P3592Safety analysis of rivaroxaban: a pooled analysis of the global XANTUS programme (real-world, prospective, observational studies for stroke prevention in patients with atrial fibrillation)

Abstract

Background: Combined anticoagulant/antiplatelet therapy in patients with atrial fibrillation (AF) undergoing coronary stenting (PCI) is associated with increased bleeding and cardiovascular events. An outcome relevant to patients is event-free days out of hospital. Purpose: To assess whether rivaroxaban (R) treatment strategies improve out-ofhospital adverse event-free duration compared with a standard warfarin regimen in patients with AF who undergo PCI. Methods: In the PIONEER AF-PCI trial, patients with AF undergoing PCI were randomized 1:1:1 to (1) 15 mg/d R + P2Y12 inhibitor (15 mg R n=669), (2) 2.5 mg bid R + dual-antiplatelet therapy (DAPT) (2.5 mg R n=668); or (3) vitamin K antagonist warfarin (VKA) + DAPT (n=654), and followed for 1 year. We collected the days out of the hospital free of any adverse event that was severe enough to prompt hospitalization. The adverse event that prompted a hospitalization had to have resolved even though the patient was out of the hospital to be counted as an event-free day. The figure compares the cumulative distribution of eventfree days and median number of event-free days (non-parametric Kruskal-Wallis † test). The proportion of subjects exceeding a given duration of adverse event free days (AEFD) was compared using the Wilcoxon test. Results: The 2.5 mg R + DAPT strategy was associated with greater median outof-hospital event-free days compared to VKA (p<0.0001). For any AEFD on the X axis, the proportion of subjects exceeding that time was significantly different across strata overall (p<0.0001; Figure). The proportion of subjects in the 2.5mg R + DAPT arm was significantly higher than the proportion in the VKA + DAPT group (p<0.0001). 89% of subjects in the 2.5 mg R + DAPT arm experienced >100 days of AEFD vs only 81% in the VKA + DAPT arm. Likewise, 81% of subjects in the 2.5 mg R + DAPT arm exhibited >300 days of AEFD vs only 74% in the VKA + DAPT arm. There was no statistical difference comparing the 15 mg R + P2Y12 to the VKA + DAPT group (p=0.47). Cumulative distribution of AEFD by TrxConclusions: Among patients with AF undergoing PCI, a rivaroxaban-based strategy increased event-free days out of hospital compared with a VKA + DAPT strategy, a patient-centered outcome that should be considered in the assessment of net clinical benefit. Acknowledgement/Funding: This study was funded by the sponsors, Janssen Scientific Affairs, LLC and Bayer. (ESC 2016) guidelines on atrial fibrillation focused recommendations for oral anticoagulation (OAC) in patients with ≥2 non-gender CHA2DS2-VASc stroke risk factors (ie. CHA2DS2-VASc score ≥2 in males, ≥3 in females), in contrast to the 2012 guidelines (ESC 2012). The impact on stroke and/or death with the change in treatment thresholds consequent upon the change in guidelines requires evaluation. Methods: We assessed the rates of stroke and/or death, major bleeding and the net clinical benefit (NCB) in patients at low risk (CHA2DS2-VASc score 0 in males, 1 in females; no antithrombotic therapy recommended); intermediate ...

Understanding the Value of Real-World Evidence: Focus on Stroke Prevention in Atrial Fibrillation with Rivaroxaban

“…Treatment-emergent major outcomes were adjudicated by one Central Adjudication Committee to minimize reporting bias. 16 In total, 16,187 patients were screened between June 2012 and December 2014, of whom 11,121 patients were included in the analysis. Patients from 47 countries were grouped as follows: Western Europe/Canada/Israel (47.5%), Eastern Europe (23.2%), East Asia (20.1%), the Middle East/Africa (6.2%) and Latin America (3.0%).…”

“…Patients from 47 countries were grouped as follows: Western Europe/Canada/Israel (47.5%), Eastern Europe (23.2%), East Asia (20.1%), the Middle East/Africa (6.2%) and Latin America (3.0%). 16 In total, 8,540 (76.8%) patients received rivaroxaban and were followed up for at least the full 12-month study period; treatment was prematurely ended in 2,566 (23.1%) patients, of whom 724 (6.5%) discontinued rivaroxaban due to AEs. More than 96% of the pooled XANTUS population did not experience any treatment-emergent major bleeding, stroke/non-CNS SE or all-cause death.…”

“…Results were also consistent with those of the Phase III ROCKET AF study. 13,16 The Growing Use of Claims Databases to Inform Clinical Practice 19 and national healthcare databases, such as the Danish Nationwide Database. [20][21][22] Other claims data are drawn from multiple different payers and are assembled by specific health analytic companies, such as Truven Mar-ketScan 23 and Optum Insight.…”

Possibilities of Using Rivaroxaban in Elderly Patients with Atrial Fibrillation: Data from Randomized Studies and Real Clinical Practice

“…Высокая приверженность к терапии ривароксабаном может быть следствием благоприятного профиля эффективности и безопасности в реальной клинической практике, на что указывают результаты крупнейшей проспективной наблюдательной исследовательской программы XANTUS [24,25]. Программа XANTUS объединяет 3 исследования, выполненные в различных географических регионах с участием более 11000 больных ФП из 47 стран: XANTUS (Западная и Восточная Европа, Канада и Израиль), XANAP (Азиатско-Тихоокеанский регион) и XANTUS-EL (Восточная Европа, Ближний Восток, Африка и Латинская Америка).…”

Risk Controlling of Gastrointestinal Bleeding in Comorbid Patients with Cardiovascular Diseases

“…При этом в анализе субпопуляции исследования ARISTOTLE у пациентов с ХСН с сохранной систолической функцией выявлялась бóльшая частота ЖКК в группе апиксабана по сравнению с варфарином [31]. В тоже время наблюдательное проспективное исследование с ривароксабаном XANTUS pooled [32] включало пациентов со средним баллом по CHADS 2 равным 2,0, что очень близко к среднему CHADS 2 в исследовании ARISTOTLE. Частота ЖКК в XANTUS составила 0,6%, что соответствует частоте ЖКК в ARISTOTLE -0,8%.…”