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A Systematic Review of Outcomes Associated With Withholding or Continuing Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Before Noncardiac Surgery

Hollmann, Caryl, MBChB, DA(SA); Fernandes, Nicole L., MBChB, DA(SA); Biccard, Bruce M., MBChB, FCA, PhD

doi: 10.1213/ANE.0000000000002837
Patient Safety: Meta-Analysis

BACKGROUND: The global rate of major noncardiac surgical procedures is increasing annually, and of those patients presenting for surgery, increasing numbers are taking either an angiotensin-converting enzyme inhibitor (ACE-I) or an angiotensin receptor blocker (ARB). The current recommendations of whether to continue or withhold ACE-I and ARB in the perioperative period are conflicting. Previous meta-analyses have linked preoperative ACE-I/ARB therapy to the increased incidence of postinduction hypotension; however, they have failed to correlate this with adverse patient outcomes. The aim of this meta-analysis was to determine whether continuation or withholding ACE-I or ARB therapy in the perioperative period is associated with mortality and major morbidity.

METHODS: This meta-analysis was prospectively registered on PROSPERO (CRD42017055291). A comprehensive search of MEDLINE (PubMed), CINAHL (EBSCO host), ProQuest, Cochrane database, Scopus, and Web of Science was conducted on December 6, 2016. We included adult patients >18 years of age on chronic ACE-I or ARB therapy who underwent noncardiac surgery in which ACE-I or ARB was either withheld or continued on the morning of surgery. Primary outcomes included all-cause mortality and major cardiac events (MACE). Secondary outcomes included the risk of congestive heart failure, acute kidney injury, stroke, intraoperative/postoperative hypotension, and the length of hospital stay.

RESULTS: After abstract review, the full text of 25 studies was retrieved, of which 9 fulfilled the inclusion criteria: 5 were randomized control trials, and 4 were cohort studies. These studies included a total of 6022 patients on chronic ACE-I/ARB therapy before noncardiac surgery. A total of 1816 patients withheld treatment the morning of surgery and 4206 continued their ACE-I/ARB. Preoperative demographics were similar between the 2 groups. Withholding ACE-I/ARB therapy was not associated with a difference in mortality (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.62–1.52; I 2 = 0%) or MACE (OR, 1.12; 95% CI, 0.82–1.52; I 2 = 0%). However, withholding therapy was associated with significantly less intraoperative hypotension (OR, 0.63; 95% CI, 0.47–0.85; I 2 = 71%). No effect estimate could be pooled concerning length of hospital stay and congestive heart failure.

CONCLUSIONS: This meta-analysis did not demonstrate an association between perioperative administration of ACE-I/ARB and mortality or MACE. It did, however, confirm the current observation that perioperative continuation of ACE-I/ARBs is associated with an increased incidence of intraoperative hypotension. A large randomized control trial is necessary to determine the appropriate perioperative management of ACE-I and ARBs.

From the Department of Anaesthesia and Perioperative Medicine, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa.

Published ahead of print January 29, 2018.

Accepted for publication December 19, 2017.

Funding: No outside funding was utilized in the search and retrieval of all articles. All funding was from departmental resources.

Conflicts of Interest: See Disclosures at the end of the article.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website.

PROSPERO registry: CRD42017055291.

Reprints will not be available from the authors.

Address correspondence to Caryl Hollmann, MBChB, DA(SA), Department of Anaesthesia and Perioperative Medicine, D23, Groote Schuur Hospital, University of Cape Town, Observatory, Cape Town 7925, South Africa. Address e-mail to

© 2018 International Anesthesia Research Society
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