Key result
Rivaroxaban significantly reduced atrial fibrillation inducibility to 33% compared with 93% for vehicle and 80% for warfarin in spontaneously hypertensive rats.
Why the study?
Activated factor X contributes to chronic inflammation via PAR2 and might play a role in AF arrhythmogenesis, but whether PAR2 signaling contributes to AF arrhythmogenesis and whether rivaroxaban prevents AF were unknown.
Does rivaroxaban or PAR2 deficiency reduce AF inducibility and atrial remodeling in animal models?
Does rivaroxaban or PAR2 deficiency reduce AF inducibility and atrial remodeling in animal models?
Absolute Event Rate: 33% vs 93%
p-value: p=<0.01
Rivaroxaban reduces AF inducibility and atrial inflammation in animal models, suggesting the FXa-PAR2 signaling pathway is a potential therapeutic target for preventing AF.
PAR2 signaling may promote AF in Ang II mouse models; leaves open whether rivaroxaban prevents human AF.
BACKGROUND: Activated factor X (FXa), which contributes to chronic inflammation via protease-activated receptor 2 (PAR2), might play an important role in atrial fibrillation (AF) arrhythmogenesis. This study aimed to assess whether PAR2 signaling contributes to AF arrhythmogenesis and whether rivaroxaban ameliorates atrial inflammation and prevents AF. METHODS AND RESULTS: In Study 1, PAR2 deficient (PAR2-/-) and wild-type mice were infused with angiotensin II (Ang II) or a vehicle via an osmotic minipump for 2 weeks. In Study 2, spontaneously hypertensive rats (SHRs) were treated with rivaroxaban, warfarin, or vehicle for 2 weeks after 8 h of right atrial rapid pacing. The AF inducibility and atrial remodeling in both studies were examined. Ang II-treated PAR2-/- mice had a lower incidence of AF and less mRNA expression of collagen1 and collagen3 in the atrium compared to wild-type mice treated with Ang II. Rivaroxaban significantly reduced AF inducibility compared with warfarin or vehicle. In SHRs treated with a vehicle, rapid atrial pacing promoted gene expression of inflammatory and fibrosis-related biomarkers in the atrium. Rivaroxaban, but not warfarin, significantly reduced expression levels of these genes. CONCLUSIONS: The FXa-PAR2 signaling pathway might contribute to AF arrhythmogenesis associated with atrial inflammation. A direct FXa inhibitor, rivaroxaban, could prevent atrial inflammation and reduce AF inducibility, probably by inhibiting the pro-inflammatory activation.
No takes yet. Share an insight, caveat, or question.
Matsuura et al. (2021) studied Atrial Fibrillation (n=71). Rivaroxaban vs. Vehicle or Warfarin (0.2 mg/kg/day) was evaluated on Atrial fibrillation inducibility with right atrial burst pacing (p=<0.01). Rivaroxaban significantly reduced atrial fibrillation inducibility to 33% compared with 93% for vehicle and 80% for warfarin in spontaneously hypertensive rats.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: