-
1.
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
-
-
Free full text
-
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].
-
2.
Rivaroxaban compared with standard anticoagulants for the treatment of acute venous thromboembolism in children: a randomised, controlled, phase 3 trial.
Male, C, Lensing, AWA, Palumbo, JS, Kumar, R, Nurmeev, I, Hege, K, Bonnet, D, Connor, P, Hooimeijer, HL, Torres, M, et al
The Lancet. Haematology. 2020;(1):e18-e27
-
-
Free full text
-
Abstract
BACKGROUND Treatment of venous thromboembolism in children is based on data obtained in adults with little direct documentation of its efficacy and safety in children. The aim of our study was to compare the efficacy and safety of rivaroxaban versus standard anticoagulants in children with venous thromboembolism. METHODS In a multicentre, parallel-group, open-label, randomised study, children (aged 0-17 years) attending 107 paediatric hospitals in 28 countries with documented acute venous thromboembolism who had started heparinisation were assigned (2:1) to bodyweight-adjusted rivaroxaban (tablets or suspension) in a 20-mg equivalent dose or standard anticoagulants (heparin or switched to vitamin K antagonist). Randomisation was stratified by age and venous thromboembolism site. The main treatment period was 3 months (1 month in children <2 years of age with catheter-related venous thromboembolism). The primary efficacy outcome, symptomatic recurrent venous thromboembolism (assessed by intention-to-treat), and the principal safety outcome, major or clinically relevant non-major bleeding (assessed in participants who received ≥1 dose), were centrally assessed by investigators who were unaware of treatment assignment. Repeat imaging was obtained at the end of the main treatment period and compared with baseline imaging tests. This trial is registered with ClinicalTrials.gov, number NCT02234843 and has been completed. FINDINGS From Nov 14, 2014, to Sept 28, 2018, 500 (96%) of the 520 children screened for eligibility were enrolled. After a median follow-up of 91 days (IQR 87-95) in children who had a study treatment period of 3 months (n=463) and 31 days (IQR 29-35) in children who had a study treatment period of 1 month (n=37), symptomatic recurrent venous thromboembolism occurred in four (1%) of 335 children receiving rivaroxaban and five (3%) of 165 receiving standard anticoagulants (hazard ratio [HR] 0·40, 95% CI 0·11-1·41). Repeat imaging showed an improved effect of rivaroxaban on thrombotic burden as compared with standard anticoagulants (p=0·012). Major or clinically relevant non-major bleeding in participants who received ≥1 dose occurred in ten (3%) of 329 children (all non-major) receiving rivaroxaban and in three (2%) of 162 children (two major and one non-major) receiving standard anticoagulants (HR 1·58, 95% CI 0·51-6·27). Absolute and relative efficacy and safety estimates of rivaroxaban versus standard anticoagulation estimates were similar to those in rivaroxaban studies in adults. There were no treatment-related deaths. INTERPRETATION In children with acute venous thromboembolism, treatment with rivaroxaban resulted in a similarly low recurrence risk and reduced thrombotic burden without increased bleeding, as compared with standard anticoagulants. FUNDING Bayer AG and Janssen Research & Development.
-
3.
XALIA-LEA: An observational study of venous thromboembolism treatment with rivaroxaban and standard anticoagulation in the Asia-Pacific, Eastern Europe, the Middle East, Africa and Latin America.
Kreutz, R, Mantovani, LG, Haas, S, Monje, D, Schneider, J, Bugge, JP, Gebel, M, Tamm, M, Ageno, W, Turpie, AGG
Thrombosis research. 2019;:125-132
Abstract
INTRODUCTION The prospective, non-interventional XALIA study investigated the safety and effectiveness of rivaroxaban and standard anticoagulation for the treatment of deep vein thrombosis (DVT). XALIA-LEA was conducted in regions not included in XALIA (Latin America, Eastern Europe, the Middle East, Africa, and the Asia-Pacific), and enrolled patients with isolated pulmonary embolism (PE). MATERIALS AND METHODS Adult patients with acute venous thromboembolism (VTE) indicated for ≥3 months' anticoagulant treatment were eligible; treatment strategies were at the physician's discretion. Patients receiving rivaroxaban or standard anticoagulation (unfractionated or low-molecular weight heparin/fondaparinux alone or overlapping with and followed by a vitamin K antagonist [VKA]) were included in the safety analysis. "Early switchers" to rivaroxaban (i.e. after receiving heparin/fondaparinux for >2-14 days and/or a VKA for 1-14 days) were not included in the safety analysis set. RESULTS Of the 1972 eligible patients, 1285 received rivaroxaban, 402 received standard anticoagulation, and 285 were early switchers. Most patients who received rivaroxaban were appropriately selected, received the correct dosing schedule, reported few adverse effects. Outcomes were similar to previously published results, with rivaroxaban associated with a low rate of major bleeding (1.6%), recurrent VTE (1.4%) and all-cause mortality (2.3%). Including early switchers, relatively fewer patients with index isolated PE received rivaroxaban (14.4%) versus standard anticoagulation therapy (20.9%). Some regional variations and differences in outcomes by VTE subtype were apparent with standard anticoagulation treatment. CONCLUSION XALIA-LEA reaffirms the safety and effectiveness of rivaroxaban for VTE treatment for countries not included in XALIA.
-
4.
Effectiveness and Safety of Apixaban versus Warfarin as Outpatient Treatment of Venous Thromboembolism in U.S. Clinical Practice.
Weycker, D, Li, X, Wygant, GD, Lee, T, Hamilton, M, Luo, X, Vo, L, Mardekian, J, Pan, X, Burns, L, et al
Thrombosis and haemostasis. 2018;(11):1951-1961
-
-
Free full text
-
Abstract
In the AMPLIFY clinical trial, apixaban was non-inferior to warfarin plus subcutaneous enoxaparin bridge therapy in the treatment of acute venous thromboembolism (VTE) and was associated with significantly less bleeding. This study evaluated their comparative effectiveness and safety in routine clinical practice. A matched-cohort design and data from four U.S. private health care claims databases were employed. Study population comprised patients who initiated outpatient treatment with apixaban versus warfarin (plus parenteral anticoagulant bridge therapy) within 30 days of their initial VTE episode; apixaban and warfarin patients were matched on age, characteristics of VTE episode, study database and propensity score. Major bleeding, clinically relevant non-major (CRNM) bleeding and recurrent VTE during the 180-day (maximum) follow-up period were compared using shared frailty models. During mean follow-up of 143 days among apixaban patients (n = 17,878) and 152 days among warfarin patients (n = 17,878), incidence proportions for apixaban versus warfarin, respectively, were 1.7% versus 2.3% for major bleeding, 7.0% versus 9.4% for CRNM bleeding and 2.3% versus 2.9% for recurrent VTE. In shared frailty models, risks of major bleeding (hazard ratio [HR] = 0.75, 95% confidence interval [CI] = 0.64-0.87), CRNM bleeding (HR = 0.77, 95% CI = 0.71-0.83) and recurrent VTE (HR = 0.80, 95% CI = 0.70-0.91) were lower for apixaban versus warfarin. In this large-scale evaluation of VTE patients receiving outpatient treatment with apixaban or warfarin in U.S. clinical practice, risks of major bleeding, CRNM bleeding and recurrent VTE were significantly lower among patients who received apixaban.
-
5.
Simple citrate anticoagulation protocol for low flux haemodialysis.
Lim, EK, Seow, YT, Chen, SE, Yang, G, Liaw, ME, Isaac, S
BMC nephrology. 2018;(1):16
Abstract
BACKGROUND For patients unable to receive heparin anticoagulation during haemodialysis, saline flushes to reduce circuit clotting are often the norm. Regional citrate anticoagulation (RCA) although effective is not used by many centres including in Singapore. We wanted to demonstrate the superiority and safety of a simple regional citrate anticoagulation regime, compared to saline flushes, for heparin-free low flux haemodialysis. METHODS This is a prospective, open label, cross over study on 25 sequential haemodialysis sessions for inpatients receiving heparin-free haemodialysis. Patients were allocated either to regional citrate anticoagulation or standard heparin free haemodialysis and subsequently cross over to the alternate method. RCA was carried out using a protocol derived from previous studies. Assessment of anticoagulation was performed using visual inspection of clot formation in dialysis circuits and post-filter ionized calcium (iCa2+) using point-of-care Ionized calcium device at stipulated intervals. Intravenous Calcium gluconate replacement was given to patients receiving citrate adjusting the rate according to pre-filter iCa2+. Laboratory analyses of electrolytes were also assessed at the start and end of the RCA sessions. RESULTS There were no clots in the RCA arm, with 79% (n = 19) in the saline flush arm having some clot, including 1 clotted circuit. Post-filter iCa2+ at various time points were within acceptable range. Electrolyte readings in the RCA group were all within normal limits except for 4 cases of total Calcium:iCa2+ ratio > 2.5. CONCLUSION RCA is confirmed to be superior to saline flushes for circuit patency. We have a simple and safe protocol that can be followed for low flux haemodialysis. The study was approved by Singapore National Health Group domain-specific ethnical committee. NHG DSRB reference number 2014/01037. TRIAL REGISTRATION Trial registration number: ISRCTN69952745 (registration date 8/11/17).
-
6.
Rivaroxaban vs Warfarin Sodium in the Ultra-Early Period After Atrial Fibrillation-Related Mild Ischemic Stroke: A Randomized Clinical Trial.
Hong, KS, Kwon, SU, Lee, SH, Lee, JS, Kim, YJ, Song, TJ, Kim, YD, Park, MS, Kim, EG, Cha, JK, et al
JAMA neurology. 2017;(10):1206-1215
-
-
Free full text
-
Abstract
IMPORTANCE In atrial fibrillation (AF)-related acute ischemic stroke, the optimal oral anticoagulation strategy remains unclear. OBJECTIVE To test whether rivaroxaban or warfarin sodium is safer and more effective for preventing early recurrent stroke in patients with AF-related acute ischemic stroke. DESIGN, SETTING, AND PARTICIPANTS A randomized, multicenter, open-label, blinded end point evaluation, comparative phase 2 trial was conducted from April 28, 2014, to December 7, 2015, at 14 academic medical centers in South Korea among patients with mild AF-related stroke within the previous 5 days who were deemed suitable for early anticoagulation. Analysis was performed on a modified intent-to-treat basis. INTERVENTIONS Participants were randomized 1:1 to receive rivaroxaban, 10 mg/d for 5 days followed by 15 or 20 mg/d, or warfarin with a target international normalized ratio of 2.0-3.0, for 4 weeks. MAIN OUTCOMES AND MEASURES The primary end point was the composite of new ischemic lesion or new intracranial hemorrhage seen on results of magnetic resonance imaging at 4 weeks. Primary analysis was performed in patients who received at least 1 dose of study medications and completed follow-up magnetic resonance imaging. Key secondary end points were individual components of the primary end point and hospitalization length. RESULTS Of 195 patients randomized, 183 individuals (76 women and 107 men; mean [SD] age, 70.4 [10.4] years) completed magnetic resonance imaging follow-up and were included in the primary end point analysis. The rivaroxaban group (n = 95) and warfarin group (n = 88) showed no differences in the primary end point (47 [49.5%] vs 48 [54.5%]; relative risk, 0.91; 95% CI, 0.69-1.20; P = .49) or its individual components (new ischemic lesion: 28 [29.5%] vs 31 of 87 [35.6%]; relative risk, 0.83; 95% CI, 0.54-1.26; P = .38; new intracranial hemorrhage: 30 [31.6%] vs 25 of 87 [28.7%]; relative risk, 1.10; 95% CI, 0.70-1.71; P = .68). Each group had 1 clinical ischemic stroke, and all new intracranial hemorrhages were asymptomatic hemorrhagic transformations. Hospitalization length was reduced with rivaroxaban compared with warfarin (median, 4.0 days [interquartile range, 2.0-6.0 days] vs 6.0 days [interquartile range, 4.0-8.0]; P < .001). CONCLUSIONS AND RELEVANCE In mild AF-related acute ischemic stroke, rivaroxaban and warfarin had comparable safety and efficacy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT02042534.
-
7.
Efficacy and safety of left atrial appendage closure with WATCHMAN in patients with or without contraindication to oral anticoagulation: 1-Year follow-up outcome data of the EWOLUTION trial.
Boersma, LV, Ince, H, Kische, S, Pokushalov, E, Schmitz, T, Schmidt, B, Gori, T, Meincke, F, Protopopov, AV, Betts, T, et al
Heart rhythm. 2017;(9):1302-1308
Abstract
BACKGROUND Left atrial appendage (LAA) occlusion with WATCHMAN has emerged as viable alternative to vitamin K antagonists in randomized controlled trials. OBJECTIVE EWOLUTION was designed to provide data in routine practice from a prospective multicenter registry. METHODS A total of 1025 patients scheduled for a WATCHMAN implant were prospectively and sequentially enrolled at 47 centers. Indication for LAA closure was based on European Society of Cardiology guidelines. Follow-up and transesophageal echocardiography (TEE) were performed per local practice. RESULTS The baseline CHA2DS2-VASc score was 4.5 ± 1.6; the mean age was 73.4 ± 9 years; previous transient ischemic attack/ischemic stroke was present in 312 (30.5%), 155 (15.1%) had previous hemorrhagic stroke, and 320 (31.3%) had a history of major bleeding; and 750 (73%) were deemed unsuitable for oral anticoagulation therapy. WATCHMAN implant succeeded in 1005 (98.5%) of patients, without leaks >5 mm in 1002 (99.7%) with at least 1 TEE follow-up in 875 patients (87%). Antiplatelet therapy was used in 784 (83%), while vitamin K antagonists were used in only 75 (8%). At 1 year, mortality was 98 (9.8%), reflecting the advanced age and comorbidities in this population. Device thrombus was observed in 28 patients at routine TEE (3.7%) and was not correlated with the drug regimen (P = .14). Ischemic stroke rate was 1.1% (relative risk 84% vs estimated historical data); the major bleeding rate was 2.6% and was predominantly (2.3%) nonprocedure/device related. CONCLUSION LAA closure with the WATCHMAN device has a high implant and sealing success. This method of stroke risk reduction appears to be safe and effective with an ischemic stroke rate as low as 1.1%, even though 73% of patients had a contraindication to and were not using oral anticoagulation.
-
8.
Coagulation Testing in Acute Ischemic Stroke Patients Taking Non-Vitamin K Antagonist Oral Anticoagulants.
Purrucker, JC, Haas, K, Rizos, T, Khan, S, Poli, S, Kraft, P, Kleinschnitz, C, Dziewas, R, Binder, A, Palm, F, et al
Stroke. 2017;(1):152-158
-
-
Free full text
-
Abstract
BACKGROUND AND PURPOSE In patients who present with acute ischemic stroke while on treatment with non-vitamin K antagonist oral anticoagulants (NOACs), coagulation testing is necessary to confirm the eligibility for thrombolytic therapy. We evaluated the current use of coagulation testing in routine clinical practice in patients who were on NOAC treatment at the time of acute ischemic stroke. METHODS Prospective multicenter observational RASUNOA registry (Registry of Acute Stroke Under New Oral Anticoagulants; February 2012-2015). Results of locally performed nonspecific (international normalized ratio, activated partial thromboplastin time, and thrombin time) and specific (antifactor Xa tests, hemoclot assay) coagulation tests were documented. The implications of test results for thrombolysis decision-making were explored. RESULTS In the 290 patients enrolled, nonspecific coagulation tests were performed in ≥95% and specific coagulation tests in 26.9% of patients. Normal values of activated partial thromboplastin time and international normalized ratio did not reliably rule out peak drug levels at the time of the diagnostic tests (false-negative rates 11%-44% [95% confidence interval 1%-69%]). Twelve percent of patients apparently failed to take the prescribed NOAC prior to the acute event. Only 5.7% (9/159) of patients in the 4.5-hour time window received thrombolysis, and NOAC treatment was documented as main reason for not administering thrombolysis in 52.7% (79/150) of patients. CONCLUSIONS NOAC treatment currently poses a significant barrier to thrombolysis in ischemic stroke. Because nonspecific coagulation test results within normal range have a high false-negative rate for detection of relevant drug concentrations, rapid drug-specific tests for thrombolysis decision-making should be established. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01850797.
-
9.
Effects of non-vitamin K antagonist oral anticoagulants on fibrin clot and whole blood clot formation, integrity and thrombolysis in patients with atrial fibrillation.
Lau, YC, Xiong, Q, Shantsila, E, Lip, GY, Blann, AD
Journal of thrombosis and thrombolysis. 2016;(4):535-44
-
-
Free full text
-
Abstract
Non-vitamin K antagonist oral anticoagulants (NOACs) are replacing warfarin and heparins in several clinical situations. With varying modes of action, the effects of NOACs on thrombus formation, integrity, and lysis is unknown. To determine whether two techniques of thrombelastography (TEG) and a micro-plate assay (MPA) provide novel data on thrombus formation, integrity and lysis in those taking a NOACs compared to warfarin and a control group taking aspirin. We assessed thrombogenesis, clot integrity and fibrinolysis in blood (TEG) and plasma (MPA) from 182 atrial fibrillation patients-50 on aspirin, 50 on warfarin, and 82 on a NOAC (17 apixaban, 19 dabigatran and 46 rivaroxaban). Eleven of 16 TEG indices and 4 of 5 MPA indices differed (p ≤ 0.01) between those on aspirin, warfarin or a NOAC. Three TEG indices and 4 MPA indices differed (p < 0.01) between the NOACs. Time to initiation of clot formation was most rapid on apixaban, then rivaroxaban and slowest on dabigatran. The rate of clot formation was most rapid on dabigatran, then apixaban, and slowest on rivaroxaban. Clot density was greatest on rivaroxaban, then apixaban, but weakest on dabigatran. The rate of clot dissolution was most rapid in apixaban, then dabigatran, and slowest on rivaroxaban. The TEG and MPA identify major differences in thrombogenesis and fibrinolysis in different NOACs. These techniques may have value in investigating the effects of these drugs on haemostasis in a clinical setting, and in identifying those in need of targeted therapy.
-
10.
An epidemiological study to evaluate the use of vitamin K antagonists and new oral anticoagulants among non-valvular atrial fibrillation patients in Turkey- AFTER-2 study design.
Ertaş, F, Kaya, H, Yıldız, A, Davutoğlu, V, Kiriş, A, Dinç, L, Kafes, H, Avcı, A, Calapkorur, B, Ertaş, G, et al
Turk Kardiyoloji Dernegi arsivi : Turk Kardiyoloji Derneginin yayin organidir. 2015;(2):169-77
Abstract
OBJECTIVES Atrial fibrillation (AF) is one of the most common causes of preventable ischemic stroke and is related to increased cardiovascular morbidity and mortality. There is a lack of data in Turkey on the use of new oral anticoagulants (NOACs), and time in therapeutic INR range (TTR) in vitamin K antagonist users and AF management modality. In this multi-center trial, we aimed to analyze, follow and evaluate the epidemiological data in non-valvular AF patients. STUDY DESIGN Four thousand one hundred consecutive adult patients from 42 centers with at least one AF attack identified on electrocardiography will be included in the study. Patients with rheumatic mitral valve stenosis and prosthetic valve disease will be excluded from the study. At the end of one year, the patients will be evaluated in terms of major cardiac end points (death, transient ischemic attack, stroke, systemic thromboembolism, major bleeding and hospitalization). RESULTS First results are expected in June 2015. Data about major cardiovascular end-points will be available in January 2016. CONCLUSION The rates and kind of oral anticoagulant use, TTR in vitamin K antagonist users and main management modality applied in non-valvular AF patients will be determined by AFTER-2 study. In addition, the rate of major adverse events (MACEs) and the independent predictors of these MACEs will be detected (AFTER-2 Study ClinicalTrials.gov number, NCT02354456.).