BACKGROUND: Use of angiotensin converting enzyme inhibitors (ACEI) 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. METHODS AND RESULTS: We conducted a nested case-control study using data from four Danish national health and administrative registries. New users of ACEIs or ARBs in Denmark from 1 Jan 2000 were followed until 31 December 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 (OR) for incident, histologically verified lung cancer with high use of ACEIs defined as a cumulative dose above 3650 defined daily doses (DDD). We examined different cumulative doses of ACEI (≤1800, 1801-3650, >3650 DDDs), 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% confidence interval (CI) 1.08 to 1.62). Lower cumulative doses showed neutral associations (≤1800 DDDs OR 1.01 95% CI 0.94 to 1.09; 1801-3650 DDDs OR 1.03, 95% CI 0.90 to 1.19). Confidence intervals 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). CONCLUSIONS: Use of high cumulative ACEI doses was associated with modestly increased odds of lung cancer while use of lower doses showed neutral associations. The established benefits of ACEIs should be considered when interpreting these findings.
|Journal||Circulation: Cardiovascular Quality and Outcomes.|
|Publication status||Accepted - 23 Oct 2020|