Association between Angiotensin-Converting Enzyme Inhibitors and Lung Cancer-A Nationwide, Population-Based, Propensity Score-Matched Cohort Study

Shih-Yi Lin; Cheng-Li Lin; Cheng-Chieh Lin; Wu-Huei Hsu; Chia-Der Lin; I-Kuan Wang; Chung-Y Hsu; Chia-Hung Kao

doi:10.3390/cancers12030747

Association between Angiotensin-Converting Enzyme Inhibitors and Lung Cancer-A Nationwide, Population-Based, Propensity Score-Matched Cohort Study

Cancers (Basel). 2020 Mar 21;12(3):747. doi: 10.3390/cancers12030747.

Authors

Shih-Yi Lin^{1

2}, Cheng-Li Lin^{3

4}, Cheng-Chieh Lin^{1

5}, Wu-Huei Hsu^{1

6}, Chia-Der Lin^{1

7}, I-Kuan Wang^{1

2}, Chung-Y Hsu¹, Chia-Hung Kao^{1

8

9

10}

Affiliations

¹ Graduate Institute of Biomedical Sciences and School of Medicine, College of Medicine, China Medical University, Taichung 40447, Taiwan.
² Division of Nephrology and Kidney Institute, China Medical University Hospital, Taichung, Taiwan.
³ Management Office for Health Data, China Medical University Hospital, Taichung 40447, Taiwan.
⁴ College of Medicine, China Medical University, Taichung 40447, Taiwan.
⁵ Department of Family Medicine, China Medical University Hospital, Taichung 40447, Taiwan.
⁶ Department of Chest Medicine, China Medical University Hospital, Taichung 40447, Taiwan.
⁷ Department of Otolaryngology, China Medical University Hospital, Taichung 40447, Taiwan.
⁸ Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung 40447, Taiwan.
⁹ Department of Bioinformatics and Medical Engineering, Asia University, Taichung 40447, Taiwan.
¹⁰ Center of Augmented Intelligence in Healthcare, China Medical University Hospital, Taichung 40447, Taiwan.

Abstract

Background: Direct evidence of lung cancer risk in Asian users of angiotensin-converting enzyme inhibitors (ACEIs) is lacking.

Methods: The ACEI cohort comprised 22,384 patients aged ≥ 18 years with a first prescription of ACEI. The comparison angiotensin receptor blocker (ARB) cohort consisted of age-, sex- and comorbidity-matched patients at a ratio of 1:1. The primary outcome was the incidence of lung cancer, which was evaluated using a proportional hazard model.

Results: The overall incidence rates of lung cancer in the ACEI and ARB cohorts were 16.6 and 12.2 per 10,000 person-years, respectively. The ACEI cohort had a significantly higher risk of lung cancer than the ARB cohort (adjusted hazard ratio [aHR]. = 1.36; 95% confidence interval [CI]. = 1.11-1.67). Duration-response and dose-response analyses revealed that compared with patients who did not receive ACEIs, patients who received ACEIs for more than 45 days per year (aHR = 1.87; 95% CI = 1.48-2.36) and patients who received more than 540 defined daily doses of ACEIs per year (aHR =1.80; 95% CI = 1.43--2.27) had a significantly higher risk of lung cancer. The cumulative incidence of lung cancer was also significantly higher in the ACEI cohort than in the ARB cohort (log-rank test, p = 0.002).

Conclusions: ACEI use is associated with an increased risk of lung cancer compared with ARB use. Patients using ARBs have a significantly lower risk of lung cancer than non-ARB users.

Keywords: air pollutant; angiotensin-converting enzyme inhibitors (ACEIs); lung cancer.