Abstract 20558: Rivaroxaban Reduces Early Cardiac Remodeling in Mice After Left Anterior Descending Artery (LAD) Ligation
Introduction: Rivaroxaban is a direct inhibitor of Factor Xa. Inhibition of several Factor Xa downstream pathways, such as protease-activated receptors 1 and 2, has been shown to reduce cardiac remodeling in vivo. The TIMI-51 trial demonstrated reduced mortality in patients with acute coronary syndrome that were treated with rivaroxaban.
Hypothesis: We assessed the hypothesis that rivaroxaban reduces cardiac remodeling when given early after myocardial infarction.
Methods: Wild-type mice underwent LAD ligation or sham operation and were fed either placebo or rivaroxaban (0.4 mg/g chow) beginning immediately after surgery. A second set of mice underwent LAD ligation and was started on rivaroxaban 3 days later. Echocardiography was performed on day 3, 7, 14, and 28.
Results: The ejection fraction after LAD ligation was significantly decreased at all time points compared to sham operated mice but relatively preserved in rivaroxaban-treated mice compared to placebo-treated mice (day 28: rivaroxaban 40.9±3.1% (n=9), placebo 19.6±3.9% (n=9), p<0.0001) (Figure). This difference was visible as early as day 3 (Figure). Hearts of rivaroxaban-treated mice were less dilated and had a preserved posterior wall compared to placebo treated mice on day 28 (rivaroxaban 0.83±0.11mm (n=9), placebo 0.50±0.10mm (n=9), p<0.05). Less fibrosis was observed in rivaroxaban-treated mice on day 28. Infarct size did not differ between the treatment groups on day 1 by TTC stain. The ejection fraction of mice that were started on rivaroxaban on day 3 (n=8) did not differ significantly from placebo-treated mice on day 28.
Conclusions: Rivaroxaban administered immediately after LAD ligation reduces cardiac remodeling by improving ejection fraction and reducing left ventricular dilatation and cardiac fibrosis. Failure of rivaroxaban to improve ejection fraction when started on day 3 suggests that rivaroxaban primarily affects early cardiac remodeling.
Author Disclosures: M.F. Bode: None. W.D. Bode: None. R. Vora: None. B.C. Cooley: None. N. Mackman: Other Research Support; Modest; Research support by Janssen.
- © 2016 by American Heart Association, Inc.