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Abstract：
OBJECTIVE: The aim of the present study was to analyse concomitant drug use and its association with outcome in patients (N = 17 701) receiving rivaroxaban or standard of care (SOC) for the prevention of venous thromboembolism after major orthopaedic surgery in the non-interventional, phase IV XAMOS (Xarelto® in the prophylaxis of post-surgical venous thromboembolism after elective major orthopaedic surgery of hip or knee) study.
METHODS: Concomitant drug use was at the discretion of the treating physician. Prespecified co-medications of interest were cytochrome P450 (CYP) 3A4/P-glycoprotein inhibitors/inducers, platelet aggregation inhibitors (PAIs) and nonsteroidal anti-inflammatory drugs (NSAIDs). Crude event incidences were compared between rivaroxaban and SOC groups.
RESULTS: CYP3A4/P-glycoprotein inhibitor/inducer use was infrequent, in contrast to PAI (~7%) and NSAID (~52%) use. Rivaroxaban was associated with a lower incidence of overall symptomatic thromboembolic events compared with SOC, regardless of co-medication use. In both treatment groups, PAI users, with higher age and prevalence of cardiovascular co-morbidities, had similar higher (>7-fold) incidences of symptomatic arterial but not venous thromboembolic events compared with non-users. NSAID use had no influence on thromboembolic events. However, odds ratios (ORs) for major bleeding events (European Medicines Agency definition) were higher in NSAID users compared with non-users in rivaroxaban [OR = 1.50; 95% confidence interval (CI) 1.06, 2.13] and SOC (OR = 1.70; CI 1.16, 2.49) groups. In PAI users, ORs for major bleeding events were no different from those of non-users in both the rivaroxaban (OR = 1.49; CI 0.84, 2.65) and SOC (OR = 1.46; CI 0.82, 2.62) groups.
CONCLUSIONS: Use of NSAIDs in XAMOS was frequent and associated with a higher frequency of bleeding events in patients receiving rivaroxaban or SOC, although the benefit-risk profile of rivaroxaban compared with SOC was maintained.
METHODS: Concomitant drug use was at the discretion of the treating physician. Prespecified co-medications of interest were cytochrome P450 (CYP) 3A4/P-glycoprotein inhibitors/inducers, platelet aggregation inhibitors (PAIs) and nonsteroidal anti-inflammatory drugs (NSAIDs). Crude event incidences were compared between rivaroxaban and SOC groups.
RESULTS: CYP3A4/P-glycoprotein inhibitor/inducer use was infrequent, in contrast to PAI (~7%) and NSAID (~52%) use. Rivaroxaban was associated with a lower incidence of overall symptomatic thromboembolic events compared with SOC, regardless of co-medication use. In both treatment groups, PAI users, with higher age and prevalence of cardiovascular co-morbidities, had similar higher (>7-fold) incidences of symptomatic arterial but not venous thromboembolic events compared with non-users. NSAID use had no influence on thromboembolic events. However, odds ratios (ORs) for major bleeding events (European Medicines Agency definition) were higher in NSAID users compared with non-users in rivaroxaban [OR = 1.50; 95% confidence interval (CI) 1.06, 2.13] and SOC (OR = 1.70; CI 1.16, 2.49) groups. In PAI users, ORs for major bleeding events were no different from those of non-users in both the rivaroxaban (OR = 1.49; CI 0.84, 2.65) and SOC (OR = 1.46; CI 0.82, 2.62) groups.
CONCLUSIONS: Use of NSAIDs in XAMOS was frequent and associated with a higher frequency of bleeding events in patients receiving rivaroxaban or SOC, although the benefit-risk profile of rivaroxaban compared with SOC was maintained.
摘要：
目的：本研究的目的是分析非介入性骨科大手术后接受利伐沙班或标准治疗（SOC）预防静脉血栓栓塞的患者（N=17.701）的合并用药及其与预后的关系。IV期XAMOS（Xarelto®预防择期髋关节或膝关节大型骨科手术后静脉血栓栓塞）研究。
方法：合并用药由主治医师自行决定。预先指定的目标共同药物是细胞色素P450（CYP）3A4/P-糖蛋白抑制剂/诱导剂，血小板聚集抑制剂（PAIs）和非甾体抗炎药（NSAIDs）。比较利伐沙班组和SOC组之间的粗事件发生率。
结果：CYP3A4/P-糖蛋白抑制剂/诱导剂的使用很少，与PAI(~7%)和NSAID(~52%)的使用相反。与SOC相比，利伐沙班的总体症状性血栓栓塞事件发生率较低，无论共同用药。在两个治疗组中，PAI用户,随着年龄和心血管合并症患病率的增加，与非使用者相比,有症状的动脉血栓栓塞事件的发生率相似(>7倍),但静脉血栓栓塞事件的发生率没有增加.使用NSAID对血栓栓塞事件没有影响。然而,在利伐沙班组中,非甾体抗炎药组(OR=1.50;95%置信区间(CI)1.06,2.13]和SOC(OR=1.70;CI1.16,2.49)相比,非甾体抗炎药组(欧洲药品管理局定义)中大出血事件的比值比(OR=1.16,2.49)更高.在PAI用户中，在利伐沙班（OR=1.49；CI0.84，2.65）和SOC（OR=1.46；CI0.82，2.62）组中，主要出血事件的OR值与非使用者无差异。
结论：在接受利伐沙班或SOC的患者中，在XAMOS中使用非甾体抗炎药是频繁的，并且与更高的出血事件频率相关。尽管利伐沙班与SOC相比的获益-风险特征得以维持.
方法：合并用药由主治医师自行决定。预先指定的目标共同药物是细胞色素P450（CYP）3A4/P-糖蛋白抑制剂/诱导剂，血小板聚集抑制剂（PAIs）和非甾体抗炎药（NSAIDs）。比较利伐沙班组和SOC组之间的粗事件发生率。
结果：CYP3A4/P-糖蛋白抑制剂/诱导剂的使用很少，与PAI(~7%)和NSAID(~52%)的使用相反。与SOC相比，利伐沙班的总体症状性血栓栓塞事件发生率较低，无论共同用药。在两个治疗组中，PAI用户,随着年龄和心血管合并症患病率的增加，与非使用者相比,有症状的动脉血栓栓塞事件的发生率相似(>7倍),但静脉血栓栓塞事件的发生率没有增加.使用NSAID对血栓栓塞事件没有影响。然而,在利伐沙班组中,非甾体抗炎药组(OR=1.50;95%置信区间(CI)1.06,2.13]和SOC(OR=1.70;CI1.16,2.49)相比,非甾体抗炎药组(欧洲药品管理局定义)中大出血事件的比值比(OR=1.16,2.49)更高.在PAI用户中，在利伐沙班（OR=1.49；CI0.84，2.65）和SOC（OR=1.46；CI0.82，2.62）组中，主要出血事件的OR值与非使用者无差异。
结论：在接受利伐沙班或SOC的患者中，在XAMOS中使用非甾体抗炎药是频繁的，并且与更高的出血事件频率相关。尽管利伐沙班与SOC相比的获益-风险特征得以维持.
