Abstract
BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are both recommended as first-line antihypertensive agents for patients with diabetes. While pharmacological mechanisms suggest that ACEIs may provide better cardiovascular protection than ARBs, this potential benefit has not been fully established in previous observational studies of patients with diabetes. METHODS: An active-comparator new-user design within target trial emulation framework was implemented using Yinzhou Regional Health Care Database (YRHCD). We compared risks of major cardiovascular events (MACE) between older patients (age ≥ 65 years) with type 2 diabetes mellitus (T2DM) newly exposed to ACEIs and ARBs from January 1, 2010 to May 31, 2023. The primary outcomes were 3-point MACE, including hospitalized myocardial infarction, hospitalized stroke, and all-cause mortality (a proxy for cardiovascular mortality). We also assessed 4-point MACE, which further included hospitalized heart failure. Propensity scores were calculated to balance 44 identified confounders. Marginal structure models were applied to estimate per-protocol hazard ratios. RESULTS: A total of 18,558 individuals were included, with 1,641 initiating ACEIs and 16,917 initiating ARBs. Their median age was 72 years and 45% were male. The adjusted hazard ratio for ACEIs vs. ARBs was 0.86 (95% confidence interval [CI], 0.68-1.10) for 3-point MACE and 0.83 (95% CI 0.69-0.99) for 4-point MACE. The 1-year absolute risk differences were - 0.30% (95% CI - 1.80-1.21%) for 3-point MACE and - 1.16% (95% CI - 2.97-0.66%) for 4-point MACE. Results were consistent across subgroup analyses (stratified by age, sex, as well as baseline major atherosclerotic cardiovascular disease, heart failure, other antihypertensive therapy, insulin therapy, and calendar year) and sensitivity analyses. CONCLUSIONS: Among older patients with T2DM, the initiation of ACEIs was associated with a trend toward lower risk of MACE compared to ARBs, implying the potential cardiovascular benefits of ACEIs in this population.