Rivaroxaban In Clinical Practice Research Articles

Clinical profile and outcomes in very elderly patients with atrial fibrillation anticoagulated with rivaroxaban: data from the EMIR study.

To analyze the clinical profile, adequacy of treatment with rivaroxaban and outcomes in octogenarians with atrial fibrillation (AF), taking rivaroxaban in clinical practice. Observational and non-interventional study that included AF adults recruited from 79 Spanish centers, anticoagulated with rivaroxaban ≥ 6 months before being included. Data were analyzed according to age (≥ 80 vs. < 80 years) at baseline. Out of 1433 patients, 453 (31.6%) were octogenarians at baseline. Compared to younger patients, octogenarians had more comorbidities, higher CHA2DS2-VASc (4.5 ± 1.3 vs. 3.0 ± 1.4; P < 0.001) and HAS-BLED scores (2.0 ± 1.0 vs. 1.4 ± 1.0; P < 0.001). Overall, the dose of rivaroxaban was adequately prescribed in 83.4% of patients, but more frequently in the younger population (71.1% vs. 89.1%; P = 0.039). After a mean follow-up of 2.2 ± 0.6 years, annual rates of stroke + systemic embolism + transient ischemic attack, MACE, cardiovascular death and major bleeding were 1.03%, 1.24%, 1.03% and 1.75%, respectively, in octogenarian patients. Except for progressive heart failure death and major bleeding, rates of outcomes in octogenarians were similar compared to younger patients. In octogenarians, the concomitant use of antiplatelet agents and non-severe dementia were independently associated with the development of ischemic stroke, whereas previous coronary revascularization and heart failure with MACE, and higher HAS-BLED score with major bleeding. In clinical practice, around one third of patients taking rivaroxaban are octogenarians. These patients have many comorbidities and a high thromboembolic risk. Despite that, rates of adverse events remain low. Rivaroxaban is adequately prescribed in the majority of octogenarians.

Poor Correlation of Rivaroxaban Concentration with the Routine Coagulation Screening Test in Chinese Patients with Atrial Fibrillation

Aims. The aim of this study is to assess the relationship between rivaroxaban plasma concentration quantified by the gold standard and anticoagulant activities measured by routine coagulation assays in Chinese atrial fibrillation (AF) patients. Whether the normal results of these tests were reliable to rule out clinically relevant rivaroxaban levels at various thresholds was also explored. The effect of clinical drug-drug interactions (DDIs) on the exposure and anticoagulant effect of rivaroxaban were further evaluated. Methods. 116 patients receiving rivaroxaban for the management of nonvalvular AF were recruited. Rivaroxaban concentrations and coagulation tests were measured by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and a blood coagulation analyzer, respectively. Results. The correlation of trough concentration (Ctrough) and prothrombin time (PT) or international normalized ratio (INR) was moderate with Spearman’s correlation coefficient of 0.495 and 0.506, respectively. A normal PT/INR was unable to rule out Ctrough levels of &gt;30 ng/mL and &gt;50 ng/mL, but the negative predictive value reached 100% to exclude Ctrough of &gt;100 ng/mL. Ctrough showed a small correlation with activated partial thromboplastin time (aPTT) (Spearman’s correlation coefficient: 0.241) and no correlation with thrombin time (TT) (Spearman’s correlation coefficient: 0.074). Neither aPTT nor TT accurately predicted Ctrough at any concentration. Peak concentration (Cpeak) did not correlate with any coagulation parameters. The presence of digoxin and febuxostat significantly increased rivaroxaban Ctrough by 2.18 fold and prolonged PT and INR by 44.16% and 43.60%, respectively. Conclusions. Normal routine coagulation assays were insufficient to monitor therapy with rivaroxaban. Poor correlations between rivaroxaban concentration and routine coagulation assays were observed in Chinese AF patients. The use of digoxin/febuxostat alone had no effect on rivaroxaban concentrations; however, combined strong breast cancer resistance protein inhibitor (febuxostat) and P-glycoprotein probe (digoxin) in patients with renal impairment is likely to cause clinically significant DDI with rivaroxaban. More studies are needed to establish routine therapeutic drug monitoring of rivaroxaban in clinical practice.

Rivaroxaban Monotherapy in Patients with Pulmonary Embolism: Off-Label vs. Labeled Therapy.

Background: The use of rivaroxaban in clinical practice often deviates from manufacturer prescribing information. No studies have demonstrated an association between this practice and improved outcomes. Methods: We used the RIETE registry to assess the clinical characteristics of patients with pulmonary embolism (PE) who received off-label rivaroxaban, and to compare their 3-month outcomes with those receiving the labeled therapy. The patients were classified into four subgroups: (1) labeled therapy; (2) delayed start; (3) low doses and (4) both conditions. Results: From May 2013 to May 2022, 2490 patients with PE received rivaroxaban: labeled therapy—1485 (58.6%); delayed start—808 (32.5%); low doses—143 (5.7%); both conditions—54 (2.2%). Patients with a delayed start were more likely to present with syncope, hypotension, raised troponin levels and more severe abnormalities on the echocardiogram than those on labeled therapy. Patients receiving low doses were most likely to have cancer, recent bleeding, anemia, thrombocytopenia or renal insufficiency. During the first 3 months, 3 patients developed PE recurrence, 4 had deep-vein thrombosis, 11 had major bleeding and 16 died. The rates of major bleeding (11 vs. 0; p < 0.001) or death (15 vs. 1; OR: 22.5; 95% CI: 2.97–170.5) were higher in patients receiving off-label rivaroxaban than in those on labeled therapy, with no differences in VTE recurrence (OR: 1.11; 95% CI: 0.25–6.57). Conclusions: In patients with severe PE, the start of rivaroxaban administration was often delayed. In those at increased risk for bleeding, it was often prescribed at low doses. Both subgroups had a worse outcome than those on labeled rivaroxaban.

Thromboembolic and bleeding events with rivaroxaban in clinical practice in Spain: impact of inappropriate doses (the EMIR study).

Aim: To analyze the frequency and variables related to inappropriate rivaroxaban dosage in clinical practice and its impact on outcomes after 2years. Materials & methods: Postauthorization, observational, multicenter study, in which atrial fibrillation patients, treated with rivaroxaban ≥6months were included. Results:A total of1421 patients (74.2±9.7years, CHA2DS2-VASc 3.5±1.6) were included. Overall, 22.9% received rivaroxaban 15mg. The proper dose of rivaroxaban was taken by 83.3% (9.7% underdosed, 7.0% overdosed). Older age and renal insufficiency were associated with inadequate rivaroxaban dosage. There was a trend toward higher all-cause mortality among underdosed patients (adjusted hazard ratio 1.39; 95% CI 0.75-2.58), and more bleedings in overdosed patients (2.29 vs 0.80 events/100 patient-years; p = 0.14). Conclusion: In clinical practice, rivaroxaban is properly dosed in most patients.

Rivaroxaban in atrial fibrillation cardioversion: an update.

Currently, atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, with a prevalence of about 2–3% in the general population, representing a powerful risk factor for stroke and systemic thromboembolism and increased mortality and morbidity. Restoration of sinus rhythm is an important treatment option in AF and has a high success rate, but there is the need for an effective anticoagulation strategy to reduce the risk of embolic events. Anticoagulation with vitamin K antagonists is often associated with failure to achieving effective international normalized ratio. In this setting, recent data have led to extended approval for rivaroxaban in clinical practice, because it is effective and safe in patients with AF undergoing cardioversion, avoiding additional health costs and related time loss, while improving patient satisfaction. The present report provides an overview of the main randomized controlled trial and the main real-life studies, documenting the use of rivaroxaban in patients with non-valvular AF who underwent the cardioversion procedure. Considering that novel non-vitamin K antagonist oral anticoagulants in left atrial appendage thrombi resolution is still unknown in the real-world practice, the main findings on the use of rivaroxaban in this setting are also discussed.

Rivaroxaban: One For All, All For One

For the past 10 years, the introduction of rivaroxaban in clinical practice has produced dramatic changes in lives of patients affected by thrombotic disorders. In this review, we discuss rivaroxaban’s pharmacokinetic properties, focusing on the issues of interactions with other drugs and on the appropriate clinical use of coagulation tests in patients treated with this drug. We also examine the many clinical scenarios in which rivaroxaban was tested. In particular, results of studies on venous thromboembolism (VTE) prevention in orthopaedic surgery, deep vein thrombosis (DVT) and pulmonary embolism (PE) acute and long-term treatment with a focus on cancer patients, stroke prevention in atrial fibrillation (AF) with a special mention for cardioversion and trans-catheter ablation and atherosclerotic cardiovascular disease are presented. Our objective is to provide a summary of the evidence in order for the physician to be able to critically apply this information to patients’ management in everyday clinical practice.

Effectiveness and safety of rivaroxaban in a cohort of 142 patients with nonvalvular atrial fibrillation treated with rivaroxaban for the prevention of stroke.

To evaluate the clinical profile and effectiveness/safety of patients taking rivaroxaban in clinical practice. Retrospective study that included patients with nonvalvular atrial fibrillation treated with rivaroxaban for the prevention of stroke between January 2012 and December 2016 in a tertiary hospital in Spain. A total of 142 patients (median age 78years, 40.1% men, 32.4% creatinine clearance<50ml/min; 96.5% CHA2DS2-VASc≥2; 44.3% HAS-BLED≥3) were included. Only two patients had a thromboembolic event (in both cases ischemic stroke) and three patients had major bleeding (rates of 1.3 and 1.9 events/100 patient years, respectively). Data regarding effectiveness and safety in our cohort were consistent with previous studies, showing that rivaroxaban can be effective and safely used in our setting.

Use of rivaroxaban for the prevention of stroke in patients with nonvalvular atrial fibrillation in Spain.

To analyze the clinical profile and rates of stroke, major bleeding and intracranial hemorrhage of patients with atrial fibrillation (AF) treated with rivaroxaban in clinical practice. Retrospective study of AF patients anticoagulated with rivaroxaban in a Healthcare Area of Valencia, Spain. Patients started treatment with rivaroxaban from July 2012 to December 2015. A total of 230 patients (mean age 76.9±9.9years; CHA2DS2-VASc 4.3±1.7; HAS-BLED 1.7±0.9) were included. Rates of stroke, major bleeding and intracranial bleeding were 0.4, 1.9 and 0.5 events per 100 patient-years, respectively. In this cohort of AF patients anticoagulated with rivaroxaban, despite patients being older and having a high thromboembolic risk, rates of stroke, major bleeding and intracranial bleeding were low.

Clinical profile, management and outcomes in a cohort of elderly and highly comorbid patients with nonvalvular atrial fibrillation treated with rivaroxaban in routine practice.

To analyze clinical profile and management of patients with nonvalvular atrial fibrillation treated with rivaroxaban in clinical practice according to age and to ascertain rates of thromboembolic and bleeding events during rivaroxaban therapy. Retrospective study of nonvalvular atrial fibrillation patients that started rivaroxaban therapy between May 2013 and February 2017 in the cardiology department of two hospitals from Huesca, Spain. A total of 137 patients (mean age 78.2±8.9years; CHA2DS2-VASc 3.5±1.3; HAS-BLED 1.6±0.7) were included. Comorbidity was common. After a mean duration of treatment of 30.5±17.2months, no strokes were reported. Rates of transient ischemic attack, major bleeding and intracranial bleeding were low. In this cohort of elderly and highly comorbid patients treated with rivaroxaban, rates of thromboembolic and bleeding events were low.

Real-Life Management of Venous Thromboembolism With Rivaroxaban: Results From EXperience VTE, an Italian Epidemiological Survey.

Two large randomized controlled trials examined the efficacy and safety of rivaroxaban for the treatment of venous thromboembolism (VTE). The aim of this epidemiological study was to analyze a cohort of Italian patients affected by VTE who were treated with rivaroxaban in clinical practice. The data were collected by physicians using an online electronic questionnaire. The study was performed during a 6-month period from January to June 2014. We analyzed the clinical characteristics, risk factors for VTE, comorbidities, diagnostic techniques, and treatments in the whole population and in the subgroups with deep vein thrombosis (DVT) only, pulmonary embolism (PE) only, and DVT+PE. Overall, 75.9% of patients were affected by DVT; 20% of patients had DVT and PE; and 4.8% of patients had only PE. Approximately 90% of patients were symptomatic upon diagnosis, and 46.3% of patients required hospitalization. More than half of the patients switched to rivaroxaban after receiving another anticoagulant therapy. The main reasons for changing treatment included difficulties in managing vitamin K antagonists, patient choice, and prothrombin time-international normalized ratio (PT-INR) instability. The switch to rivaroxaban occurred after a mean of 1.8 PT-INR measurements. Clinical characteristic were overall similar to those of patients enrolled in prior clinical trials evaluating the safety and efficacy of rivaroxaban.

Overall Effectiveness of Rivaroxaban in Patients with Pulmonary Embolism

PurposeDue to limited evidence on the impact of rivaroxaban in clinical practice, we compared the effectiveness of rivaroxaban versus standard of care (SOC) among patients in the Veterans Health Administration. MethodsAdult patients with continuous enrollment in a health plan with medical and pharmacy benefits for ≥12 months before and ≥3 months after an inpatient diagnosis of pulmonary embolism (PE) between October 1, 2011, and June 30, 2015, and a prescription claim for an anticoagulant during the index hospitalization, were included. SOC drugs were low-molecular-weight heparin, unfractionated heparin, and warfarin. Propensity score matching was used in comparing PE-related outcomes (recurrent venous thromboembolism, major bleeding, and death), hospital-acquired complications (HACs), health care resource utilization, and costs among patients receiving SOC versus rivaroxaban. We defined net clinical benefit as 1 minus the combined rate of PE-related outcomes and HACs. FindingsAmong 6746 patients with PE, 208 received rivaroxaban, 4641 received SOC and 1897 received other anticoagulants. Most (95%) were male; 22% were black. After 1:3 propensity score matching, there were 203 rivaroxaban and 609 SOC patients. During the 90-day follow-up, rivaroxaban users had similar rates of PE-related outcomes, but fewer had experienced at least 1 HAC (10.3% vs 15.9%; P = 0.0506), resulting in better net clinical benefit (82.8% vs 71.1%; P = 0.001). Rivaroxaban users had fewer outpatient visits per patient (17.0 vs 19.9; P = 0.0005), a similar rehospitalization rate (0.2 vs 0.3; P = 0.084), lesser inpatient costs (US $3501 vs $6189; P < 0.0001), lesser inpatient costs and lesser total costs ($10,545 vs $14,192; P = 0.0002). When the sample was limited to patients with low-risk PE, we found similar patterns. ImplicationsPatients with PE prescribed rivaroxaban had similar PE-related outcomes, but fewer HACs and lesser total costs, than did patients on SOC.

Pharmacoeconomic study on rivaroxaban vs conventional venous thromboembolism prophylaxis following elective total hip or knee replacement surgery in Serbia: Single centre study

Introduction: Venous thromboembolism (VTE) is often clinically unobservable, showing the first symptoms only after the patient has been discharged from the hospital, owing to which symptoms may not be recognized in time and serious complications may arise after hip or knee replacement surgery. The outcome for a patient who has had a symptomatic episode of VTE may be bad due to a risk of recurrent VTE and the development of postthrombotic syndrome. The annual incidence of VTE is around 80-180 cases in 100.000, based on population studies. Worldwide, orthopaedists and anaesthesiologists mostly refer to ACCP guidelines from America, or guidance from NICE and Scottish Medicines Consortium in Europe. All the guidelines include rivaroxaban as a therapy of choice for the prevention of VTE following elective arthroplasty as the therapy with rivaroxaban has shown both effectiveness and cost-savings. Many countries have included rivaroxaban as a medicine of first choice in the therapy for the above described indication. Aim: The objective of this analysis is to demonstrate cost-effectiveness of the new therapy with rivaroxaban versus conventional in VTE prophylaxis for patients undergoing elective hip or knee replacement surgery. Methodology: This paper is a part of the academic IV phase pharmacoecconomic study using extrapolation datas (RECORD 1, RECORD 2, RECORD 3) done in Serbia as single center expirience of Institute for Orthopaedic Surgery 'Banjica', in 2015. Information on drug prices, basic pharmacological characteristics, and on services of health institutions, are taken from the List of Drugs and Pricelist of the Republic Health Insurance Fund, as well as the Thromboembolism Prophylaxis Guide of the Institute 'Banjica'. The Incremental cost-effectiveness ratio (ICER) and Cost-utility analysis (CUA) have also been used in relation to the Quality-adjusted life-year (QALY). Furthermore, in the calculation the proposed price of a defined daily dose (DDD) of rivaroxaban was 3.36 EUR. Results: Total savings obtained annually through the application of rivaroxaban instead of usual prophylaxis (6,900 surgeries) could lead to cost savings of EUR 511,248.35 with the ICER value shows that therapy with rivaroxaban is dominant. Conclusions: The introduction of rivaroxaban in the therapy will enable patients to receive more conformable oral therapy with the same amount of health insurance resources spent, while on the other hand significant savings will be obtained owing to a decrease in the number of inpatient days in hospitals, as well as owing to the fact that regular control examinations of INR and number of blood platelets will not be necessary, which otherwise may amount to EUR 511,248.35annually for the said indication. The authors suggest support for the IV phase of the investigator initiated academic clinical trials with the intention of gaining security and personal experiences of doctors who use rivaroxaban in clinical practice.

Safety of Non-Vitamin K Antagonist Oral Anticoagulants in Clinical Practice: Focus on Rivaroxaban in Stroke Prevention in Patients With Atrial Fibrillation.

Despite direct oral anticoagulants (DOACs) have overcome the most relevant limitations of vitamin K antagonists, many patients with atrial fibrillation are not receiving the appropriate anticoagulant therapy. In addition, when patients are anticoagulated with DOACs, some of them are not taking the dose recommended in the summary of product characteristics. This may be related, at least in part, to the concern about the applicability of findings from randomized clinical trials to real-life patients. In this context, performing studies in daily clinical practice to assess the efficacy and safety of DOACs in real-world setting is mandatory. The aim of this review is to update the current evidence regarding safety of rivaroxaban in clinical practice. The Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) showed that rivaroxaban was at least as effective as warfarin for preventing stroke or systemic embolism, with similar rates of major bleeding but with lesser risk of intracranial and fatal bleedings. Data from noninterventional studies and registries have confirmed the good results of ROCKET-AF. Even more, rates of bleeding may be inferior in real-life patients, since they have a lower risk profile than those included in ROCKET-AF.

Rivaroxaban at Non-Valvular Atrial Fibrillation: a Prospective Study and Clinical Practice

The article presents an analytical review of the results of post-registration clinical studies on the efficacy and safety of rivaroxaban in nonvalvular atrial fibrillation (AF) to prevent stroke and other systemic thromboembolic complications. The main purpose of the first large prospective international observational study of rivaroxaban for stroke prevention in patients with non-valvular AF patients XANTUS was the analysis of efficacy and safety of rivaroxaban in clinical practice. Results of one year of observation of 6784 patients confirmed that rivaroxaban is effective and safe in real unselected population of patients with non-valvular AF and various stroke risk. The first Russian multicenter observational study Neuro-Xar dedicated to secondary prevention of stroke and systemic embolism, demonstrated the efficacy and safety of rivaroxaban in routine clinical practice. Lower risk of fatal intracranial and gastrointestinal bleeding was found in retrospective post-marketing studies, of rivaroxaban in the US, such as the PMSS and REVISIT-US. Rivaroxaban therapy was associated with reduced risk of the combined endpoint (ischemic stroke and intracranial hemorrhage).

Appropriateness of Dabigatran and Rivaroxaban Prescribing for Hospital Inpatients.

Recent approval of the new oral anticoagulants dabigatran and rivaroxaban has led to rapid changes in anticoagulant prescribing practices. Postmarketing reports have highlighted safety concerns with these agents, and their use outside of evidence-based recommendations was noted at the authors' centre. To determine the incidence of and risk factors associated with inappropriate prescribing of dabigatran and rivaroxaban. This retrospective cohort study investigated randomly selected dabigatran or rivaroxaban prescriptions for patients admitted to a tertiary teaching hospital between January 2010 and December 2012. Appropriateness of prescribing was determined from the documented indication, drug dosage, patient's renal function, and presence of drug interactions, if applicable. Among a total of 321 medication orders reviewed, the incidence of inappropriate use was 31.2% (34/109) for dabigatran and 26.9% (57/212) for rivaroxaban. Of the 97 reasons for inappropriate use that were identified, the most common were prescribing for an unapproved indication (49/97 [50.5%]), concomitant prescribing of another anticoagulant (22/97 [22.7%]), and high prescribed dose (9/97 [9.3%]). The prescribing service was found to be an independent risk factor for inappropriate prescribing (p = 0.041). Corrections were made to 23.1% (21/91) of the incorrect regimens before hospital discharge. In a sensitivity analysis using calculated ideal body weight to estimate renal function, the overall incidence of inappropriate prescribing increased to 31.5% (101/321). The proportion of patients with inappropriate prescribing of dabigatran or rivaroxaban in clinical practice was higher than expected. Educational interventions and pharmacy-led initiatives with a focus on appropriate indications, concomitant anticoagulant prescribing, and review of dosage regimens are recommended to improve patient safety.

Application of rivaroxaban in clinical practice: results of a prospective observational study XANTUS in patients with atrial fibrillation

In XANTUS study the safety and efficacy of factor Xa inhibitor rivaroxaban were evaluated in routine clinical practice in patients with non-valvular atrial fibrillation. In consecutive patients who started treatment with rivaroxaban, all adverse events were recorded every 3 months for 1 year. Conclusions of major bleeding, symptomatic thromboembolic complications (stroke, systemic embolism, transient ischemic attack, and myocardial infarction) and death from all causes were centrally adjudicated. In total 6784 patients were treated with rivaroxaban at 311 centers in Europe, Israel, and Canada, on average, 329 days. The mean CHADS2 and CHA2DS2-VASc scores were 2.0 and 3.4, respectively. Treatmentemergent major bleeding occurred in 128 patients (2.1 events per 100 patient-years), 118 (1.9 events per 100 patient-years) died, and 43 (0.7 events per 100 patient-years) suffered a stroke. XANTUS is the first international, prospective, observational study to describe the use of rivaroxaban in a broad non-valvular atrial fibrillation patient population. Rates of stroke and major bleeding were low in patients receiving rivaroxaban in routine clinical practice.

Rivaroxaban-Mediated Vascular Relaxation As a Potential Cause of Headaches and Dizziness

The availability of the direct Xa inhibitors apixaban, edoxaban and rivaroxaban in clinical practice is leading a paradigm shift in anticoagulation for the management of venous thromboembolism (VTE) and stroke prophylaxis in the context of non-valvular atrial fibrillation (AF). A common side effect experienced by patients receiving rivaroxaban in clinical trials was dizziness and headache, with a reported incidence of between 1 in 10 and 1 in 100 patients. Clinical experience has seen patients reporting rivaroxaban associated headaches and dizziness, leading to discontinuation of therapy. Given that widespread use of these agents is likely to be within an older adult population, it is important to understand the mechanism behind clinical observations which may then allow us to determine why some patients are affected more than others. We hypothesise that rivaroxaban directly causes vascular arteriodilation, resulting in headaches and dizziness requiring discontinuation of treatment.To test this hypothesis the effects of rivaroxaban on phenylephrine pre-contracted rat aortic rings was investigated. Thoracic aorta from male Sprague-Dawley rats (180-220g) were dissected and cut into rings of 2-3mm prior to being mounted under a preload tension of 1.5g in Krebs filled organ baths. Isometric tension of the rings was measured with isometric transducers (Danish Myo Technology, Aarhus, Denmark) digitised using a Power lab system. Following a phenylephrine dose-response curve the aortic rings were pre-contracted with 1 µM phenylephrine before measuring the relaxant effect of rivaroxaban (0.001-0.3 µM) or a similar volume of the vehicle dimethyl sulfoxide (DMSO). Statistical analysis was carried out using two-way ANOVA with Bonferroni's correction, where p<0.05 was considered significant.Exposure of aortic rings to both rivaroxaban and the vehicle DMSO caused relaxation. However, the relaxation observed with rivaroxaban was significantly greater than that observed with the vehicle (Fig 1).Our preliminary data suggests that rivaroxaban may have a direct arteriodilatory effect. This arteriodilatory effect of rivaroxaban may provide a possible explanation for dizziness and headaches experienced by some rivaroxaban treated patients. Further work is required to determine the underlying mechanism of rivaroxaban-mediated vaso-relaxant effect as well as determining if the other Xa inhibitors apixaban and edoxaban also share this physiological effect, and if so, to what extent. [Display omitted] DisclosuresPatel:Bayer plc: Research Funding. Arya:Bayer plc: Research Funding.

Abstract 11913: Early Nonadherence With Dabigatran and Rivaroxaban in Patients With Atrial Fibrillation

Background: Dabigatran and rivaroxaban are novel oral anticoagulants (NOACs) approved recently for stroke prevention in atrial fibrillation (AF). Although NOACs are more convenient than warfarin, their lack of monitoring, and for dabigatran, dosing frequency may predispose patients to nonadherence. Limited information is available on the adherence rates and related clinical outcomes for dabigatran and rivaroxaban in clinical practice. Methods: We conducted a population-based cohort study using administrative data of patients aged 65 years and over with AF, linking hospital discharge abstract and prescription claims databases in Ontario, Canada from April 2012 to March 2014. Nonadherence was measured as proportion of patients discontinuing dabigatran or rivaroxaban, defined as a gap in dabigatran or rivaroxaban prescription for ≥14 days within the first 6 months of therapy, and time to discontinuation. A multivariate Cox proportional hazards model was used to examine the association between drug discontinuation at any time, and the composite outcome of hospitalization for stroke, or death. Results: The cohort consisted of 15,857 dabigatran users and 10,119 rivaroxaban users, with women comprising 52% of each medication group. Mean age was 80.7±6.7 years for dabigatran, and 77.0±7.1 years for rivaroxaban patients. At 6-months, 36.5% of patients discontinued dabigatran (110mg: 37.4%; 150mg: 34.1%), while 32.1% of patients discontinued rivaroxaban. Median time to discontinuation was 240 days (IQR: 78-523) for dabigatran and 140 days (IQR: 52-283) for rivaroxaban. Risk of the composite outcome (stroke or death) was significantly higher for those who discontinued dabigatran [HR 1.78 (95% CI 1.62-1.95);p&lt;0.0001] or discontinued rivaroxaban [HR 3.07 (95% CI 2.54-3.72);p&lt;0.0001] compared with those who did not discontinue the medication. Conclusions: Within 6 months of initiation, discontinuation rates are high in clinical practice, with 1 in 4 patients discontinuing dabigatran, and 1 in 3 patients discontinuing rivaroxaban. There is an association between nonadherence with either dabigatran or rivaroxaban and significantly worse clinical outcomes following medication discontinuation.

Rivaroxaban as an oral anticoagulant for stroke prevention in atrial fibrillation.

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the developed world and is associated with a fivefold increase in the risk of stroke, accounting for up to 15% of strokes in the general population. The European Society of Cardiology now recommends direct oral anticoagulants, such as rivaroxaban, apixaban, and dabigatran, in preference to vitamin K antagonist therapy for the prevention of stroke in patients with A F. This review focuses on the direct Factor Xa inhibitor rivaroxaban, summarizing the properties that make rivaroxaban appropriate for anticoagulant therapy in this indication (including its predictable pharmacokinetic and pharmacodynamic profile and once-daily dosing regimen) and describing data from the Phase III ROCKET AF trial, which showed once-daily rivaroxaban to be noninferior to warfarin for the prevention of stroke in patients with nonvalvular AF. In this trial, similar rates of major and nonmajor clinically relevant bleeding were observed; however, when compared with warfarin, rivaroxaban was associated with clinically significant reductions in intracranial and fatal bleeding. On the basis of these results, rivaroxaban was approved in both the United States and the European Union for the prevention of stroke and systemic embolism in patients with nonvalvular AF. Subanalyses of ROCKET AF data showed rivaroxaban to have consistent efficacy and safety across a wide range of patients, and studies to confirm these results in real-world settings are underway. This review also describes practical considerations for treatment with rivaroxaban in clinical practice (including dose reductions in specific high-risk patients, eg, those with renal impairment), recommendations for the transition from vitamin K antagonists to rivaroxaban, the management of bleeding events, and the measurement of rivaroxaban exposure.

Rivaroxaban in Clinical Practice for Atrial Fibrillation With Special Reference to Prothrombin Time

Prothrombin time (PT) distribution in Japanese nonvalvular atrial fibrillation (NVAF) patients under rivaroxaban therapy remains to be clarified. Between May 2012 and July 2013, 115 NVAF patients received rivaroxaban (PT was measured in 94; reagent: recombiplastin). In these patients, (1) PT values were distributed widely from patient to patient and from peak to trough, (2) the time-dependence was obscure with sampling at any time in the outpatient clinic, and (3) the incidence of adverse events was too low for analyzing the relation with PT. We report the distribution of PT for Japanese NVAF patients under rivaroxaban therapy in real-world clinical practice.