非维生素K拮抗剂口服抗凝剂(NOAC)由P-糖蛋白(P-gp)分泌,一些由CYP450酶如CYP3A4代谢。尽管NOAC存在较少的药物相互作用,目前尚不清楚在使用药代动力学相互作用药物的房颤(AF)患者中,NOAC是否也应优于维生素K拮抗剂(VKAs).因此,在接受P-gp和/或CYP450相互作用药物治疗的AF患者中,研究了NOACs与VKAs的获益-风险特征.
使用PubMed和Embase,纳入了使用P-gp和/或CYP450相互作用药物的AF患者中NOAC与VKAs的有效性和安全性的随机对照试验和观察性研究.进行了荟萃分析,用Mantel-Haenszel方法计算相对风险(RR)和95%置信区间(CI)。
纳入了12项研究,调查使用P-gp/CYP3A4抑制剂治疗的10,793NOAC和10,096VKA使用者,而未发现有关P-gp和/或CYP450诱导药物的研究。与VKAs相比,NOAC与临界非显著降低卒中或全身性栓塞(卒中/SE)风险相关(RR0.85,95CI(0.72-1.01)),显著降低颅内出血(RR0.47,95CI(0.34-0.65))和全因死亡风险(RR0.87,95CI(0.79-0.95),但消化道出血风险显著升高(RR1.74,95CI(1.06-2.86))。在使用胺碘酮的房颤患者中,NOAC与显著降低卒中/SE(RR0.71,95CI(0.54-0.93))和颅内出血风险(RR0.51,95CI(0.29-0.88))相关,但消化道出血风险(RR2.15,95CI(1.24-3.72))明显高于VKAs。
在使用P-gp/CYP3A4抑制剂的AF患者中,与VKAs相比,NOAC的获益-风险特征得以保留。包括胺碘酮.
Non-vitamin K antagonist oral anticoagulants (NOACs) are excreted by P-glycoprotein (P-gp) and some are metabolized by CYP450 enzymes such as CYP3A4. Although fewer drug interactions are present with NOACs, it is unclear whether NOACs should also be preferred over vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) using pharmacokinetically interacting drugs. Therefore, the benefit-risk profile of NOACs versus VKAs was investigated in AF patients treated with P-gp and/or CYP450-interacting drugs.
Using PubMed and Embase, randomized controlled trials and observational studies on the effectiveness and safety of NOACs versus VKAs in AF patients using P-gp and/or CYP450-interacting drugs were included. A meta-analysis was performed, calculating relative risks (RR) and 95% confidence intervals (CI) with the Mantel-Haenszel method.
Twelve studies were included, investigating 10,793
NOAC and 10,096 VKA users treated with P-gp/CYP3A4 inhibitors, whereas no studies on P-gp and/or CYP450-inducing drugs were identified. Compared to VKAs, NOACs were associated with a borderline non-significantly lower stroke or systemic embolism (stroke/SE) risk (RR 0.85, 95%CI (0.72-1.01)), significantly lower intracranial bleeding (RR 0.47, 95%CI (0.34-0.65)) and all-cause mortality risks (RR 0.87, 95%CI (0.79-0.95), but significantly higher gastrointestinal bleeding risk (RR 1.74, 95%CI (1.06-2.86)). Among AF patients using amiodarone, NOACs were associated with significantly lower stroke/SE (RR 0.71, 95%CI (0.54-0.93)) and intracranial bleeding risks (RR 0.51, 95%CI (0.29-0.88)), but significantly higher gastrointestinal bleeding risk (RR 2.15, 95%CI (1.24-3.72)) than VKAs.
The benefit-risk profile of NOACs compared to VKAs was preserved in AF patients using P-gp/CYP3A4 inhibitors, including amiodarone.