Ⅹa因子抑制剂与心血管药物的相互作用

Interactions between factor Ⅹa inhibitors and cardiovascular drugs

新型口服抗凝药(NOACs)Ⅹa因子抑制剂主要通过抑制凝血酶瀑布过程中Ⅹa因子而发挥抗凝作用,已被批准用于非瓣膜性心房颤动患者的卒中预防及其他血栓栓塞性疾病。Ⅹa因子抑制剂为P糖蛋白(P-gp)底物,且部分经细胞色素P450(CYP450)酶代谢。大型临床研究及个案报道发现Ⅹa因子抑制剂与某些心血管药物联用后可影响Ⅹa因子抑制剂药动学参数,继而影响临床疗效和安全性。抗心律失常药物胺碘酮、决奈达隆、奎尼丁及钙通道阻滞药如维拉帕米和地尔硫可导致Ⅹa因子抑制剂暴露量增加,抗血小板药物可与Ⅹa因子抑制剂产生药效学相互作用,均会导致潜在出血风险增加;硝苯地平、地高辛及阿托伐他汀与Ⅹa因子抑制剂相互作用无临床意义。临床应根据患者肝、肾功能,病理状态及具体联合药物的情况采取调整Ⅹa因子抑制剂剂量、更换药物或密切监测等措施。

New oral anticoagulant(NOACs) factor Ⅹa inhibitors exert anticoagulant effects mainly by inhibiting factor Ⅹa in the process of thrombin falls, and have been widely used in stroke prevention of thromboembolic disease and non-valvular atrial fibrillation. Factor Ⅹa inhibitors are P-glycoprotein(P-gp) substrates and partially metabolized by cytochrome P450(CYP450) enzymes. However, many common cardiovascular drugs can affect the activity of P-gp or CYP450, thus change the pharmacokinetics of factor Ⅹa inhibitors and affect their anticoagulant efficacy. Large clinical studies and case reports have found that fact or Ⅹa inhibitors combined with some cardiovascular drugs can affect the pharmacokinetic parameters of fact or Ⅹa inhibitors, and then affect the clinical efficacy and safety. Antiarrhythmic drugs amiodarone, dinedarone, quinidine and calcium channel blockers such as verapamil and diltiazem can increase the exposure of factor Ⅹa inhibitors and antiplatelet drugs can interact with factor Ⅹa inhibitors, resulting in an increased risk of potential bleeding, while nifedipine, digoxin and atorvastatin have no clinical significance. Clinically, it is necessary to adjust the dosage of factor Ⅹa inhibitors, change drugs or closely monitor according to the patients’ liver and kidney function, pathological status and specific combined drugs.