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在非转移性乳腺癌辅助曲妥珠单抗化疗期间使用血管紧张素转换酶抑制剂和β受体阻滞剂:现实世界中的风险标志物还是心脏保护剂?

Administration of angiotensin-converting enzyme inhibitors and β-blockers during adjuvant trastuzumab chemotherapy for nonmetastatic breast cancer: marker of risk or cardioprotection in the real world?

机构信息

National Cancer Institute Giovanni Paolo II of Bari, Viale Orazio Flacco 36, Bari, Italy.

出版信息

Oncologist. 2012;17(7):917-24. doi: 10.1634/theoncologist.2011-0445. Epub 2012 Jun 6.

DOI:10.1634/theoncologist.2011-0445
PMID:22673631
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3399646/
Abstract

BACKGROUND

Adjuvant trastuzumab therapy improves the outcome of patients with early breast cancer (EBC) and overexpression of human epidermal growth factor receptor 2 (HER2). However, it is potentially cardiotoxic. This study aims to evaluate the relationship between the use of angiotensin-converting enzyme inhibitors/receptor blockers (ACEi/ARBs) and/or β-blockers and development of heart failure (HF) and/or left ventricular dysfunction during 1 year of adjuvant trastuzumab therapy.

METHODS

A total of 499 women receiving adjuvant trastuzumab therapy for EBC entered in a multicenter registry and were divided into four subgroups according to treatment with ACEi/ARBs and/or β-blockers. Occurrence of HF and decrease of left ventricular ejection fraction (LVEF; minimum 10 percentage points) were recorded.

RESULTS

HF occurred in 2% of patients who did not take either ACEi/ARBs or β-blockers, 8% of patients receiving ACEi/ARBs alone, 8% receiving β-blockers alone (p = .03), and 19% receiving both medications (p < .01). The prevalence of patients with LVEF that decreased by at least 10 percentage points was similar in all groups. Combined ACEi/ARBs and β-blocker therapy was independently associated with hypertension and a significant reduction of LVEF from baseline to 3-month evaluation. The use of ACEi/ARBs alone or β-blockers alone was predicted only by hypertension. Combined therapy of ACEi/ARBs plus β-blockers predicted LVEF recovery from the 3-month to 12-month evaluation.

CONCLUSIONS

In clinical practice, the degree of hypertension and decrease in LVEF during the first 3 months of adjuvant trastuzumab therapy for EBC are associated with the use of ACEi/ARBs and β-blockers. The combined use of these two medications is associated with a recovery of LVEF during months 3-12 of adjuvant trastuzumab therapy.

摘要

背景

曲妥珠单抗辅助治疗可改善人表皮生长因子受体 2(HER2)过表达的早期乳腺癌(EBC)患者的预后。然而,它具有潜在的心脏毒性。本研究旨在评估血管紧张素转换酶抑制剂/受体阻滞剂(ACEi/ARBs)和/或β受体阻滞剂的使用与曲妥珠单抗辅助治疗 1 年内心力衰竭(HF)和/或左心室功能障碍的发展之间的关系。

方法

共 499 例接受 EBC 曲妥珠单抗辅助治疗的女性入组多中心登记研究,并根据 ACEi/ARBs 和/或β受体阻滞剂的治疗情况分为四组。记录 HF 的发生和左心室射血分数(LVEF;至少降低 10%)的降低情况。

结果

未使用 ACEi/ARBs 或β受体阻滞剂的患者中 HF 的发生率为 2%,单独使用 ACEi/ARBs 的患者发生率为 8%,单独使用β受体阻滞剂的患者发生率为 8%(p=.03),联合使用两种药物的患者发生率为 19%(p <.01)。所有组中 LVEF 至少降低 10%的患者比例相似。联合 ACEi/ARBs 和β受体阻滞剂治疗与高血压和基线至 3 个月评估时 LVEF 的显著降低独立相关。ACEi/ARBs 单独或β受体阻滞剂单独使用仅预测高血压。ACEi/ARBs 联合β受体阻滞剂的单独治疗预测了从 3 个月到 12 个月评估时 LVEF 的恢复。

结论

在 EBC 曲妥珠单抗辅助治疗的前 3 个月,高血压的严重程度和 LVEF 的降低与 ACEi/ARBs 和β受体阻滞剂的使用相关。这两种药物的联合使用与曲妥珠单抗辅助治疗后 3-12 个月期间 LVEF 的恢复相关。

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