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BackgroundDiabetes is associated with increased risk of respiratory infections. Renin-angiotensin system (RAS) inhibition with anti-fibrotic, anti-inflammatory effects may reduce pneumonia risk. Prior studies did not account for time-varying and cumulative exposure to RAS inhibitors (RASi), with short follow-up periods, nor compared angiotensin converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) use in Asians. We investigated the association of long-term use of RASi with risk of pneumonia and related death in Chinese people with diabetes using electronic medical record (EMR) data.MethodsThis was a prospective analysis of EMR with overlap propensity-score weighting of a territory-wide cohort (n=252,616, 1.7 million person-years) and a register-based cohort (n=13,017, 0.1 million person-years) in Hong Kong. We compared new-users of RASi (ACEi/ARBs) following baseline assessment with non-RASi users and new-users of calcium-channel blockers as active comparator. The main outcome was first hospitalization and death from pneumonia. ResultsAmongst 252,616 patients with diabetes in the population-based cohort (mean age=61.0 [SD=12.2] years), 73,161 were new-ACEi-only users; 20,907 new-ARBs-only users; 38,778 ACEi/ARBs users; and 119,770 never-ACEi/ARBs users. Over a mean follow-up period of 6.7 years, 5.2% (n=13,057) of patients had pneumonia and 2.2% (n=5,480) died with pneumonia. Compared with non-RASi use, time-varying RASi exposure was associated with reduced risk of pneumonia (hazard ratio, HR, 95% CI): 0.78 (0.75-0.82) and pneumonia-related death (HR=0.49, 0.46-0.53). The respective HRs for ARBs-only were 0.70 (0.62-0.78) and 0.41 (0.33-0.52) and that of ACEi-only were 0.98 (0.91-1.05) and 0.77 (0.68-86). In the Aalen-additive hazards model, the effect of RASi use was time-invariant for pneumonia (P=0.340) and time-varying for related death (P |
