver diseases.

Advanced chronic kidney disease (CKD) or chronic liver disease (CLD) is frequent in patients with atrial fibrillation (AF) because of their common risk factors. Chronic kidney disease and CLD superimposed on AF are associated with increased risks of thrombosis and bleeding, which further complicates the use of oral anticoagulants (OACs). Because currently approved non-vitamin K antagonist oral anticoagulants (NOACs) undergo certain degrees of metabolism and clearance in the liver and kidney, increased exposure to medications and risk of bleeding are major concerns with the use of NOACs in patients with advanced CKD and CLD. Besides, these patients were mostly excluded from landmark trials of NOACs and related cohort studies are also limited. Therefore, the optimal strategy for the use of NOACs in this population remains unclear. This review would go through current evidence regarding the safety and efficacy of NOACs in AF patients with advanced CKD and CLD and provide a comprehensive discussion for clinical practices.

Oral Anticoagulant Treatment in Patients with Atrial Fibrillation and Chronic Kidney Disease.

Over the past few decades, a series of innovative medicines have been developed in order to optimize anticoagulation therapy for atrial fibrillation (AF). As a result, a number of nonvitamin K antagonist oral anticoagulants (NOAC) that directly target the enzymatic activity of factor II and factor Xa have been successfully licensed providing a more predictable effect and better safety profile compared to conventional anticoagulants (heparins and vitamin K antagonists (VKAs)). However, comparative efficacy and safety data is limited in patients with advanced chronic kidney disease (i.e., CKD stage 4/5 and end stage renal disease) because patients with estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 were actively excluded from landmark trials, thus representing a major clinical limitation for the currently available agents. However, the renal function of AF patients can be altered over time. On the other hand, patients with CKD have an increased risk of developing AF. This review article will provide an overview of current concepts and recent evidence guiding the clinical use of NOACs in patients with CKD requiring chronic anticoagulation, and the associated risks and benefits of treatment in this specific patient population.

Clinical Performance of Nonvitamin K Antagonist Oral Anticoagulants in Real-World Obese Patients with Atrial Fibrillation.

The prevalence of both atrial fibrillation (AF) and obesity has steadily increased. Nonvitamin K antagonist oral anticoagulants (NOACs) have been shown to be more effective and safer than vitamin K antagonists (VKAs) for long-term stroke prevention in patients with nonvalvular AF. There are still limited data in the literature regarding performance of NOACs in obese patients with AF in the "real world." The aim of our study was to compare the safety and effectiveness of NOACs versus well-controlled VKA therapy in obese AF patients in a "real-world" setting. Here, we have considered patients with AF and obesity (body mass index [BMI] > 30 kg/m2) on NOAC or VKA therapy included in the multicenter Atrial Fibrillation Research Database (NCT03760874). The occurrence of major bleedings (MBs) and thromboembolic events (composite of ischemic stroke, transient ischemic attack, and systemic embolism) was respectively considered primary safety and effectiveness outcomes. We identified 1,047 AF patients with obesity who received NOAC (n = 272) or VKA (n = 775) treatment. After propensity score matching analysis, 248 NOAC and 496 VKA recipients with similar clinical characteristics, including BMI (34.8 ± 3.4 in NOAC vs. 35.1 ± 3.8 in the VKA group; p = 0.50), were evaluated. The mean follow-up was 39 ± 7 months. The incidence rate of thromboembolic events was 1.10 per 100 person-years (0.67 in NOAC vs. 1.28 in the VKA group; hazard ratio [HR]: 0.52; 95% confidence interval [CI]: 0.22-1.22; p = 0.19). The incidence rate of MB was 1.9 per 100 person-years (1.1 in NOAC vs. 2.28 in the VKA group; HR: 0.46; 95% CI: 0.24-0.88; p = 0.04). The incidence rate of intracranial hemorrhage was 0.4 per 100 person-years (0.27 in NOAC vs. 0.47 in the VKA group; HR: 0.57; 95% CI: 0.12-2.73; p = 0.48). A positive net clinical benefit (NCB) of NOACs over VKAs was found (+0.91). Presence of anemia (HR: 1.75; p = 0.003) and concomitant use of antiplatelet drugs (HR: 2.41; p = 0.001) were found to be independent predictors of MB; moreover, age (HR: 1.65; p = 0.003) was an independent predictor of thromboembolic events. Our data support the hypothesis of safe and effective use of NOACs in patients with AF and obesity, justified by a statistically significant lower incidence of MB and a favorable NCB over VKAs.

P471Experience with the use of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation and a high risk of hemorrhagic complications

Abstract Background. The use of NOACs in patients with chronic lymphocytic leukemia (CLL) is a difficult task due to the tendency to hemorrhage in these patients associated with CLL. The use of targeted ibrutinib (Ib) therapy in the treatment of CLL patients increases the risk of bleeding due to thrombocytopathy. A feature of targeted Ib therapy is the need for daily and lifelong use. One of the cardiotoxic effects of Ib is the development of atrial fibrillation (AF). Some patients receiving Ib have a history of AF. Warfarin is contraindicated in patients taking Ib, so all patients received NOACs. Purpose. To evaluate the possibility of using NOACs in CLL patients receiving Ib, taking into account the frequency and severity of hemorrhagic manifestations, the need to cancel, reduce the dose and replace with another NOACs. Methods. We examined and observed the dynamics of 224 patients with CLL receiving Ib from 5 to 56 months at a dose of 420 mg per day as 1, 2, 3, and 4 lines of CLL therapy. Patients with CLL aged 32 to 91 years (66.0 (59.0-72.0) years) were Included, of whom 82 are women aged 39 to 83 years (64.0 (54.0-71.0 ) years) and 142 men aged 32 to 91 years (66.0 (60.0-72.0) years). All hemorrhagic manifestations in patients receiving Ib and NOACs were evaluated, taking into account the glomerular filtration rate and platelet count. Results. AF were revealed in 51 patients with CLL receiving Ib. AF was registered in 32 patients during the treatment with Ib, in 19 patients AF was before prescribing of Ib. The need for NOACs because of AF arose in 38 patients with CLL who were prescribed rivaroxaban (n = 11), dabigatran (n = 6), apixaban (n = 21). Hemorrhages were observed in 88.2% of patients receiving NOACs and Ib, represented by hematomas (n = 32), petechiae (n = 4), nosebleeds (n = 6), gingival bleeding (n = 7), hemorrhage in the anterior chamber of the eye (n = 1), hemorrhage in the sclera of the eye (n = 3) and macrohematuria (n = 4). A combination of several hemorrhagic manifestations (combined hemorrhages) was observed in 40.7% of CLL patients receiving NOACs. 10 patients were transferred to the minimum dose of apixaban 2.5 mg twice a day due to the development of recurring nosebleeds (n = 5), macrohematuria (n = 3), large, recurring hematomas with localization on the neck and face (n = 1 ), hemorrhages in the anterior chamber of the eye (n = 1). Cancellation of NOACs in 1 patient was associated with recurrent macrohematuria. Rivaroxaban 20 mg per day was canceled in 6 patients due to the development of persistent thrombocytopenia of less than 50 × 109/L. Conclusions. There were no life-threatening hemorrhages. The main reason for the withdrawal of NOACs was persistent thrombocytopenia. Due to hemorrhagic complication, NOACs was canceled only in 1 patient, 10 patients (26.3%) required a transfer to the minimum dose of apixaban. The arising hemorrhages did not require hospitalization of patients.

Recommendations on the Use of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation (Based on 2018 European Heart Rhythm Association Practical Guide)

Non-vitamin K antagonist oral anticoagulants (NOACs) - direct oral anticoagulants - are getting the ever-broadening use in clinical practice. However, many problems related to optimal use of NOACs in specific clinical situations remain unresolved. European Heart Rhythm Association in April 2018 issued the renovated recommendations on the use of NOACs in patients with atrial fibrillation. The authors of recommendations presented some specific clinical variants for which they formulated practical advices based on the evidence obtained in randomized clinical trials. They also outlined the indications for use of NOACs, formulated practical start-program and scheme of subsequent follow-up management of patients taking NOACs. Recommendations contain information on pharmacokinetics of NOACs and their interactions with other drugs, consideration of feasibility of NOACs use in patients with chronic renal insufficiency or advanced liver disease. Many other practical problems are covered as well.

Non-vitaminK antagonist oral anticoagulants in patients with an increased risk of bleeding.

SummaryThe non-vitamin K antagonist oral anticoagulants (NOACs) have considerably changed clinical practice and are increasingly being used as an alternative to vitamin K antagonists (VKAs) for 3 main reasons: 1) an improved benefit-risk ratio (in particular lower rates of intracranial bleeding), 2) a more predictable effect without the need for routine monitoring, and 3) fewer food and drug interactions compared with VKAs. Currently, there are four NOACs available: the factor Xa inhibitors apixaban, edoxaban, and rivaroxaban, and the thrombin inhibitor dabigatran. This consensus paper reviews the properties and usage of NOACs in a number of high-risk patient populations, such as patients with chronic kidney disease, patients ≥80 years of age and others and provides guidance for the use of NOACs in patients at risk of bleeding.

Stroke prevention strategies in patients with atrial fibrillation and heart valve abnormalities: perceptions of 'valvular' atrial fibrillation: results of the European Heart Rhythm Association Survey.

The purpose of this European Heart Rhythm Association (EHRA) Survey was to assess the perceptions of 'valvular' atrial fibrillation (AF) and management of AF patients with various heart valve abnormalities in daily clinical practice in European electrophysiology (EP) centres. Questionnaire survey was sent via the Internet to the EHRA-EP Research Network Centres. Of the 52 responding centres, 42 (80.8%) were university hospitals. Choosing the most comprehensive definition of valvular AF, a total of 49 centres (94.2%) encountered a mechanical prosthetic heart valve and significant rheumatic mitral stenosis, 35 centres (67.3%) also considered bioprosthetic valves, and 25 centres (48.1%) included any significant valvular heart disease, requiring surgical repair in the definition of valvular AF. Only three centres (5.8%) would define valvular AF as the presence of any (even mild) valvular abnormality. None of the centres would use non-vitamin K antagonist oral anticoagulants (NOACs) in AF patients with mechanical prosthetic valves, only 5 centres (9.8%) would use NOACs in patients with significant mitral stenosis, 17 centres (32.7%) would consider the use of NOACs in patients with bioprosthetic valves, and 21 centres (41.2%) would use NOACs in patients with a non-recent transcatheter valve replacement/implantation, while 13 centres (25.5%) would never consider the use of NOACs in AF patients with even mild native heart valve abnormality. Our survey showed marked heterogeneity in the definition of valvular AF and thromboprophylactic treatments, with the use of variable NOACs in patients with valvular heart disease other than prosthetic heart valves or significant mitral stenosis, indicating that this term may be misleading and should not be used.

Efficacy and Safety of Non-Vitamin K Antagonist Oral Anticoagulants versus Vitamin K Antagonist Oral Anticoagulants in Patients Undergoing Radiofrequency Catheter Ablation of Atrial Fibrillation: A Meta-Analysis.

BackgroundUse of the non-vitamin K antagonist oral anticoagulants (NOACs) is endorsed by current guidelines for stroke prevention in patients with atrial fibrillation (AF). However efficacy and safety of NOACs in patients undergoing catheter ablation (RFCA) of AF has not been well established yet.ObjectivesTo perform a meta-analysis of all studies comparing NOACs and vitamin K antagonist oral anticoagulants (VKAs) in patients undergoing RFCA.Data SourcesStudies were searched for in PubMed and Google Scholar databases.Study Eligibility CriteriaStudies were considered eligible if: they evaluated the clinical impact of NOACs versus VKAs; they specifically analyzed the use of anticoagulants during periprocedural phase of RFCA; they reported clinical outcome data.Study Appraisal and Synthesis Methods25 studies were selected, including 9881 cases. The summary measure used was the risk ratio (RR) with 95% confidence interval (CI). The random-effects or the fixed effect model were used to synthesize results from the selected studies.ResultsThere was no significant difference in thromboembolic complications (RR 1.39; p=0.13). Bleeding complications were significantly lower in the NOACs-treated arm as compared to VKAs (RR=0.67, p<0.001). Interestingly, a larger number of thromboembolic events was found in the VKAs-treated arm in those studies where VKAs had been interrupted during the periprocedural phase (RR=0.68; p=ns). In this same subgroup a significantly higher incidence of both minor (RR=0.54; p=0.002) and major bleeding (RR=0.41; p=0.01) events was recorded. Conversely, the incidence of thromboembolic events in the VKAs-treated arm was significantly lower in those studies with uninterrupted periprocedural anticoagulation treatment (RR=1.89; p=0.02).LimitationsAs with every meta-analysis, no patients-level data were available.Conclusions and ImplicationsThe use of NOACs in patients undergoing RFCA is safe, given the lower incidence of bleedings observed with NOACs. On the other side, periprocedural interruption of VKAs and bridging with heparin is associated with a higher bleeding rate with no significant benefit on onset of thromboembolic events.