Perioperative Continuation Versus Withholding of Angiotensin Receptor Blockers and Postoperative Delirium in Elderly Patients: A Randomized Exploratory Trial

Objective Postoperative delirium (POD) is a frequent complication after surgery in older adults and is associated with increased morbidity and prolonged recovery. The impact of perioperative management of angiotensin receptor blockers (ARBs) on POD remains uncertain. This randomized exploratory trial investigated the association between perioperative ARB continuation or withholding and POD outcomes in elderly patients undergoing elective surgery. Methods Elderly patients (≥65 years) receiving chronic ARB therapy and undergoing elective surgery were randomly assigned to either perioperative ARB continuation or temporary ARB withholding. The allocated ARB management strategy was applied during the perioperative period, and POD was assessed daily for 5 postoperative days using the Confusion Assessment Method (CAM). Delirium severity was evaluated using the Delirium Rating Scale-Revised-98 (DRS-R-98). Plasma levels of neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), interleukin-6 (IL-6), interleukin-8 (IL-8), and C-reactive protein (CRP) were evaluated as exploratory biomarkers. Results Among 44 randomized participants, 42 were included in the final analysis (21 per group). POD occurred in 4/21 participants (19.1%) in the ARB continuation group and 12/21 participants (57.1%) in the ARB withholding group, corresponding to an absolute risk difference of −38.1 percentage points (95% confidence interval, −59.7 to −8.7; P = 0.025). Surgical category was markedly imbalanced between groups, with orthopedic procedures accounting for 57.1% of the ARB continuation group and 95.2% of the ARB withholding group ( P = 0.009). Lower DRS-R-98 scores were observed in the ARB continuation group compared with the ARB withholding group: median (interquartile range, IQR), 0 (0-7) vs 18 (5-26), P = 0.025, accompanied by shorter delirium duration (median (IQR), 0 (0-40) vs 40 (12-100) hours, P = 0.030). Exploratory biomarker analyses showed smaller postoperative relative increases in NfL, GFAP, and IL-8 in the ARB continuation group, whereas IL-6 and CRP did not differ significantly between groups after false discovery rate (FDR) correction. These biomarker findings are exploratory and should not be interpreted as evidence of causal or mechanistic effects. Conclusions In this small randomized exploratory trial, perioperative ARB continuation was associated with lower observed POD incidence and severity compared with temporary ARB withholding. However, the marked imbalance in surgical category and the limited sample size preclude independent attribution of these differences to ARB management. These findings are hypothesis-generating and require confirmation in larger, adequately powered randomized studies with better balance of surgical procedures.