(A-096) The association between angiotensin-converting enzyme inhibitors and the risk of diabetic retinopathy in patients with type 2 diabetes: a population-based real world study

Background: RCTs suggest angiotensin-converting enzyme inhibitors (ACEI) may reduce diabetic retinopathy (DR) risk in type 2 diabetes (T2DM), but direct ACEI-angiotensin receptor blockers (ARB) comparisons lack sufficient evidence and real-world evidence remains limited.

Objectives: To investigate the association between ACEI use and the risk of developing DR in T2DM.

Methods: Using the Yinzhou Regional Health Information Platform (YRHIP), a cohort study and a matched nested case-control study both compared DR risk between new ACEI and ARB users among T2DM patients in Ningbo (January 1, 2012 to December 31, 2022). The nested case-control study involved identifying DR cases within the cohort, then matching them to non-DR patients based on age and gender (1:4 matching). An active comparator new-user design was implemented, defining new users as those without ACEI/ARB prescriptions during a 6-month washout baseline period before their first prescription (index date). Follow-up spanned from index date until first DR diagnosis or death or last medical record, or study end. Primary analysis was conducted using an intention-to-treat (ITT) approach. Univariate and multivariate Cox regression models, as well as the primary analytical approach propensity score matching (PSM) at a 1:1 ratio (in cohort study) and 1:2 ratio (in case-control study), were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of DR risk for ACEI vs ARB use. A dose-response relationship was assessed via tertiles of cumulative ACEI vs ARB use duration. Subgroup analyses were by baseline age, gender, fasting plasma glucose, history of hypertension, and duration of T2DM at index date. Sensitivity analyses included inverse probability of treatment weighting to control baseline confounding, competing risk analysis, re-analysis using different latency periods, and restricting to participants with ≥2 baseline prescriptions.

Results: A cohort of 3,677 ACEI and 17,680 ARB users identified 1,077 new DR cases. ACEI use was associated with a lower risk of DR in univariate, multivariate, and PSM analyses ([HR (95% CI): 0.79 (0.66-0.95); 0.81 (0.68-0.98); 0.80 (0.64-0.99)]). Longer ACEI use (>0.94 years) further reduced risk (HR: 0.62 [0.42–0.90]). In the nested case-control study (902 ACEI users, 4,483 ARB users, 1,077 new DR cases), ACEI use again lowered DR risk in univariate, multivariate, and PSM models ([HR (95% CI): 0.78 (0.66-0.94); 0.79 (0.65-0.95); 0.74 (0.61-0.91)]). All subgroup and sensitivity analyses supported these findings, indicating no significant subgroup effect modifiers and no competing risk from all-cause mortality.

Conclusions: ACEI use may lower DR risk compared to ARB use in Chinese T2DM patients, suggesting clinical benefits for DR prevention and management.