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Abstract Background There is a growing concern that the use of anti-hypertensives may be associated with an increased risk of cancer, but it remains uncertain for the association between anti-hypertensives and lung cancer risk, as well as their interaction with aspirin in chemoprotective effects. Methods The goal of this study is to assess the association between anti-hypertensives use and the risk of lung cancer, as well as the chemopreventive impacts from the combination usage of aspirin and anti-hypertensives. A retrospective cohort study was conducted based on all the public hospital electronic medical records in Hong Kong. Patients with prescription records of anti-hypertensives (ACEi/ARB, CCB, β-blocker,α-blocker) and/or aspirin were included as the exposure groups. Using the Cox proportional hazards model with inverse probability weighting, we estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for lung cancer risk from anti-hypertensives usage or combination usage of aspirin with anti-hypertensives. The likelihood ratio test and interaction model were adopted for exploring the interaction effects with aspirin. Results A total of 6592 and 84,116 lung cancer cases were identified from the groups of anti-hypertensives users and anti-hypertensives users with aspirin, respectively. The group of non-aspirin patients who received anti-hypertensives showed a significantly lower risk of lung cancer (HR: 0.63, 95% CI: 0.60–0.66), compared to those without anti-hypertensives. When aspirin and α-blocker were used simultaneously, it could lower the risk of lung cancer significantly (HR: 0.53, 95% CI: 0.34–0.84). Moreover, the lower risk of lung cancer persisted with a longer follow-up period of anti-hypertensives usage. Combination usage with aspirin in the users of ACEi/ARB, CCB, and α-blocker showed significant interaction effects. However, the smoking effect could not be eliminated in this analysis. Discussion Anti-hypertensive treatment was associated with a lower risk of lung cancer, which is associated with the anti-hypertensives exposure period. The potential interaction on the chemopreventive influence from combination usage of α-blocker and aspirin might exist. More corroborations on these findings are needed to focus on the different settings in future studies. |