Jeremy M. H. Hui1,2, Jiandong Zhou3, Yan Hiu A. Lee1,4, Oscar H. I. Chou1,2, Teddy T. L. Lee5, Tong Liu6, Abraham K. C. Wai5, Bernard M. Y. Cheung2, Qingpeng Zhang7, Gary Tse6,8
1Cardiovascular Pharmacology Unit, Cardiovascular Analytics Group, China-UK Collaboration, Hong Kong, China;
2Department of Medicine, The University of Hong Kong, Hong Kong, China;
3Nuffield Department of Medicine, University of Oxford, Oxford, UK;
4Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Hong Kong, China;
5Emergency Medicine Unit, The University of Hong Kong, Hong Kong, China;
6Department of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China;
7School of Data Science, City University of Hong Kong, Hong Kong, China;
8Department of Medicine, Kent and Medway Medical School, Kent, UK
Correspondence to: Gary Tse. Department of Medicine, Kent and Medway Medical School, Kent, UK. Email: gary.tse@kmms.ac.uk.
Background: The effects of angiotensin receptor blockers (ARB) and angiotensin-converting enzyme inhibitors (ACE-I) on new-onset respiratory tract infections remain unclear. This study aimed to compare the risks of pneumonia and lung infections between ARB and ACE-I users.
Methods: This retrospective cohort study included patients who were prescribed ARB/ACE-I in Hong Kong between 1st January 2000 and 31st August 2020. The primary outcomes were new-onset pneumonia and new-onset bacterial, viral, and influenza lung infections. The secondary outcomes were pneumonia, cardiovascular, and all-cause mortality. Patients <18 years old or with prior diagnoses of the above events were excluded. A one-year lag time since initial ARB/ACE-I use was introduced to account for the latency of outcomes and reverse causality. 1:1 propensity score matching was performed based on demographics, prior comorbidities, use of other medications, and laboratory tests.
Results: After 1:1 propensity score matching, the study cohort consisted of 54,436 ARB users (45.9% male, mean age: 69.3±13.6 years, median follow-up time: 4.8 years [interquartile range (IQR): 3.1–7.8)] and 54,436 matched ACE-I users [54.0% male, mean age: 68.3±13.6 years, median follow-up time: 7.6 years (IQR: 4.3–13.5)]. ARB use was associated with higher risks of pneumonia [hazard ratio (HR): 5.73, 95% confidence interval (CI): 4.49–7.32, P<0.0001], bacterial lung infection (HR: 4.17, 95% CI: 2.94–5.91, P<0.0001), viral lung infection (HR: 4.02, 95% CI: 1.83–8.83, P=0.0005), influenza lung infection (HR: 9.84, 95% CI: 6.61–14.63, P<0.0001), pneumonia mortality (HR: 2.86. 95% CI: 2.78–2.95, P<0.0001), cardiovascular mortality (HR: 2.36, 95% CI: 2.30–2.42, P<0.0001), and all-cause mortality (HR: 1.82, 95% CI: 2.30–2.42, P<0.0001) than ACE-I use. These associations remained significant across follow-up times since initial ARB/ACE-I use. However, in the first three years, there were no significant differences in the risks of bacterial and viral lung infections, and mortality between ARB and ACE-I users. The results were confirmed by sensitivity analyses with cause-specific hazard models and sub-distribution hazard models.
Conclusions: The use of ARB was associated with higher risks of pneumonia, lung infections, and mortality than ACE-I use. The decision whether to prescribe ARB or ACE-I for short-term treatment should be made by weighing pneumonia and mortality risks.
Keywords: Angiotensin receptor antagonists; angiotensin-converting enzyme inhibitors; pneumonia; influenza; mortality
