From the Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Division of Cardiology, Department of Medicine, University of North Carolina at Chapel Hill, NC.
Epidemiology. 2019 Nov;30(6):867-875. doi: 10.1097/EDE.0000000000001065.
Biologic evidence suggests that angiotensin II may play a role in tumor progression or growth. We compared the short-term colorectal cancer (CRC) risk among initiators of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) versus guideline-recommended clinical alternatives (beta blockers, calcium channel blockers [CCB], and thiazides).
We conducted a new-user cohort study on U.S. Medicare beneficiaries aged over 65 years, who initiated antihypertensive monotherapy during 2007-2013 and were free of cancer diagnosis before drug initiation. Follow-up began 6 months postinitiation to allow time for the diagnostic delay. We estimated hazard ratios (HR) with 95% confidence intervals (CI) using propensity score weighted Cox regression, overall and stratified by time since drug initiation, and 5-year cumulative risk differences (RD) using Kaplan-Meier estimator. We assessed the potential for unmeasured confounding using supplemental data from Medicare Current Beneficiary Survey.
For analyses without censoring for treatment changes, we observed 532 CRC events among 111,533 ACEI/ARB initiators. After a median follow-up of 2.2 years (interquartile range: 1.0-3.7), CRC risk was similar between ACEI/ARB and active comparators, with adjusted HRs of 1.0 (95% CI = 0.85, 1.1) for ACEI/ARB versus beta blockers, 1.2 (95% CI = 0.97, 1.4) for ACEI/ARB versus CCB and 1.0 (95% CI = 0.80, 1.3) for ACEI/ARB versus thiazide. Five-year RDs and as-treated analyses, which censored follow-up at medication changes, produced similar findings.
Based on real-world antihypertensive utilization patterns in Medicare beneficiaries, our study suggests no association between ACEI/ARB initiation and the short-term CRC risk.
生物学证据表明，血管紧张素 II 可能在肿瘤的进展或生长中发挥作用。我们比较了血管紧张素转换酶抑制剂（ACEI）或血管紧张素受体阻滞剂（ARB）与指南推荐的临床替代药物（β受体阻滞剂、钙通道阻滞剂[CCB]和噻嗪类利尿剂）使用者短期结直肠癌（CRC）风险。
我们对美国 Medicare 受益人群中年龄超过 65 岁的患者进行了一项新使用者队列研究，这些患者在 2007 年至 2013 年期间开始接受单一抗高血压药物治疗，且在药物治疗开始前没有癌症诊断。随访从药物治疗开始后 6 个月开始，以留出诊断延迟的时间。我们使用倾向评分加权 Cox 回归估计风险比（HR）和 95%置信区间（CI），总体和按药物治疗开始后时间分层，并使用 Kaplan-Meier 估计器估计 5 年累积风险差异（RD）。我们使用 Medicare 现收现付受益人调查的补充数据评估潜在的未测量混杂因素。
在不考虑治疗变化的情况下进行分析时，我们在 111533 名 ACEI/ARB 使用者中观察到 532 例 CRC 事件。中位随访时间为 2.2 年（四分位距：1.0-3.7），ACEI/ARB 与活性对照药物之间的 CRC 风险相似，ACEI/ARB 与β受体阻滞剂相比，调整后的 HR 为 1.0（95%CI=0.85，1.1），ACEI/ARB 与 CCB 相比，HR 为 1.2（95%CI=0.97，1.4），ACEI/ARB 与噻嗪类利尿剂相比，HR 为 1.0（95%CI=0.80，1.3）。对药物变化时进行随访 censoring 的 5 年 RD 和按治疗分析得出了相似的结果。
根据 Medicare 受益人群中真实的抗高血压药物使用情况，我们的研究表明 ACEI/ARB 起始与短期 CRC 风险之间没有关联。
