Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors Versus Angiotensin Receptor Blockers: Multidatabase Target Trial Emulation Studies

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BACKGROUND: ACE (angiotensin-converting enzyme) inhibitors and ARBs (angiotensin receptor blockers) are equally recommended as first-line treatment for cardiovascular and renal protection in clinical practice. Evidence on the comparative effectiveness of both drugs on long-term death is inconclusive. METHODS: This multidatabase cohort study used a target trial emulation framework based on the UK Biobank database and the China Renal Data System. Participants who were newly prescribed ACE inhibitors or ARBs were included. Primary and secondary outcomes were 5-year all-cause mortality and major adverse cardiovascular events, respectively. Propensity score matching was performed to balance the baseline characteristics. RESULTS: A total of 72 534 and 255 806 patients were identified from the UK Biobank database and the China Renal Data System database. After propensity score matching, cumulative incidence of 5-year all-cause mortality among patients with ACE inhibitor and ARB initiation was 3.45% (3.17%-3.74%) and 3.04% (2.76%-3.31%), with estimated risk differences and hazard ratios of 0.42% (95% CI, 0.02%-0.81%) and 1.13 (95% CI, 1.07-1.19) in the UK Biobank database. Consistent results were obtained in the China Renal Data System database (risk difference, 1.48% [95% CI, 1.10%-1.86%] and hazard ratio, 1.12 [95% CI, 1.09-1.14]). In addition, patients with ACE inhibitor initiation were associated with higher risk of major adverse cardiovascular events than those with ARB initiation in both the China Renal Data System database and UK Biobank database. CONCLUSIONS: This study suggests ACE inhibitor initiation was associated with higher risks of all-cause mortality and major adverse cardiovascular events compared with ARB initiation. These findings highlight the importance of carefully weighing the selection of angiotensin-aldosterone system inhibitors.

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