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

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.