Background

Rivaroxaban is a direct inhibitor of activated Factor X (FXa), an anti-inflammatory protein exerting a protective effect on the cardiac valve and vascular endothelium. We compare the effect of Warfarin and Rivaroxaban on inflammation biomarkers and their contribution to heart valve calcification progression and renal preservation in a population of atrial fibrillation (AF) patients with chronic kidney disease (CKD) stage 3b – 4.

Methods

This was an observational, multicenter, prospective study enrolling 347 consecutive CKD stage 3b – 4 patients newly diagnosed with AF: 247 were treated with Rivaroxaban and 100 with Warfarin. Every 12 months, we measured creatinine levels and cardiac valve calcification via standard trans-thoracic echocardiogram, while plasma levels of inflammatory mediators were quantified by ELISA at baseline and after 24 months.

Results

Over a follow-up of 24 months, long-term treatment with Rivaroxaban was associated with a significative reduction of cytokines. Patients treated with Rivaroxaban experienced a more frequent stabilization/regression of valve calcifications comparing with patients treated with Warfarin. Rivaroxaban use was related with an improvement in kidney function in 87.4% of patients, while in those treated with Warfarin was reported a worsening of renal clearance in 98% of cases. Patients taking Rivaroxaban experienced lower adverse events (3.2% vs 49%, p-value <0.001).

Conclusions

Our findings suggest that Rivaroxaban compared to Warfarin is associated with lower levels of serum markers of inflammation. The inhibition of FXa may exert an anti-inflammatory effect contributing to reduce the risk of cardiac valve calcification progression and worsening of renal function.

中文翻译：

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直接口服抗凝治疗对心脏瓣膜钙化、肾脏保护和炎症调节的新证据

背景

利伐沙班是活化因子 X (FXa) 的直接抑制剂，FXa 是一种抗炎蛋白，对心脏瓣膜和血管内皮具有保护作用。我们比较了华法林和利伐沙班对炎症生物标志物的影响及其对心房颤动 (AF) 慢性肾脏病 (CKD) 3b-4 期患者的心脏瓣膜钙化进展和肾脏保护的贡献。

方法

这是一项观察性、多中心、前瞻性研究，连续招募了 347 名 CKD 3b 期 - 4 名新诊断为 AF 的患者：247 名接受利伐沙班治疗，100 名接受华法林治疗。每 12 个月，我们通过标准的经胸超声心动图测量肌酐水平和心脏瓣膜钙化，同时在基线和 24 个月后通过 ELISA 量化炎症介质的血浆水平。

结果

在 24 个月的随访中，利伐沙班的长期治疗与细胞因子的显着减少有关。与接受华法林治疗的患者相比，接受利伐沙班治疗的患者瓣膜钙化稳定/消退的频率更高。在 87.4% 的患者中，利伐沙班的使用与肾功能的改善有关，而在华法林治疗的患者中，98% 的患者肾清除率恶化。服用利伐沙班的患者不良事件较少（3.2% 对 49%，p值 <0.001）。

结论

我们的研究结果表明，与华法林相比，利伐沙班与较低水平的炎症血清标志物有关。FXa 的抑制可能发挥抗炎作用，有助于降低心脏瓣膜钙化进展和肾功能恶化的风险。