Key result
Long-term ACEIs/ARBs linked to ~26% lower risk of moderate-to-severe acute postoperative pain in hypertensive patients.
Why the study?
ACEIs and ARBs may influence pain perception through neuroinflammatory and hormonal pathways, but their impact on acute postoperative pain has not been well characterized.
Does long-term ACEI/ARB use reduce acute postoperative pain in hypertensive patients undergoing non-cardiac surgery?
Cohort (n=1,206)
No
Does long-term ACEI/ARB use reduce acute postoperative pain in hypertensive patients undergoing non-cardiac surgery?
Effect estimate: OR 0.74 (95% CI 0.57-0.94)
Absolute Event Rate: 60.4% vs 67.3%
p-value: p=0.015
Long-term ACEI/ARB use in hypertensive patients is associated with a significant reduction in moderate-to-severe acute postoperative pain on the first day after non-cardiac surgery.
May support perioperative ACEI/ARB continuation in hypertensives; extends low-certainty evidence but leaves open causality pending RCTs.
Background: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are commonly used for hypertension management. Emerging evidence suggests that these agents may influence pain perception through neuroinflammatory and hormonal pathways. However, their impact on acute postoperative pain has not been well characterized. Aim: This study aimed to explore the hypothesis that long-term ACEI/ARB use is associated with reduced acute postoperative pain in hypertensive patients undergoing non-cardiac surgery. Methods: We conducted a hybrid study combining a retrospective cohort analysis with a drug-target Mendelian randomization approach. A total of 1206 hypertensive patients who underwent general anesthesia and received patient-controlled intravenous analgesia were included. The primary outcome was the presence of moderate-to-severe postoperative pain, which was defined as a numerical rating scale (NRS) score ≥ 4 on postoperative days (PODs) 1 and 3. Secondary outcomes included opioid consumption measured in morphine milligram equivalents. Confounders were adjusted using inverse probability of treatment weighting. Missing data was treated by multiple imputation with chained equation, as 37.3% of POD3 NRS missing. Genetic validation was performed using expression quantitative trait loci for ACEI/ARB target genes and genome-wide association data on multisite chronic pain. Results: Patients receiving ACEIs/ARBs had significantly lower rates of moderate-to-severe pain on postoperative day 1 (OR 0.74, 95% CI 0.57– 0.94; ARR 6.87%; NNT 14.6) but had no significance on day 3 (OR 0.77, 95% CI 0.57– 1.04), despite similar opioid consumption on both days. Genetic validation found associations between several ACEI/ARB target genes and reduced chronic pain risk, directionally consistent with our clinical observations. Conclusion: Long-term ACEI/ARB use may offer potential analgesic benefits for surgical patients with hypertension. These preliminary findings provide a foundation for future research to explore their potential role in perioperative pain management.
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Li et al. (2026) conducted a cohort in Hypertension undergoing non-cardiac surgery (n=1,206). ACEIs or ARBs vs. No ACEI/ARB use was evaluated on Moderate-to-severe acute postoperative pain (NRS ≥4) on postoperative day 1 (OR 0.74, 95% CI 0.57-0.94, p=0.015). Long-term use of ACEIs or ARBs was associated with a significantly lower rate of moderate-to-severe acute postoperative pain on postoperative day 1 (OR 0.74) in hypertensive surgical patients.
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