Aromatase Inhibitors and the Risk of Cardiovascular Outcomes in Women With Breast Cancer A Population-Based Cohort Study
Aromatase Inhibitors and the Risk of Cardiovascular Outcomes in Women With Breast Cancer A Population-Based Cohort Study
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DOI：
10.1161/circulationaha.119.044750
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发表时间：
2020-02-18
期刊：
影响因子：
37.8
通讯作者：
Azoulay, Laurent
中科院分区：
文献类型：
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作者：
Khosrow-Khavar, Farzin;Filion, Kristian B.;Azoulay, Laurent
背景：芳香酶抑制剂与女性乳腺癌患者心血管预后之间的关系存在争议。考虑到随机对照试验和观察性研究的不同发现，需要进行更多的研究来解决这一安全问题。方法：我们使用链接到医院流行病学统计和国家统计局数据库的英国临床实践研究数据链接进行了一项基于人群的队列研究。研究人群包括1998年4月1日至2016年2月29日期间新诊断为乳腺癌的女性，开始使用芳香酶抑制剂或他莫昔芬进行激素治疗。我们使用具有相反治疗概率和截尾加权的COX比例风险模型来估计风险比(HR)，其中95%的CI比较新使用芳香酶抑制剂和新使用他莫昔芬对每个研究结果(心肌梗死、缺血性中风、心力衰竭和心血管死亡率)的影响。结果：研究人群包括23525名新诊断为乳腺癌的患者，其中17922人开始接受芳香酶抑制剂或他莫昔芬治疗(分别为8139和9783人)。与使用他莫昔芬相比，芳香酶抑制剂的使用显著增加了心力衰竭的风险(每1000人年发生率5.4比1.8；心率1.86[95%可信区间1.14-3.03])和心血管死亡率(发病率9.5比4.7每1000人年；心率1.50[95%可信区间1.11-2.04])。芳香酶抑制剂与升高的HRs相关，但与包括零值的顺应性相关，心肌梗死(发生率，3.9比1.8/1000人年；HR，1.37[95%CI，0.88-2.13])和缺血性中风(发生率，5.6比3.2/1000人年；HR，1.19[95%CI，0.82-1.72])。结论：在这项基于人群的研究中，与他莫昔芬相比，芳香化酶抑制剂与心力衰竭和心血管死亡的风险增加有关。心肌梗死和缺血性中风的风险虽然不大，但也有增加的趋势。与他莫昔芬相比，芳香酶抑制剂增加心血管事件的风险应与其良好的临床益处相平衡。
Background:The association between aromatase inhibitors and cardiovascular outcomes among women with breast cancer is controversial. Given the discrepant findings from randomized controlled trials and observational studies, additional studies are needed to address this safety concern.Methods:We conducted a population-based cohort study using the UK Clinical Practice Research Datalink linked to the Hospital Episode Statistics and Office for National Statistics databases. The study population consisted of women newly diagnosed with breast cancer initiating hormonal therapy with aromatase inhibitors or tamoxifen between April 1, 1998, and February 29, 2016. We usedCox proportional hazards models with inverse probability of treatment and censoring weighting to estimate hazard ratios (HRs) with 95% CIs comparing new users of aromatase inhibitors with new users of tamoxifen for each of the study outcomes (myocardial infarction, ischemic stroke, heart failure, and cardiovascular mortality).Results:The study population consisted of 23 525 patients newly diagnosed with breast cancer, of whom 17 922 initiated treatment with either an aromatase inhibitor or tamoxifen (8139 and 9783, respectively). The use of aromatase inhibitors was associated with a significantly increased risk of heart failure (incidence rate, 5.4 versus 1.8 per 1000 person-years; HR, 1.86 [95% CI, 1.14-3.03]) and cardiovascular mortality (incidence rate, 9.5 versus 4.7 per 1000 person-years; HR, 1.50 [95% CI, 1.11-2.04]) compared with the use of tamoxifen. Aromatase inhibitors were associated with elevated HRs, but with CIs including the null value, for myocardial infarction (incidence rate, 3.9 versus 1.8 per 1000 person-years; HR, 1.37 [95% CI, 0.88-2.13]) and ischemic stroke (incidence rate, 5.6 versus 3.2 per 1000 person-years; HR, 1.19 [95% CI, 0.82-1.72]).Conclusions:In this population-based study, aromatase inhibitors were associated with increased risks of heart failure and cardiovascular mortality compared with tamoxifen. There were also trends toward increased risks, although nonsignificant, of myocardial infarction and ischemic stroke. The increased risk of cardiovascular events associated with aromatase inhibitors should be balanced with their favorable clinical benefits compared with tamoxifen.