Discontinuation vs. continuation of renin-angiotensin system inhibition before non-cardiac surgery: the SPACE trial

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 continui...

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Published in:European heart journal 2024-04, Vol.45 (13), p.1146-1155
Main Authors: Ackland, Gareth L, Patel, Akshaykumar, Abbott, Tom E F, Begum, Salma, Dias, Priyanthi, Crane, David R, Somanath, Sameer, Middleditch, Alexander, Cleland, Stuart, Gutierrez Del Arroyo, Ana, Brealey, David, Pearse, Rupert M
Format: Article
Language:English
Subjects:
Angiotensin Receptor Antagonists - adverse effects
Angiotensin-Converting Enzyme Inhibitors - adverse effects
Antihypertensive Agents - therapeutic use
Clinical Research
Humans
Hypertension - chemically induced
Hypertension - drug therapy
Hypotension - chemically induced
Hypotension - drug therapy
Hypotension - prevention & control
Renin-Angiotensin System
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Summary: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. 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. 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%)]. 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.
ISSN:0195-668X
1522-9645
DOI:10.1093/eurheartj/ehad716