Impact of Different Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blocker Resumption Timing on...

Evidence suggests a survival benefit from resuming angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) post acute kidney injury (AKI) compared to nonuse; however, the optimal timing and its impact on outcomes are unclear. The risks of earlier resumption, such as recurrent AKI or hyperkalemia, remain unexplored.

Using multiinstitutional electronic health records, we analyzed the relationship between 3 ACEI or ARB (ACEI/ARB) resumption timelines post-AKI (prior to discharge, 0-3 months, and 4-6 months postdischarge) and outcomes including all-cause mortality, major adverse cardiac and cerebrovascular events (MACCEs), dialysis initiation or end-stage renal disease (ESRD), severe hyperkalemia, and recurrent AKI with hospitalization. Cox proportional models estimated hazard ratios (HRs) for outcomes across different resumption timings, following a target trial design.

Among 5392 AKI survivors resuming ACEI/ARB within 6 months post-AKI, earlier resumption was associated with lower mortality, MACCE, MACCE-related mortality, new dialysis initiation or ESRD (P < 0.001 in trend tests), without increased risks of severe hyperkalemia and re-AKI admissions. Early resumption has a lower mortality compared to 4 to 6 months postdischarge (before discharge, HR: 0.88, 95% confidence interval [CI]: 0.83-0.93; 0-3 months, HR: 0.89, 95% CI: 0.85-0.94). Subgroup analysis showed a lower mortality HR from earlier resumption among AKI survivors with prior ACEI/ARB comorbidity indications (P < 0.001 in trend tests; before discharge, HR: 0.85, 95% CI: 0.80-0.90; 0-3 months, HR: 0.88, 95% CI: 0.83-0.93).

Our cohort demonstrates lower risks for mortality, cardiovascular events, and ESRD with early ACEI/ARB resumption, without heightened risks of severe hyperkalemia or rehospitalization for AKI. Early resumption should be considered for patients with indications for ACEI/ARB.