University of Washington School of Nursing, Seattle, Washington, USA.
Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, Washington, USA.
Oncologist. 2020 Aug;25(8):712-721. doi: 10.1634/theoncologist.2019-0977. Epub 2020 Apr 6.
Recent clinical trials have evaluated angiotensin-converting enzyme (ACE) inhibitors (ACEis), angiotensin receptor blockers (ARBs), and beta blockers (BBs) in relation to cardiotoxicity in patients with cancer, typically defined by ejection fraction declines. However, these trials have not examined long-term, hard clinical endpoints. Within a prospective study, we examined the risk of heart failure (HF) and coronary heart disease (CHD) events in relation to use of commonly used antihypertensive medications, including ACEis/ARBs, BBs, calcium channel blockers (CCB), and diuretics, comparing women with and without cancer.
In a cohort of 56,997 Women's Health Initiative study participants free of cardiovascular disease who received antihypertensive treatment, we used multivariable-adjusted Cox regression models to calculate the hazard ratios (HRs) of developing CHD, HF, and a composite outcome of cardiac events (combining CHD and HF) in relation to use of ACEis/ARBs, CCBs, or diuretics versus BBs, separately in women with and without cancer.
Whereas there was no difference in risk of cardiac events comparing ACEi/ARB with BB use among cancer-free women (HR = 0.99 [0.88-1.12]), among cancer survivors ACEi/ARB users were at a 2.24-fold risk of total cardiac events (1.18-4.24); p-interaction = .06). When investigated in relation to CHD only, an increased risk was similarly observed in ACEi/ARB versus BB use for cancer survivors (HR = 1.87 [0.88-3.95]) but not in cancer-free women (HR = 0.91 [0.79-1.06]; p-interaction = .04). A similar pattern was also seen in relation to HF but did not reach statistical significance (p-interaction = .23).
These results from this observational study suggest differing risks of cardiac events in relation to antihypertensive medications depending on history of cancer. Although these results require replication before becoming actionable in a clinical setting, they suggest the need for more rigorous examination of the effect of antihypertensive choice on long-term cardiac outcomes in cancer survivors.
Although additional research is needed to replicate these findings, these data from a large, nationally representative sample of postmenopausal women indicate that beta blockers are favorable to angiotensin-converting enzyme inhibitors in reducing the risk of cardiac events among cancer survivors. This differs from the patterns observed in a noncancer cohort, which largely mirrors what is found in the randomized clinical trials in the general population.
最近的临床试验评估了血管紧张素转换酶（ACE）抑制剂（ACEi）、血管紧张素受体阻滞剂（ARB）和β受体阻滞剂（BB）在癌症患者中的心脏毒性，通常以射血分数下降来定义。然而，这些试验并未检查长期的、严重的临床终点。在一项前瞻性研究中，我们研究了在使用常用降压药物（包括 ACEi/ARB、BB、钙通道阻滞剂（CCB）和利尿剂）时，与无癌症的女性相比，癌症患者发生心力衰竭（HF）和冠心病（CHD）事件的风险。
在 56997 名无心血管疾病的妇女健康倡议研究参与者中，我们使用多变量调整的 Cox 回归模型，计算了在癌症患者和无癌症患者中，与 BB 相比，使用 ACEi/ARB、CCB 或利尿剂与 HF、CHD 和心脏事件（包括 CHD 和 HF）的复合终点的风险比（HR）。
在无癌症的女性中，ACEi/ARB 与 BB 相比，心脏事件的风险无差异（HR=0.99 [0.88-1.12]）；然而，在癌症幸存者中，ACEi/ARB 使用者的总心脏事件风险高 2.24 倍（1.18-4.24）；p 交互=.06）。当仅研究 CHD 时，在 ACEi/ARB 与 BB 相比，癌症幸存者的风险也增加（HR=1.87 [0.88-3.95]），但在无癌症的女性中无差异（HR=0.91 [0.79-1.06]；p 交互=.04）。在 HF 方面也观察到类似的模式，但未达到统计学意义（p 交互=.23）。
这些来自观察性研究的结果表明，根据癌症病史，不同的降压药物与心脏事件的风险有关。尽管这些结果在临床实践中具有可操作性之前需要复制，但它们表明需要更严格地检查降压药物选择对癌症幸存者长期心脏结局的影响。
尽管需要更多的研究来复制这些发现，但这些来自绝经后女性的大型、全国代表性样本的数据表明，β受体阻滞剂在降低癌症幸存者心脏事件风险方面优于 ACEi。这与非癌症队列中的模式不同，后者在很大程度上反映了一般人群随机临床试验中的发现。
