Do adjuvant aromatase inhibitors increase the cardiovascular risk in postmenopausal women with early breast cancer? Meta-analysis of randomized trials
Do adjuvant aromatase inhibitors increase the cardiovascular risk in postmenopausal women with early breast cancer? Meta-analysis of randomized trials
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DOI：
10.1002/cncr.23171
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发表时间：
2008-01-15
期刊：
影响因子：
6.2
通讯作者：
Giannarelli, Diana
中科院分区：
文献类型：
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作者：
Cuppone, Federica;Bria, Emilio;Giannarelli, Diana
背景尽管使用芳香酶抑制剂（AIs）与他莫昔芬相比对于早期乳腺癌具有优势，但证实了出乎意料的更多数量的3级和4级心血管事件（CVAE）（如由加拿大国家癌症研究所-常见毒性标准[版本2.0]定义的）。比较At与他莫昔芬治疗早期乳腺癌的3期随机临床试验（RCT）被认为符合本综述的条件。推导出基于事件的风险比（RR）及其95%置信区间（95%CI），并进行异质性检验。最后，确定事件发生率的绝对差异（AD）和伤害1例患者所需的患者数量（NNH）。7项合格RCT（19，818例患者）报告了CVAE结果。当考虑所有RCT时，两组之间主要终点（CVAE）的AD（0.52%），他莫昔芬与AI相比具有统计学显著性（RR，1.31; 95% CI，1.07-1.60; P = 0.007）。这转化为189例患者的NNH值;当仅考虑第三代AI时，差异（0.57%）仍然显著（RR，1.34; 95% CI，1.09-1.63; P = 0.0038）。无论采用何种治疗策略，他莫昔芬组血栓栓塞事件发生率明显更高（RR，0.53; 95%CI，0.42-0.65; P <0.0001），无显著异质性（P = 0.21）。AD为1.17%，NNH值为85例。根据该荟萃分析的结果，接受AI的患者发生3级和4级CVAE的风险高于接受他莫昔芬的患者，差异具有统计学意义。然而，AD相对较低，160 - 180例患者必须接受治疗才能发生1起事件。
BACKGROUND. Despite the advantages from using aromatase inhibitors (AIs) compared with tamoxifen for early breast cancer, an unexpectedly greater number of grade 3 and 4 cardiovascular events (CVAE) (as defined by National Cancer Institute of Canada-Common Toxicity Criteria [version 2.0] was demonstrated.METHODS. Phase 3 randomized clinical trials (RCTs) comparing At with tamoxifen in early breast cancer were considered eligible for this review. The event-based risk ratios (RRs) with 95% confidence intervals (95% CIs) were derived, and a test of heterogeneity was applied. Finally, absolute differences (ADs) in event rates and the number of patients needed to harm 1 patient (NNH) were determined.RESULTS. Seven eligible RCTs (19,818 patients) reported CVAE results. When considering all RCTs, the AD of the primary endpoint (CVAE) between the 2 arms (0.52%), tamoxifen versus AI, was statistically significant (RR, 1.31; 95% CI, 1.07-1.60; P = .007). This translated into an NNH value of 189 patients; when only third-generation AIs were considered, the difference (0.57%) remained significant (RR, 1.34; 95% CI, 1.09-1.63; P = .0038). Thromboembolic events were significantly more frequent in the tamoxifen arm, regardless of the strategy adopted (RR, 0.53; 95% CI, 0.42-0.65; P < .0001), without significant heterogeneity (P = .21). An AD of 1.17% and an NNH value of 85 patients were observed.CONCLUSIONS. According to the results from this meta-analysis, the risk of grade 3 and 4 CVAEs in patients who were receiving AIs was higher compared with the risk in patients who were receiving tamoxifen, and the difference reached statistical significance. However, the AD was relatively low, and from 160 to 180 patients had to be treated to produce 1 event.