Thomas Evers

Real-world persistence and adherence to oral anticoagulation for stroke risk reduction in patients with atrial fibrillation

AIM To assess persistence and adherence to rivaroxaban, dabigatran, and vitamin K antagonist (VKA) treatment in primary care patients with non-valvular atrial fibrillation (AF) newly starting anticoagulant therapy. METHODS AND RESULTS Prescription data for oral anticoagulants were obtained from 7265 eligible patients from primary care practices across Germany. Persistence with and adherence to anticoagulation were assessed in anticoagulant-naïve patients with AF newly treated with dabigatran, rivaroxaban, or VKA during follow-up periods of at least 180 days, respectively 360 days after the prescription date. Persistence probabilities after 180 days were 66.0% for rivaroxaban, 60.3% for dabigatran, and 58.1% for VKA (P < 0.001 for rivaroxaban vs. VKA and P = 0.008 for rivaroxaban vs. dabigatran). After 360 days, persistence probabilities were 53.1, 47.3, and 25.5%, respectively (P < 0.001 for rivaroxaban and dabigatran vs. VKA). Considering the development over 360 days rivaroxaban demonstrated a better persistence compared with dabigatran (P = 0.026). Male gender and the presence of diabetes mellitus were associated with increased persistence, while renal impairment and antiplatelet drug use decreased persistence. High adherence (MPR ≥0.80) was observed in 61.4% of rivaroxaban users and in 49.5% of dabigatran users, with means of 0.76 [95% confidence interval (CI) 0.74-0.78] for rivaroxaban and 0.67 (95% CI 0.65-0.69) for dabigatran (P < 0.001). CONCLUSIONS Rivaroxaban and dabigatran demonstrated better persistence than VKA at Day 360. Furthermore, rivaroxaban was associated with better persistence and adherence than dabigatran. Further studies are needed to identify factors responsible for this difference and evaluate the impact on outcomes.

Real-world evidence of stroke prevention in patients with nonvalvular atrial fibrillation in the United States: the REVISIT-US study

Abstract Background: Little data exists regarding the effectiveness and safety of rivaroxaban or apixaban versus warfarin in nonvalvular atrial fibrillation (NVAF) patients treated outside of clinical trials. Methods: This was a retrospective study using MarketScan claims from January 2012 to October 2014. We included adults, newly initiated on rivaroxaban, apixaban or warfarin, with a baseline CHA2DS2-VASc score ≥2, ≥2 diagnosis codes for NVAF and ≥180 days of continuous medical and prescription benefits. Patients with a prior stroke, systemic embolism or intracranial hemorrhage (ICH) were excluded. Eligible rivaroxaban or apixaban users were 1:1 propensity-score matched individually to warfarin users. Cox regression was performed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for rivaroxaban and apixaban versus warfarin for the combined endpoint of ischemic stroke or ICH and each endpoint individually. Results: Upon matching 11,411 rivaroxaban to 11,411 warfarin users, rivaroxaban was associated with a significant reduction of the combined endpoint of ischemic stroke or ICH versus warfarin (HR = 0.61, 95% CI = 0.45–0.82). ICH was significantly (HR = 0.53, 95% CI = 0.35–0.79) and ischemic stroke nonsignificantly reduced (HR = 0.71, 95% CI = 0.47–1.07) by rivaroxaban versus warfarin. After matching 4083 apixaban and 4083 warfarin users, apixaban was found to nonsignificantly reduce the combined endpoint of ischemic stroke or ICH versus warfarin (HR = 0.63, 95% CI = 0.35–1.12) and to reduce ICH risk (HR = 0.38, 95% CI = 0.17–0.88). Ischemic stroke risk was nonsignificantly increased with apixaban (HR = 1.13, 95% CI = 0.49–2.63) versus warfarin. Limitations: Sample size and number of combined events observed were relatively small. Residual confounding could not be ruled out. Conclusions: Rivaroxaban and apixaban were associated with less ICH than warfarin and both are likely associated with reductions in the combined endpoint. Further investigation to validate the numerically higher rate of ischemic stroke with apixaban versus warfarin is required.

REal-LIfe Evidence of stroke prevention in patients with atrial Fibrillation — The RELIEF study

Introduction: Limited data is available on real-world outcomes in rivaroxaban compared to vitamin K antagonist (VKA) users with non-valvular atrial fibrillation (NVAF). Hypothesis: To assess the ef...

Treatment Persistence and Discontinuation with Rivaroxaban, Dabigatran, and Warfarin for Stroke Prevention in Patients with Non-Valvular Atrial Fibrillation in the United States.

A retrospective cohort analysis of the US MarketScan claims databases was performed to compare persistence and discontinuation rates between the vitamin K antagonist warfarin and the non-vitamin K antagonist oral anticoagulants rivaroxaban and dabigatran in patients with non-valvular atrial fibrillation. The analysis included adult patients with non-valvular atrial fibrillation newly initiated on rivaroxaban, dabigatran, or warfarin between November 1, 2011 and December 31, 2013, with a baseline CHA2DS2-VASc score ≥2, two or more non-valvular atrial fibrillation diagnosis codes (427.31), and ≥6 months’ continuous medical and pharmacy benefit enrollment before oral anticoagulant initiation. Propensity score matching was performed to match patients receiving rivaroxaban with those receiving dabigatran (1:1) and warfarin (1:1). Patients were followed until the first event of inpatient death, end of continuous enrollment, or end of study period. Medication persistence was defined as absence of a refill gap of >60 days. Discontinuation was defined as no additional refill for >90 days and through to end of follow-up. Hazard ratios (HRs) of oral anticoagulant persistence and discontinuation were estimated using Cox proportional hazard models. In total, 3,2634 patients were included (n = 10878/oral anticoagulant group). Rivaroxaban was associated with better persistence than both dabigatran (HR 0.64, 95% confidence interval [CI] 0.62–0.67) and warfarin (HR 0.62, 95% CI 0.59–0.64) and lower discontinuation than dabigatran (HR 0.61, 95% CI 0.58–0.64) and warfarin (HR 0.65, 95% CI 0.62–0.68). Real-world analysis of oral anticoagulant use may reveal whether the relatively high persistence/low discontinuation demonstrated for rivaroxaban translates into lower rates of stroke.

Patient-reported treatment satisfaction and budget impact with rivaroxaban vs. standard therapy in elective cardioversion of atrial fibrillation: a post hoc analysis of the X-VeRT trial

Abstract Aims We compared patient-reported treatment satisfaction and the economic impact of anticoagulation therapy with rivaroxaban vs. vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation undergoing elective cardioversion procedures. Methods and results The current study is a post hoc analysis of the prospective, multicentre X-VeRT (EXplore the efficacy and safety of once-daily oral riVaroxaban for the prevention of caRdiovascular events in subjects with non-valvular aTrial fibrillation scheduled for cardioversion) trial. Patient-reported treatment satisfaction with anticoagulation therapy was assessed using the Treatment Satisfaction Questionnaire for Medication version II in seven countries (US, UK, Canada, Germany, France, Italy, and the Netherlands). An economic model was also developed to estimate the impact of postponed cardioversions for two countries (UK and Italy). This model estimated the total costs of cardioversion, taking into consideration the costs for drug therapy (including extended treatment duration due to cardioversion postponement), international normalized ratio monitoring of VKAs, the cardioversion procedure, and rescheduling the procedure. These costs were linked to the respective X-VeRT study data to estimate the total costs. Patients receiving rivaroxaban in the delayed cardioversion group had significantly higher scores for Convenience, Effectiveness, and Global satisfaction (81.74 vs. 65.78; 39.41 vs. 32.95; and 82.07 vs. 66.74, respectively; P < 0.0001). Based on the total patient population included in the treatment satisfaction substudy (n = 632) in the delayed cardioversion group in X-VeRT, the use of rivaroxaban was estimated to result in a saving of £421 and €360 per patient in UK and Italian settings, respectively. Conclusion The use of rivaroxaban in the setting of cardioversion resulted in greater patient satisfaction and cost savings, compared with that of VKA.

Impact of Switching From a Vitamin K Antagonist to Rivaroxaban on Satisfaction With Anticoagulation Therapy: The XANTUS‐ACTS Substudy

The efficacy, safety, and ease of use of rivaroxaban may reduce anticoagulation‐treatment burden and improve nonvalvular atrial fibrillation (NVAF) patient satisfaction compared with vitamin K antagonists (VKAs).

Clinical and economic impact of rivaroxaban on the burden of atrial fibrillation: The case study of Japan

Abstract Objectives: Atrial fibrillation (AF) affects an estimated 1.5 million individuals in Japan, increasing their stroke risk and imposing considerable costs on the Japanese healthcare system. To reduce stroke incidence, guidelines recommend using anticoagulants in moderate-to-high risk non-valvular AF (NVAF) patients; however, many patients receive no treatment, aspirin only, or remain poorly-controlled on vitamin K antagonists (VKAs) due to high VKA discontinuation rates and non-adherence to guidelines. A prevalence-based Markov model was developed to estimate the clinical and budgetary impact of treating these patients with XareltoTM (rivaroxaban, Bayer AG) in Japan. Methods: Population, baseline risk of events, and associated management costs were estimated using data from Japanese publications where available. Treatment efficacy and safety were derived from published data and the J-ROCKET AF trial. Drug and physician visit costs were based on data from the Ministry of Health, Labor, and Welfare, the J-ROCKET AF trial, and Japanese clinical guidelines. Results: This model demonstrates that increased use of rivaroxaban in inadequately-managed NVAF patients could avoid 456 081 non-fatal ischemic strokes (IS) and 76 975 cardiovascular deaths over 10 years in Japan. This clinical benefit offsets the increased incidence of myocardial infarctions and anticoagulant-related bleeding. Decreased event costs could lead to a ¥188.4 billion decrease in net spending over the analysis time horizon. Conclusions: Introducing rivaroxaban may decrease the burden of NVAF in Japanese society. From a clinical perspective, the reduction in IS and embolic events outweighs the increased risk of anticoagulant-related bleeding; from an economic perspective, reduced event costs offset drug and physician visit costs, resulting in cost savings.