Comparative clinical and laboratory efficacy of low-dose innovator and generic rivaroxaban in patients with stable coronary artery disease

Aim.  To compare the clinical and laboratory efficacy of adding the original (Xarelto, Bayer, Germany) and generic (Kruoksaban, Ozon Pharmaceuticals, Russia) rivaroxaban to the standard treatment regimen at a dose of 2,5 mg twice daily in patients with stable coronary artery disease (CAD) with a high risk of ischemic events and a low risk of bleeding. Material and methods.  This single-center, open-label, randomized study enrolled 50 patients with stable CAD (25 patients each in the Xarelto and Kruoksaban groups). Primary efficacy endpoints were: Incidence of serious cardiovascular events (acute myocardial infarction; unstable angina; ischemic stroke). No significant differences in the dynamics of ADP- and TRAP-induced platelet aggregation, plasminogen activator inhibitor-1 (PAI-1) antigen levels (baseline, 24, and 120 hours after drug administration), and concentrations of the innovator and generic drugs (24 and 120 hours after drug administration). Secondary efficacy endpoints were cardiovascular and all-cause mortality, readmission (any non-elective hospital stay of more than 24 hours due to cardiac pathology worsening), coronary intervention within 30 days of treatment initiation. Safety endpoint was the incidence of bleeding events during 30 days of follow-up. Results.  Xarelto and Kruoksaban treatment significantly reduced ADP- and TRAP-induced platelet aggregation at 24 and 120 hours. The degree of aggregation suppression did not differ between the Xarelto and Kruoksaban groups. The changes of ADP-induced aggregation after 24 and 120 h were 7,16 (95% confidence interval (CI) 2,02-12,31) and 9,58 (95% CI 5,24-13,93) for Xarelto; 11,34 (95% CI 4,24-18,44) and 15,77 (95% CI 9,66-21,88) for Kruoksaban (p=0,326 for 24 h, p=0,094 for 120 h). The changes of TRAP-induced aggregation after 24 and 120 h were 4,72 [-0,13; 12,32] and 13,32 [4,90; 15,87] for Xarelto; 3,45 [1,73; 7,83] and 6,55 [0,51; 13,67] for Kruoksaban (p=0,749 for 24 h, p=0,258 for 120 h). No significant effect on plasma PAR-1 antigen levels was observed in either comparison group. Plasma rivaroxaban concentrations after 24 h were 30,82 (95% CI 23,87-37,76) for Xarelto and 27,41 (95% CI 20,48-34,32) for Kruoksaban (p=0,47). After 120 h, it was 24,71 [16,61; 40,65] and 20,07 [11,75; 31,76], respectively (p=0,08). During the 30-day follow-up period, no thrombotic or bleeding events were detected in the comparison groups. Conclusion.  The generic rivaroxaban (Kruoksaban, Ozon Pharmaceuticals, Russia) does not differ from the original one in platelet aggregation suppression and plasma rivaroxaban concentrations in patients with CAD.