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

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.

Association between Gout, Urate-Lowering Therapy, and Risk of Developing Type 2 Diabetes Mellitus: A Nationwide Population-Based Retrospective Cohort Study

“…The patients presented a wide range of demographic characteristics, which facilitated stratified analyses based on age, sex, and comorbidities, without losing precision, while avoiding bias from selection, nonresponse, or poor recall. The LHID has been shown to have appropriate levels of accuracy and completeness based on prescriptions and clinical diagnosis records [ 30 ]. In addition, we adjusted for numerous potentially confounding factors that are associated with T2DM over long observation periods.…”

Association Between Angiotensin II Receptor Blockers and the Risk of Lung Cancer Among Patients With Hypertension From the Korean National Health Insurance Service-National Health Screening Cohort

“…These findings of the protective effect of ARBs on the risk of lung cancer are consistent with those of several previous studies. Observational studies and a meta-analysis reported an inverse association between ARB use and risk of lung cancer [10][11][12]14]. A cohort study using the Taiwan claims database reported a decreased risk of lung cancer of ARB users compared with ARB non-users (HR, 0.62; 95% CI, 0.53 to 0.73) [11].…”

“…However, the effect of ARBs on lung cancer risk may vary depending on the reference medication. Cohort studies from the Taiwanese claims database also reported protective effects of ARBs on lung cancer [11,12]. However, these studies lacked important covariates including smoking status and were based on a user and nonuser study design, which could introduce a healthy user bias [13].…”

Angiotensin-Converting Enzyme Inhibitors Have Adverse Effects in Anti-Angiogenesis Therapy for Hepatocellular Carcinoma

“…Higher quality research has gradually emerged in recent years. For example, Hicks et al con rmed that the long-term use of ACEIs for more than 5 years clearly promotes lung cancer [18,52]. The effects of ACEIs in tumor-bearing mice also differ across different tumor types, different tumor-bearing mouse models and different drug dosages.…”