Background

Breast cancer patients often receive cardiotoxic drugs such as anthracyclines (ANT) and Trastuzumab. Numerous trials have tested angiotensin converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), and beta-blockers (BB) as monotherapy or in combination to reprogram cardiac function dynamics in these patients, but no clear conclusions have been reached thus far, due to evident heterogeneity in the design of clinical studies.

Methods

This PRISMA-guided systematic review and meta-analysis assessed a pooled effect estimate of the potential benefit/harm of ACEi/ARB/BB in breast cancer patients treated with ANT ± Trastuzumab. The protocol was registered on the PROSPERO database. Electronic databases (PubMed, Cochrane Central, Scopus, Web of Science) were searched from inception until February 2019.

Results

Twenty-two prospective studies comprising of 2,302 participants were included in the meta-analysis. The 16 studies testing the protective effects of ACEi/ARB/BB after immediate completion of chemotherapy showed a significant lower difference in the mean change of left ventricular ejection fraction (LVEF) after chemotherapy completion in patiens receiving cardio-protective drugs as compared to controls, with a standardized mean difference [SMD = -2.36 (95% CI: -3.23 to -1.49), p < 0.00001] favoring the protective role of these drugs. LVEF was evaluated after 6 months after completion of chemotherapy in 3 studies, where ACEi/ARB/BB persistently showed cardio-protective effects as compared to controls [SMD = -6.54 (95% CI: -10.74 to -2.34), p = 0.002]. After 1 year from completion of chemotherapy, ACEi/ARB/BB preserved beneficial effects on LVEF vs control [SMD = -5.37 (95% CI: -9.31 to -1.43), p = 0.008]. The effect of ACEi/ARB/BB on end-systolic volume (ESV) and end-diastolic volume (EDV) were evaluated immediately after chemotherapy completion and after 1 year. No significant protective effect was apparent. On the other hand, end-diastolic diameter (EDD) was significantly spared in the ACEi/ARB/BB group vs control after chemotherapy completion [SMD = -1.11 (95% CI: -1.88 to -0.35), p = 0.004]. Heart failure as a clinical endpoint was assessed in 11 trials. The incidence of heart failure was significantly lower in the ACEi/ARB/BB group as compared to control [Odds ratio = 0.12 (95% CI: 0.03 to 0.45), p = 0.002].

Conclusion

ACEi/ARB/BB may act as cardioprotective agents in breast cancer patients who undergo ANT ± Trastuzumab. More studies are required to better assess the magnitude of the cardiotoxicity hazards of ANT ± Trastuzumab, with more precise assessment of the effect of ACEi/ARB/BB on cardio-protection.

中文翻译：

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心脏保护剂在接受蒽环类±曲妥珠单抗的乳腺癌患者心脏保护中的作用：临床研究的荟萃分析。

背景

乳腺癌患者经常接受心脏毒性药物，例如蒽环类药物（ANT）和曲妥珠单抗。许多试验已经测试了血管紧张素转化酶抑制剂（ACEi），血管紧张素受体阻滞剂（ARB）和β受体阻滞剂（BB）作为单一疗法或联合疗法对这些患者的心功能动力学进行重编程，但迄今为止尚未获得明确的结论，由于临床研究设计中明显的异质性。

方法

这项由PRISMA指导的系统评价和荟萃分析评估了ACEi / ARB / BB在接受ANT±曲妥珠单抗治疗的乳腺癌患者中的潜在获益/危害的综合影响评估。该协议已在PROSPERO数据库中注册。从开始到2019年2月，都搜索了电子数据库（PubMed，Cochrane Central，Scopus，Web of Science）。

结果

荟萃分析包括22项前瞻性研究，共2,302名参与者。接受ACEi / ARB / BB防护后立即进行化疗的16项研究显示，与对照组相比，接受心脏防护药物的患者化疗完成后左心室射血分数（LVEF）的平均变化显着较低，具有标准化的均值差[SMD = -2.36（95％CI：-3.23至-1.49），p <0.00001]，有利于这些药物的保护作用。在3个研究中，化疗完成后6个月后评估了LVEF，其中ACEi / ARB / BB与对照相比持续显示出心脏保护作用[SMD = -6.54（95％CI：-10.74至-2.34），p = 0.002 ]。化疗完成一年后，与对照相比，ACEi / ARB / BB保留了对LVEF的有益作用[SMD = -5.37（95％CI：-9.31至-1.43），p = 0.008]。化疗后立即和一年后评估ACEi / ARB / BB对收缩末期容积（ESV）和舒张末期容积（EDV）的影响。没有明显的保护作用。另一方面，ACEi / ARB / BB组的舒张末期直径（EDD）与化疗完成后的对照组相比没有明显差异[SMD = -1.11（95％CI：-1.88至-0.35），p = 0.004]。在11项试验中评估了心力衰竭作为临床终点。与对照组相比，ACEi / ARB / BB组的心力衰竭发生率明显更低[几率= 0.12（95％CI：0.03至0.45），p = 0.002]。化疗后立即和一年后评估ACEi / ARB / BB对收缩末期容积（ESV）和舒张末期容积（EDV）的影响。没有明显的保护作用。另一方面，ACEi / ARB / BB组的舒张末期直径（EDD）与化疗完成后的对照组相比没有明显差异[SMD = -1.11（95％CI：-1.88至-0.35），p = 0.004]。在11项试验中评估了心力衰竭作为临床终点。与对照组相比，ACEi / ARB / BB组的心力衰竭发生率明显更低[几率= 0.12（95％CI：0.03至0.45），p = 0.002]。化疗后立即和一年后评估ACEi / ARB / BB对收缩末期容积（ESV）和舒张末期容积（EDV）的影响。没有明显的保护作用。另一方面，ACEi / ARB / BB组的舒张末期直径（EDD）与化疗完成后的对照组相比没有明显差异[SMD = -1.11（95％CI：-1.88至-0.35），p = 0.004]。在11项试验中评估了心力衰竭作为临床终点。与对照组相比，ACEi / ARB / BB组的心力衰竭发生率明显更低[几率= 0.12（95％CI：0.03至0.45），p = 0.002]。化疗完成后，ACEi / ARB / BB组与对照组相比，舒张末期舒张末期直径（EDD）明显较对照组[SMD = -1.11（95％CI：-1.88至-0.35），p = 0.004]。在11项试验中评估了心力衰竭作为临床终点。与对照组相比，ACEi / ARB / BB组的心力衰竭发生率明显更低[几率= 0.12（95％CI：0.03至0.45），p = 0.002]。化疗完成后，ACEi / ARB / BB组与对照组相比，舒张末期舒张末期直径（EDD）明显较对照组[SMD = -1.11（95％CI：-1.88至-0.35），p = 0.004]。在11项试验中评估了心力衰竭作为临床终点。与对照组相比，ACEi / ARB / BB组的心力衰竭发生率明显更低[几率= 0.12（95％CI：0.03至0.45），p = 0.002]。

结论

ACEi / ARB / BB可能在接受ANT±曲妥珠单抗的乳腺癌患者中充当心脏保护剂。需要进行更多的研究以更好地评估ANT±曲妥珠单抗的心脏毒性危害的程度，并更精确地评​​估ACEi / ARB / BB对心脏保护的作用。