Abstract
BackgroundHeart failure (HF) is considered to be a prothrombotic condition and it has been suggested that coagulation factors contribute to maladaptive cardiac remodelling via activation of the protease-activated receptor 1 (PAR1). We tested the hypothesis that anticoagulation with the factor Xa (FXa) inhibitor apixaban would ameliorate cardiac remodelling in rats with HF after myocardial infarction (MI).Methods and ResultsMale Sprague-Dawley rats were either subjected to permanent ligation of the left ascending coronary artery (MI) or sham surgery. The MI and sham animals were randomly allocated to treatment with placebo or apixaban in the chow (150 mg/kg/day), starting 2 weeks after surgery. Cardiac function was assessed using echocardiography and histological and molecular markers of cardiac hypertrophy were assessed in the left ventricle (LV). Apixaban resulted in a fivefold increase in anti-FXa activity compared with vehicle, but no overt bleeding was observed and haematocrit levels remained similar in apixaban- and vehicle-treated groups. After 10 weeks of treatment, LV ejection fraction was 42 ± 3% in the MI group treated with apixaban and 37 ± 2 in the vehicle-treated MI group (p > 0.05). Both vehicle- and apixaban-treated MI groups also displayed similar degrees of LV dilatation, LV hypertrophy and interstitial fibrosis. Histological and molecular markers for pathological remodelling were also comparable between groups, as was the activity of signalling pathways downstream of the PAR1 receptor.ConclusionFXa inhibition with apixaban does not influence pathological cardiac remodelling after MI. These data do not support the use of FXa inhibitor in HF patients with the aim to amend the severity of HF.Graphical
Highlights
Heart failure is a major global health problem that is reaching epidemic proportions in the near future [1, 2]
Our findings are in line with the results from the COMMANDER heart failure (HF) trial and do not support the use of factor Xa (FXa) inhibitor in HF patients with the aim to amend the severity of HF
FXa inhibition with apixaban does not influence pathological cardiac remodelling after a myocardial infarction (MI). These data do not support the use of FXa inhibitor in HF patients with the aim to amend the severity of HF
Summary
Heart failure is a major global health problem that is reaching epidemic proportions in the near future [1, 2]. Heart failure (HF) is considered to be a prothrombotic condition and it has been suggested that coagulation factors contribute to maladaptive cardiac remodelling via activation of the protease-activated receptor 1 (PAR1). Apixaban resulted in a fivefold increase in anti-FXa activity compared with vehicle, but no overt bleeding was observed and haematocrit levels remained similar in apixaban- and vehicle-treated groups. Histological and molecular markers for pathological remodelling were comparable between groups, as was the activity of signalling pathways downstream of the PAR1 receptor. Conclusion FXa inhibition with apixaban does not influence pathological cardiac remodelling after MI.
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