Study design of GENERAL (general practitioners and embolism prevention in NVAF patients treated with rivaroxaban: Real‐life evidence): A multicenter prospective cohort study in primary care physicians to investigate the effectiveness and safety of rivaroxaban in Japanese patients with NVAF

Abstract

BackgroundRivaroxaban, a direct oral anticoagulant (DOAC), has become available for stroke prevention in patients with non-valular atrial fibrillation (NVAF). However, little is known about its effectiveness and safety when prescribed by general practitioners in real-life settings.MethodsGENERAL is a multicenter, prospective, non-interventional observational study of patients receiving rivaroxaban for NVAF in daily clinical practice prescribed specifically by general practitioners. The target number of participating medical institutions is 500–700 clinics with fewer than 20 beds and the target number of participants is 5000. The baseline clinical data, including antidementia medication and frailty, and follow-up data including concomitant treatment and outcomes until September 2018 (maximum three years) will be collected. The primary efficacy endpoints will be stroke and/or systemic embolism and the secondary endpoints will be major bleeding meeting the ISTH guidelines, non-major and clinically relevant bleeding, onset of symptomatic stroke (ischemic/hemorrhagic), systemic embolism, deep vein thrombosis/pulmonary thromboembolism, myocardial infarction and/or cardiovascular death, and systemic embolism. Based on the provided information, the event assessment committee will investigate the endpoint-related events. The annual incidence and predictive factors for primary/secondary endpoint will be investigated based on underlying disease, age, renal function, and CHADS2, CHA2DS2-VASC, and HAS-BLED scores using Cox regression. We will also compare the incidence of the primary/secondary endpoint between the present study, EXPAND study, and FUSHIMI AF registry study.ResultsThe results of this study are currently under investigation.ConclusionThis study will provide important information regarding the effectiveness and safety of rivaroxaban treatment in Japanese patients with NVAF among general practitioners.

Observational study of frailty in older Japanese patients with non-valvular atrial fibrillation receiving anticoagulation therapy

“…Similarly, the size of our study populations and the observation period should be considered when interpreting the results. The original GENERAL study was a single-arm observational study, and the sample size was determined based on the results of the previous studies, including from that of the western countries 12 . However, the actual observed events in the GENERAL study were fewer than expected.…”

“…This study was conducted as part of the GENERAL study. The details of the GENERAL study have been reported elsewhere 12 , 13 . In brief, GENERAL was a multicenter prospective observational study involving patients prescribed rivaroxaban for NVAF in daily clinical practice, specifically by ambulatory primary care physicians in Japan (UMIN000019135, NCT02633982).…”

“…The analysis plan for this report was originally planned as part of subgroup analyses 12 . The number of enrolled patients in the original study was derived from the results of previous studies, and sample size calculation for this study was not performed, considering imputation for missing variables and PS matching.…”

Effectiveness and Safety of Rivaroxaban by General Practitioners ― A Multicenter, Prospective Study in Japanese Patients With Non-Valvular Atrial Fibrillation (GENERAL) ―

“…However, the actual outcomes of rivaroxaban use in general practice remain unclear as the previous observational studies of this drug in patients with NVAF were mainly conducted by cardiovascular specialists in university and hospital settings. 7-10 Accordingly, we conducted a multicentre, prospective cohort study: the GENeral practitioners and Embolism pRevention in NVAF patients treated with RivAroxaban: real-Life evidence (GENERAL) study (UMIN000019135, NCT02633982), 11 to investigate the effectiveness and safety of rivaroxaban in Japanese patients with NVAF as prescribed by general practitioners. We also investigated the clinical events that occurred in high-risk patients (i.e., those of extreme age or exhibiting cognitive disorder or frailty) in this study.…”

“…The study design has been described previously (Figure 1). 11 In brief, the baseline clinical data, including that regarding cognitive dysfunction and frailty, and the follow-up data including concomitant treatment, were collected until September 2018 (maximum of 3 years). CHADS2, CHA2DS2-VASc (ischemic stroke risk), and HAS-BLED (major bleeding) scores were calculated using the baseline clinical data.…”