Abstract：
OBJECTIVE: Trastuzumab, a potent anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibody, is conditionally reimbursed by the Taiwan National Health Insurance (NHI) for HER2-positive breast cancer (BC). Trastuzumab-induced cardiotoxicity studies have well characterized heart failure (HF) but fewer addressed arrhythmia, particularly the association of potential life threatening atrial fibrillation (Af) is poorly characterized. We aimed to study the trastuzumab-related risk of Af and HF using the claimed data of Taiwan NHI.
METHODS: A nationwide retrospective cohort of patients with BC from the Taiwan NHI reimbursement database from January 2007 to December 2016 was analyzed. Propensity score matching and competing risk model analysis were used for adjusting confounding concurrent medication or comorbidities and competing events. The HF study was used to validate the method used.
RESULTS: For Af, 12,472 trastuzumab users were matched with 12,472 non-trastuzumab users. For HF, 12,241 trastuzumab users and 12,241 non-users were enrolled. We found that trastuzumab users had significantly worse HF-free survival but not Af-free survival than non-trastuzumab users. In the competing risk analysis, the use of trastuzumab did not increase the risk of Af (hazard ratio [HR] 0.76, P = 0.0006) but was associated with HF (HR 1.19, P = 0.0052). The risk trends among stratifications by comorbidities and concurrent medication remained in similar directions for both Af and HF.
CONCLUSIONS: Trastuzumab in real-world practice was associated with an increased risk of HF, but was not associated with an increased risk of Af in BC patients. Trastuzumab-induced arrhythmogenic effects may be masked by concurrent heart-protecting measures, more prominent roles of comorbidities or concurrent medications under real-world settings. Further studies are required.
METHODS: A nationwide retrospective cohort of patients with BC from the Taiwan NHI reimbursement database from January 2007 to December 2016 was analyzed. Propensity score matching and competing risk model analysis were used for adjusting confounding concurrent medication or comorbidities and competing events. The HF study was used to validate the method used.
RESULTS: For Af, 12,472 trastuzumab users were matched with 12,472 non-trastuzumab users. For HF, 12,241 trastuzumab users and 12,241 non-users were enrolled. We found that trastuzumab users had significantly worse HF-free survival but not Af-free survival than non-trastuzumab users. In the competing risk analysis, the use of trastuzumab did not increase the risk of Af (hazard ratio [HR] 0.76, P = 0.0006) but was associated with HF (HR 1.19, P = 0.0052). The risk trends among stratifications by comorbidities and concurrent medication remained in similar directions for both Af and HF.
CONCLUSIONS: Trastuzumab in real-world practice was associated with an increased risk of HF, but was not associated with an increased risk of Af in BC patients. Trastuzumab-induced arrhythmogenic effects may be masked by concurrent heart-protecting measures, more prominent roles of comorbidities or concurrent medications under real-world settings. Further studies are required.
摘要：
目标：曲妥珠单抗，一种有效的抗人表皮生长因子受体2（HER2）单克隆抗体，由台湾国民健康保险（NHI）有条件地报销HER2阳性乳腺癌（BC）。曲妥珠单抗诱导的心脏毒性研究具有明确的心力衰竭（HF）特征，但解决的心律失常较少，尤其是潜在的危及生命的心房颤动(Af)的相关性缺乏表征.我们旨在使用台湾NHI声称的数据研究曲妥珠单抗相关的Af和HF风险。
方法：分析了2007年1月至2016年12月台湾NHI报销数据库中BC患者的全国回顾性队列。倾向评分匹配和竞争风险模型分析用于调整混杂并发药物或合并症和竞争事件。使用HF研究来验证所使用的方法。
结果：对于Af，12,472名曲妥珠单抗用户与12,472名非曲妥珠单抗用户匹配。对于HF，12,241名曲妥珠单抗用户和12,241名非用户登记。我们发现，与非曲妥珠单抗使用者相比，曲妥珠单抗使用者的无HF生存率明显较差，但无Af生存率不高。在竞争风险分析中，曲妥珠单抗的使用并未增加Af的风险(风险比[HR]0.76,P=0.0006),但与HF相关(HR1.19,P=0.0052).Af和HF的合并症和并发药物的分层风险趋势保持相似。
结论：曲妥珠单抗在现实世界实践中与HF风险增加相关，但与BC患者Af风险增加无关.曲妥珠单抗诱导的心律失常效应可能被同时的心脏保护措施掩盖。在现实世界中，合并症或并发药物的作用更为突出。需要进一步的研究。
方法：分析了2007年1月至2016年12月台湾NHI报销数据库中BC患者的全国回顾性队列。倾向评分匹配和竞争风险模型分析用于调整混杂并发药物或合并症和竞争事件。使用HF研究来验证所使用的方法。
结果：对于Af，12,472名曲妥珠单抗用户与12,472名非曲妥珠单抗用户匹配。对于HF，12,241名曲妥珠单抗用户和12,241名非用户登记。我们发现，与非曲妥珠单抗使用者相比，曲妥珠单抗使用者的无HF生存率明显较差，但无Af生存率不高。在竞争风险分析中，曲妥珠单抗的使用并未增加Af的风险(风险比[HR]0.76,P=0.0006),但与HF相关(HR1.19,P=0.0052).Af和HF的合并症和并发药物的分层风险趋势保持相似。
结论：曲妥珠单抗在现实世界实践中与HF风险增加相关，但与BC患者Af风险增加无关.曲妥珠单抗诱导的心律失常效应可能被同时的心脏保护措施掩盖。在现实世界中，合并症或并发药物的作用更为突出。需要进一步的研究。
