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. 2022 Nov;36(6):2009-2015.
doi: 10.1111/jvim.16572. Epub 2022 Nov 18.

Anticoagulant effects of rivaroxaban, prednisone, alone and in combination, in healthy dogs

Paige M Hafner  1 , Andrew J Mackin  1 , Robert W Wills  2 , Marjory B Brooks  3 , John M Thomason  1
Affiliations

Anticoagulant effects of rivaroxaban, prednisone, alone and in combination, in healthy dogs

Paige M Hafner et al. J Vet Intern Med. 2022 Nov.

Abstract

Background: The potential effects of glucocorticoid administration on rivaroxaban's anticoagulant bioactivity in dogs, and an appropriate rivaroxaban dosage regimen for dogs receiving glucocorticoid therapy are unknown.

Hypothesis/objectives: The objective was to determine whether glucocorticoid administration influences the anticoagulant effects of rivaroxaban in healthy dogs. We hypothesized that administration of rivaroxaban and prednisone would reduce the anticoagulant intensity compared with rivaroxaban alone.

Animals: Nine healthy dogs.

Methods: Randomized, cross-over study. Dogs were administered prednisone (2 mg/kg, PO, q24h), rivaroxaban (1.5 mg/kg, PO, q24h), or prednisone and rivaroxaban, and the coagulation status was evaluated using prothrombin time (PT), and rivaroxaban-calibrated anti-Xa activity (RIVA, results were log10 transformed for analysis), before drug administration and on days 2, 4, and 8. Linear mixed models and correlation were used to evaluate associations in variables (P < .05 was considered significant).

Results: There were no differences in RIVA results for the rivaroxaban and prednisone/rivaroxaban groups on day 8 (P = .599, median 87 [range 45-156] to 167 [56-333], respectively, median difference 90 ng/mL [95% CI:87.3-161.8]) There was a strong correlation between RIVA and PT results when days 2, 4, and 8 were combined (r = .846, P < .001), and increased during drug administration, day 2 (r = .810, P < .001), day 4 (r = .863, P < .001), and day 8 (r = .885, P < .001).

Conclusions and clinical importance: Clotting times in the PT correlate with rivaroxaban levels and may prove useful for drug monitoring. Prednisone administration had no apparent influence on the anticoagulant effects of rivaroxaban in healthy dogs, suggesting that combined therapy will not require dosage adjustments.

Keywords: corticosteroid; glucocorticoid; immune-mediated hemolytic anemia; thromboprophylaxis.

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Conflict of interest statement

Marjory Brooks is the Director of the Comparative Coagulation Section of the Diagnostic Laboratory at the Cornell University College of Veterinary Medicine. No other authors have a conflict of interest.

Figures

FIGURE 1
FIGURE 1
PT values from 9 dogs treated with prednisone, rivaroxaban, and prednisone/rivaroxaban for 8 days. The box and whiskers plot demonstrate the median (line), interquartile range (box), and total range (whiskers). *Indicates a significant (P < .05) difference from before treatment (day 0) within a treatment group; #Indicates a significant (P < .05) difference from the prednisone group on the corresponding day
FIGURE 2
FIGURE 2
RIVA values from 9 dogs treated with prednisone, rivaroxaban, and prednisone/rivaroxaban for 8 days. The box and whiskers plot demonstrate the median (line), interquartile range (box), and total range (whiskers). *Indicates a significant (P < .05) difference from day 0 within a treatment group; #Indicates a significant (P < .05) difference from the prednisone group on the corresponding day
FIGURE 3
FIGURE 3
ACT values from 9 dogs treated with prednisone, rivaroxaban, and prednisone/rivaroxaban for 8 days. The box and whiskers plot demonstrate the median (line), interquartile range (box), and total range (whiskers). *Indicates a significant (P < .05) difference from day 0 within a treatment group; #Indicates a significant (P < .05) difference from the prednisone group on the corresponding day
FIGURE 4
FIGURE 4
CR values from 9 dogs treated with prednisone, rivaroxaban, and prednisone/rivaroxaban for 8 days. The box and whiskers plot demonstrate the median (line), interquartile range (box), and total range (whiskers). *Indicates a significant (P < .05) difference from day 0 within a treatment group; #Indicates a significant (P < .05) difference from the prednisone group on the corresponding day
FIGURE 5
FIGURE 5
Scatterplot showing the relationship between log10Riva (rivaroxaban‐specific anti‐Xa activity [RIVA]) and PT (seconds) for 9 dogs treated with prednisone, rivaroxaban, and prednisone/rivaroxaban for 8 days. The correlation (r) and the associated significance (P‐value) are displayed at the top of the graph
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