Time-varying risk associations of renin angiotensin system inhibitors with pneumonia and related deaths in a cohort of 252,616 patients with diabetes (2002-2019)

Aims: To evaluate the time-varying and cumulative risk associations of renin-angiotensin-system-inhibitors (RASi) with pneumonia and related deaths in people with diabetes. Methods: This was a prospective analysis with propensity-score overlap-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) of patients with diabetes in Hong Kong. We compared risk of pneumonia and related death in new-users of angiotensin-converting-enzyme-inhibitor (ACEi) and angiotensin-receptor-blocker (ARBs) with non-RASi users and newusers of calcium-channel-blockers as active comparator. Results: Amongst 252,616 people with diabetes (99.3% type 2 diabetes) in the population-based cohort with a mean follow-up of 6.7 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. Time-varying RASi exposure was associated with reduced risk of pneumonia (HR = 0.78, 95% CI: 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). The attenuated risk association of RASi use was time-invariant for pneumonia (P = 0.340) and time-varying for related-death (P < 0.001) with prevention of 0.6 (0.2-0.9) and 1.4 (1.0-1.6) per-1000-person-years events and deaths, respectively. Conclusions: Long-term use of RASi, notably ARBs, was associated with reduced risk of pneumonia and related deaths in Chinese people with diabetes.

Automated summary

This study evaluated the risk associations between renin-angiotensin-system inhibitors (RASi) and pneumonia as well as related deaths in individuals with diabetes. The results showed that long-term use of RASi, particularly ARBs, was associated with a reduced risk of pneumonia and related deaths in Chinese people with diabetes.