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Discontinuation vs Continuation of RAS Inhibition Before Noncardiac Surgery
TAKE-HOME MESSAGE
- In this multicenter randomized discontinuation trial, perioperative withholding of renin–angiotensin system (RAS) inhibitors ahead of noncardiac surgery did not reduce the rate of myocardial injury. However, the rate of acute hypertension was higher among patients who stopped RAS inhibitor therapy before noncardiac surgery than among those who did not. The rate of hypotension was comparable between the two groups.
- These findings suggest that RAS inhibitor treatment, when indicated for chronic medical conditions, can be safely continued ahead of noncardiac surgery. However, further trials are warranted to confirm these findings.
abstract
This abstract is available on the publisher's site.
Access this abstract nowBACKGROUND AND AIMS
Haemodynamic instability is associated with peri-operative myocardial injury, particularly in patients receiving renin–angiotensin system (RAS) inhibitors (angiotensin-converting-enzyme inhibitors/angiotensin II receptor blockers). Whether stopping RAS inhibitors to minimise hypotension, or continuing RAS inhibitors to avoid hypertension, reduces peri-operative myocardial injury remains unclear.
METHODS
From 31 July 2017 to 1 October 2021, patients aged ≥60 years undergoing elective non-cardiac surgery were randomly assigned to either discontinue or continue RAS inhibitors prescribed for existing medical conditions in six UK centres. Renin–angiotensin system inhibitors were withheld for different durations (2–3 days) before surgery, according to their pharmacokinetic profile. The primary outcome, masked to investigators, clinicians, and patients, was myocardial injury [plasma high-sensitivity troponin-T (hs-TnT) ≥ 15 ng/L within 48 h after surgery, or ≥5 ng/L increase when pre-operative hs-TnT ≥15 ng/L]. Pre-specified adverse haemodynamic events occurring within 48 h of surgery included acute hypertension (>180 mmHg) and hypotension requiring vasoactive therapy.
RESULTS
Two hundred and sixty-two participants were randomized to continue (n = 132) or stop (n = 130) RAS inhibitors. Myocardial injury occurred in 58 (48.3%) patients randomized to discontinue, compared with 50 (41.3%) patients who continued, RAS inhibitors [odds ratio (for continuing): 0.77; 95% confidence interval (CI) 0.45–1.31]. Hypertensive adverse events were more frequent when RAS inhibitors were stopped [16 (12.4%)], compared with 7 (5.3%) who continued RAS inhibitors [odds ratio (for continuing): 0.4; 95% CI 0.16–1.00]. Hypotension rates were similar when RAS inhibitors were stopped [12 (9.3%)] or continued [11 (8.4%)].
CONCLUSIONS
Discontinuing RAS inhibitors before non-cardiac surgery did not reduce myocardial injury, and could increase the risk of clinically significant acute hypertension. These findings require confirmation in future studies.
Additional Info
Discontinuation vs. continuation of renin-angiotensin system inhibition before non-cardiac surgery: the SPACE trial
Eur Heart J 2023 Nov 07;[EPub Ahead of Print], GL Ackland, A Patel, TEF Abbott, S Begum, P Dias, DR Crane, S Somanath, A Middleditch, S Cleland, A Gutierrez Del Arroyo, D Brealey, RM PearseFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Stopping Perioperative Angiotensin II Converting Enzyme inhibitors and/or Receptor Blockers in Major Noncardiac Surgery
Labile blood pressure in the perioperative period is associated with the risks of myocardial injury and higher mortality.1 Renin–angiotensin aldosterone system (RAAS) inhibitors (angiotensin-converting enzyme inhibitors and angiotensin receptor blockers) are often prescribed in patients who are undergoing major noncardiac surgery. There is currently no consensus whether continuing or stopping RAAS inhibitors for noncardiac surgery increases blood pressure lability and/or myocardial injury.2,3
The SPACE phase II randomized controlled trial investigated whether continuing or discontinuing RAAS inhibitors causes myocardial injury after noncardiac surgery.4 Overall, 260 patients over the age of 60 years who underwent major noncardiac surgery were randomized to either continue or stop taking RAAS inhibitors during the perioperative period. The study design accounted for the pharmacokinetic profile of each angiotensin II converting enzyme inhibitor or angiotensin receptor blocker by adjusting when each individual RAAS inhibitor was withdrawn. The authors highlight that other studies have not allowed for different drug-specific “wash out” periods, which may account for inconsistent results in the literature.
The primary outcome of the study was myocardial injury, defined using the VISION study criteria.5 The secondary outcomes were the incidence of major adverse cardiovascular events, infection, and mortality 30 days after randomization. The safety outcomes included hypotension (defined by the use of vasoactive medication), acute hypertension (systolic BP, >180 mm Hg) from randomization until 48 hours after surgery, and acute kidney injury (KDIGO definition).
No difference in the risk of myocardial injury was observed between the groups: 41% in the continuation group versus 48% in the discontinuation group (OR, 0.77; P = .33). There were no differences for the risk of the secondary outcomes, including major adverse cardiovascular events.
Clinically significant use of vasoactive medication was similar between groups, but there were more serious hypertensive events when RAAS inhibitors were withheld: 16 (12.4%) in discontinuation group versus 7 (5.3%) in continuation group.
While common clinical dogma dictates that we should stop RAAS inhibitors perioperatively to limit the risk of hypotension (and, by extension, myocardial injury), the SPACE trial suggests that there is a detrimental impact of stopping RAAS inhibitors by increasing the risk of acute hypertension after surgery. These findings require confirmation in future larger studies.
References