Clinical Inquiries

Does withholding an ACE inhibitor or ARB before surgery improve outcomes?

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EVIDENCE-BASED ANSWER:

A guarded yes, because the evidence of benefit is from observational studies and applies to noncardiac surgery. Withholding angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) 24 hours before noncardiac surgery has been associated with a 30-day lower risk for all-cause death, stroke, myocardial injury, and intraoperative hypotension (18% adjusted relative risk reduction).

The finding is based on 1 international prospective cohort study and, of note, is an association and a likelihood of benefit. Confirmation would require a large randomized trial (RCT; strength of recommendation [SOR]: B, good-quality international prospective cohort study).


 

References

EVIDENCE SUMMARY

An international prospective cohort study analyzed data from 14,687 patients, 4802 of whom were on an ACEI or ARB, to study the effect on 30-day morbidity and mortality of withholding the medications 24 hours before a noncardiac surgery.1 Of the ACEI or ARB users, 26% (1245) withheld their medication and 3557 continued it 24 hours before surgery.

Large study shows benefit in withholding meds

Patients who withheld the ACEI or ARB were less likely to experience the primary composite outcome of all-cause death, stroke, or myocardial injury (150/1245 [12%] vs 459/3557 [12.9%]; adjusted relative risk [RR] = 0.82; 95% confidence interval [CI], 0.70-0.96; P = .01; number needed to treat [NNT] = 116) and intraoperative hypotension (adjusted RR = 0.80; 95% CI, 0.72-0.93; P < .001; NNT = 18). For the NNT calculation, which the investigators didn’t perform, the treatment is the number needed to withhold an ACEI or ARB to show benefit.

Smaller, weaker studies yield different results

A retrospective cohort analysis of propensity-matched ACEI users with ACEI nonusers (9028 in each group) undergoing noncardiac surgery compared intra- and postoperative respiratory complications or mortality.2 The study found no association with either 30-day mortality (odds ratio [OR] = 0.93; 95% CI, 0.73-1.19) or the composite of in-hospital morbidity and mortality (OR = 1.06; 95% CI, 0.97-1.15). Limitations included comparison of users with nonusers as opposed to an intention-to-withhold study, the retrospective nature of the study, and the fact that outcomes were gathered from ICD-9 billing codes rather than obtained prospectively.

A Cochrane review assessed the benefits and harms of perioperative ACEIs or ARBs on mortality and morbidity in adults undergoing any type of surgery.3 Seven RCTs with a total of 571 participants were included in the review. Overall, the review didn’t find evidence to support prevention of mortality, morbidity, and complications by perioperative ACEIs or ARBs because the included studies were of low and very low methodological quality, had a high risk for bias, and lacked power. Moreover, the review didn’t assess the effect of withholding ACEIs or ARBs before surgery.

A random-effects meta-analysis of 5 studies (3 randomized trials and 2 observational studies) totaling 434 patients suggested that patients receiving ACEIs or ARBs immediately before surgery were more likely to develop hypotension requiring vasopressors (RR = 1.50; 95% CI, 1.15-1.96).4 Sufficient data weren’t available to assess other outcomes, and the included studies were relatively small and generally not powered to observe clinically significant consequences nor designed to measure the incidence of patient-important outcomes.

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Evidence-based answers from the Family Physicians Inquiries Network

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