Comparisons of Rivaroxaban Following Different Dosage Criteria (ROCKET AF or J-ROCKET AF Trials) in Asian Patients With Atrial Fibrillation

Yi-Hsin Chan, Hsin-Fu Lee, Chun-Li Wang, Shang-Hung Chang, Chih-Hsin Yeh, Tze-Fan Chao, Yung-Hsin Yeh, Shih-Ann Chen, Chi-Tai Kuo, Yi-Hsin Chan, Hsin-Fu Lee, Chun-Li Wang, Shang-Hung Chang, Chih-Hsin Yeh, Tze-Fan Chao, Yung-Hsin Yeh, Shih-Ann Chen, Chi-Tai Kuo

Abstract

Background The ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) evaluated rivaroxaban (20/15 mg/d) versus warfarin in patients with atrial fibrillation. A separate trial, J-ROCKET AF (Japanese ROCKET AF), compared rivaroxaban (15/10 mg/d) and warfarin in Japanese patients with atrial fibrillation. Data about rivaroxaban following J-ROCKET AF criteria compared with warfarin and ROCKET AF dosage were limited. Methods and Results This retrospective study used medical data from a multicenter healthcare provider in Taiwan that included 3162 patients taking rivaroxaban. Among 2320 patients with an estimated glomerular filtration rate (eGFR) ≥50 mL/min per 1.73 m2, 384 and 1936 patients followed the ROCKET AF (20 mg/d) and J-ROCKET AF (15 mg/d) recommendation, respectively. Among 842 patients with an eGFR <50 mL/min per 1.73 m2, 422 and 420 patients followed the ROCKET AF (15 mg/d) and J-ROCKET AF (10 mg/d) recommendation, respectively. A total of 2053 patients with atrial fibrillation receiving warfarin were identified. Rivaroxaban following either ROCKET AF or J-ROCKET AF dosage criteria was associated with a comparable risk of thromboembolism but a lower risk of bleeding than warfarin. For patients with an eGFR ≥50 mL/min per 1.73 m2, risks of clinical events did not differ significantly between the 2 dosage criteria of rivaroxaban. For patients with an eGFR <50 mL/min per 1.73 m2, the ROCKET AF dosage was associated with a higher risk of major bleeding compared with the J-ROCKET AF dosage (hazard ratio, 2.70; P=0.0445) without significant differences regarding the risk of ischemic events. Conclusions In Asian patients with atrial fibrillation, the J-ROCKET AF dosage was as effective as the ROCKET AF dosage irrespective of renal function. The risk of major bleeding was lower with the J-ROCKET AF dosage in patients with an eGFR <50 mL/min per 1.73 m2. Compared with warfarin, rivaroxaban following either dosage criteria was effective and even safer.

Keywords: J‐ROCKET AF; ROCKET AF; atrial fibrillation; factor Xa inhibitor; mortality; rivaroxaban; warfarin.

Figures

Figure 1
Figure 1
Enrollment of patients with nonvalvular atrial fibrillation (NVAF). There were 2320 and 842 patients with NVAF with estimated glomerular filtration rate (eGFR) ≥50 mL/min per 1.73 m2 and eGFR <50 mL/min per 1.73 m2 taking rivaroxaban, respectively, enrolled in this study from June 1, 2012, to December 31, 2017. Among the 2320 patients with eGFR ≥50 mL/min per 1.73 m2, there were 384 and 1936 patients following the ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) (20 mg/d) and J‐ROCKET AF (Japanese ROCKET AF) (15 mg/d) dosage criteria, respectively. Among the 842 patients with eGFR <50 mL/min per 1.73 m2, there were 422 and 420 patients following the ROCKET AF (15 mg/d) and J‐ROCKET AF (10 mg/d) dosage criteria, respectively. AF indicates atrial fibrillation.
Figure 2
Figure 2
Forest plot of hazard ratio (HR) and 95% CI for patients with nonvalvular atrial fibrillation taking rivaroxaban following the ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) dosage criteria or J‐ROCKET AF (Japanese ROCKET AF) dosage criteria vs patients taking warfarin. Patients taking rivaroxaban following either the ROCKET AF (20/15 mg/d) or J‐ROCKET AF (15/10 mg/d) dosage criteria showed a comparable risk of ischemic stroke or systemic embolism (IS/SE) and a lower risk of acute myocardial infarction (AMI), mortality, intracranial hemorrhage (ICH), and all major bleeding than patients taking warfarin after baseline covariate adjustment. GIB indicates gastrointestinal bleeding.
Figure 3
Figure 3
Forest plot of hazard ratio (HR) and 95% CI for rivaroxaban following the ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) dosage criteria vs J‐ROCKET AF (Japanese ROCKET AF) dosage criteria in patients with nonvalvular atrial fibrillation with estimated glomerular filtration rate (eGFR) ≥50 mL/min per 1.73 m2 and eGFR <50 mL/min per 1.73 m2. For patients with eGFR >50 mL/min per 1.73 m2, following the ROCKET AF dosage criteria (20 mg/d) was associated with a comparable risk of ischemic stroke or systemic embolism (IS/SE) and major bleeding to following the J‐ROCKET AF dosage criteria (15 mg/d) after baseline covariate adjustment. For patients with eGFR <50 mL/min per 1.73 m2, following the ROCKET AF dosage criteria (15 mg/d) was associated with a higher risk of major bleeding than following the J‐ROCKET AF dosage criteria (10 mg/d) after baseline covariate adjustment. AMI indicates acute myocardial infarction; GIB, gastrointestinal bleeding; ICH, intracranial hemorrhage.

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