Cardioprotective Effect of Statins in Patients With HER2-Positive Breast Cancer Receiving Trastuzumab Therapy
Cardioprotective Effect of Statins in Patients With HER2-Positive Breast Cancer Receiving Trastuzumab Therapy
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DOI：
10.1016/j.cjca.2018.11.028
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发表时间：
2019-02-01
影响因子：
6.2
通讯作者：
Thavendiranathan, Paaladinesh
中科院分区：
文献类型：
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作者：
Calvillo-Arguelles, Oscar;Abdel-Qadir, Husam;Thavendiranathan, Paaladinesh
背景：他汀类药物可以降低蒽环类药物所致心脏毒性的风险。在接受曲妥珠单抗治疗的患者中是否可以看到这样的心脏保护作用还没有被探索。方法：对连续接受曲妥珠单抗联合或不联合使用蒽环类药物的HER2+乳腺癌患者进行回顾性研究。在癌症治疗前和治疗期间接受他汀类药物治疗的患者与2名年龄相同(+/-2岁)、具有蒽环类药物暴露状态但未接受他汀类药物治疗的患者相匹配。主要结果是最终的左心室射血分数(LVEF)。使用协方差分析(ANCOVA)评估他汀类药物暴露与最终左心室射血分数之间的关系。建立Logistic回归模型来评估他汀类药物暴露与心脏毒性(次要结果)的关系。结果：129例患者(62+/-9岁)。43名患者在癌症治疗期间接受了他汀类药物治疗。曲妥珠单抗暴露时间的中位数为11.8(四分位数范围[IQR]11至12个月)。72名患者(56%)接受了蒽环类药物治疗。与对照组相比，服用他汀类药物的患者更容易发生糖尿病(37.2%比4.7%，P<；0.001)、高血压(58.1%比22.1%，P<；0.001)和冠心病(11.6%比2.3%，P=0.001)。在中位心脏随访时间11个月(IQR9~18)内，对照组调整后的最终左心室射血分数较低(61.2%vs64.6%，P=0.034)。对照组左心室射血分数变化显著(中位数-6%，IQR-10%至-1%P&0.001)，而他汀组则无明显变化(中位数0%，IQR-5%至+3%，P=0.27)。经校正分析，他汀类药物治疗与较低的心脏毒性风险独立相关(优势比[OR]0.32，95%可信区间[CI]，0.10-0.99，P=0.049)。结论：在接受曲妥珠单抗联合或不联合使用他汀类药物的乳腺癌患者中，联合使用他汀类药物与较低的心脏毒性风险相关。
Background: Statins can reduce the risk of anthracycline-induced cardiotoxicity. Whether such cardioprotective effects can be seen in trastuzumab-treated patients has not been explored.Methods: Consecutive women with HER2+ breast cancer who received trastuzumab with or without anthracyclines were identified retrospectively. Patients receiving statins before and during cancer treatment were matched with 2 patients of the same age (+/- 2 years) and anthracycline exposure status but without statin treatment. The primary outcome was final left ventricular ejection fraction (LVEF). Analysis of covariance (ANCOVA) was used to assess the relationship between statin exposure and the final LVEF. A logistic regression model was constructed to assess the relationship between statin exposure and cardiotoxicity (secondary outcome).Results: Included were 129 patients (62 +/- 9 years). Forty-three received statins during cancer treatment. The median trastuzumab exposure time was 11.8 (interquartile range [IQR] 11 to 12) months. Seventy-two (56%) patients received anthracyclines. Compared with controls, patients treated with statins were more likely to have diabetes (37.2% vs 4.7%, P < 0.001), hypertension (58.1% vs 22.1%, P < 0.001), and coronary artery disease (11.6% vs 2.3%, P = 0.04). Within a median cardiac follow-up duration of 11 (IQR 9 to 18) months, the adjusted final LVEF was lower in the control group (61.2% vs 64.6%, P = 0.034). A significant change in LVEF was observed in the control group (median -6%, IQR -10% to -1% P < 0.001) but not in the statin group (median 0%, IQR -5% to +3%, P = 0.27). Upon adjusted analysis, statin treatment was independently associated with a lower risk of cardiotoxicity (odds ratio [OR] 0.32, 95% confidence interval [CI], 0.10-0.99, P = 0.049).Conclusions: In women with HER2+ breast cancer receiving trastuzumab-based therapy with or without anthracyclines, concomitant use of statins was associated with a lower risk of cardiotoxicity.