Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Denmark (K.B.K., A.P.).
Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, United Kingdom (B.H.).
Circ Cardiovasc Qual Outcomes. 2021 Jan;14(1):e006687. doi: 10.1161/CIRCOUTCOMES.120.006687. Epub 2021 Jan 13.
Use of angiotensin-converting enzyme inhibitors (ACEIs)was associated with increased risk of lung cancer in a cohort study from the United Kingdom. We aimed to replicate these findings in a Danish population.
We conducted a nested case-control study using data from 4 Danish national health and administrative registries. New users of ACEIs or angiotensin II receptor blockers in Denmark from January 1, 2000 were followed until December 31, 2015, incident lung cancer, death, or emigration. Each lung cancer case was matched with up to 20 controls on age, sex, duration of follow-up, and year of cohort entry using risk-set sampling. Conditional logistic regression was used to estimate odds ratios (ORs) for incident, histologically verified lung cancer with high use of ACEIs defined as a cumulative dose above 3650 defined daily doses. We examined different cumulative doses of ACEI (≤1800, 1801-3650, >3650 defined daily doses), examined whether the association varied with lung cancer histology, and repeated the analyses using thiazides as active comparator.
We included 9652 lung cancer cases matched to 190 055 controls. High use of ACEIs was associated with lung cancer (adjusted OR, 1.33 [95% CI, 1.08-1.62]). Lower cumulative doses showed neutral associations (≤1800 defined daily doses OR, 1.01 [95% CI, 0.94-1.09]; 1801-3650 defined daily doses OR, 1.03 [95% CI, 0.90-1.19]). CIs were wide and included the null when stratifying on histology. Using thiazides as active comparator yielded comparable results (OR, 1.34 [95% CI, 0.96-1.88]).
Use of high cumulative ACEI doses was associated with modestly increased odds of lung cancer although use of lower doses showed neutral associations. The established benefits of ACEIs should be considered when interpreting these findings.
在一项来自英国的队列研究中，血管紧张素转换酶抑制剂（ACEI）的使用与肺癌风险增加相关。我们旨在丹麦人群中复制这些发现。
我们使用来自丹麦 4 个国家卫生和行政登记处的数据进行了一项嵌套病例对照研究。2000 年 1 月 1 日起，丹麦新使用 ACEI 或血管紧张素 II 受体阻滞剂的患者随访至 2015 年 12 月 31 日，记录肺癌发病、死亡或移民情况。每个肺癌病例均通过风险集抽样，按年龄、性别、随访时间和队列进入年份与至多 20 名对照进行匹配。采用条件逻辑回归估计 ACEI 高用量（累积剂量超过 3650 个定义日剂量）与肺癌发病、组织学确诊病例的比值比（OR）。我们还检验了 ACEI 的不同累积剂量（≤1800、1801-3650、>3650 个定义日剂量），检验了该关联是否随肺癌组织学而异，并使用噻嗪类药物作为活性对照重复了分析。
我们纳入了 9652 例肺癌病例，与 190055 例对照进行了匹配。ACEI 高用量与肺癌相关（校正 OR，1.33[95%CI，1.08-1.62]）。较低的累积剂量显示出中性关联（≤1800 个定义日剂量 OR，1.01[95%CI，0.94-1.09]；1801-3650 个定义日剂量 OR，1.03[95%CI，0.90-1.19]）。当按组织学分层时，CI 较宽且包含零值。使用噻嗪类药物作为活性对照得到了类似的结果（OR，1.34[95%CI，0.96-1.88]）。
尽管使用较低剂量与中性关联，但高累积 ACEI 剂量的使用与肺癌发病几率略有增加相关。在解释这些发现时，应考虑 ACEI 的既定益处。
