Effects of an Angiotensin Converting Enzyme Inhibitors Versus Angiotensin II Receptor Blockers for Pneumonia, Influenza and Lung Related Mortality Risks: A Retrospective Population-based Cohort Study

Background: The association between increased rates of pneumonia and influenza and long-term exposures of angiotensin-converting enzyme inhibitors (ACEIs) versus angiotensin receptor blockers (ARBs) remained unclear.
Methods: This is a retrospective population-based cohort study using territory-wide healthcare data in Hong Kong. The study period was from 1st January 2000 to 31st August 2020. Patients who used ARB or ACEI were included. ARB and ACEI users were matched using a propensity score at 1:1 ratio with nearest neighbor search strategy. The follow-up started after one-year lag time after drug initiation until outcome, death or end of study. Risks of new onset adverse pneumonia outcomes of bacterial, viral and influenza infections between ARB and ACEI users were estimated using Cox proportional hazards models with competing risks consideration. Subgroup analysis was conducted by stratifying patients with different follow-up time since drug initiation.
Results: In total, 379,201 patients (54,436 ARB users and 324,765 ACEI users) were initially identified. In the propensity score-matched cohort (n ¼ 108,872), ARB use was associated with significantly higher risks in new onset pneumonia and influenza (HR: 5.73, 95 % CI: [4.49e7.32], P value < 0.001), bacterial lung infection (HR: 4.17, 95 % CI: [2.94e5.91], P value < 0.0001), viral lung infection (HR: 4.02, 95 % CI: [1.83e8.83], P value ¼ 0.0005), in particular influenza infection (HR: 9.84, 95 % CI: [6.61e14.63], P value < 0.0001) in 1:1 propensity score-matched control cohorts. In the subgroup analysis stratified by duration of use, the risks of ARB prescription were consistently more severe than ACEI for both primary and secondary outcomes after longer exposure.
Conclusions: Longer exposures of ARB drugs, compared with prescription of ACEI drugs, demonstrated significantly higher risks for adverse pneumonia and influenza risk, and pneumonia and cardiovascular related mortality.

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