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

Abstract
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 (
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.
Contributors

Tasnin Shahid
Author

Mevan Gooneratne
Author

Charlotte Trainer
Author

Bethan Griffiths
Author

Steven Dunkley
Author

Shaun May
Author

Gareth L Ackland
Author
William Harvey Research Institute London , United Kingdom of Great Britain & Northern Ireland

Sophie Walker
Author

Alexander Fowler
Author

Timothy Stephens
Author

Monica Oliveira
Author

Marta Januszewska
Author

Akshaykumar Patel
Author

Edyta Niebrzegowska
Author

Vanessa Amaral
Author

Jamila Kassam
Author

Sophie Young
Author

Tom E F Abbott
Author

Shanaz Ahmad
Author

Jan Whalley
Author

Salma Begum
Author

Ryan Haines
Author

Priyanthi Dias
Author

David R Crane
Author

Sara Hui
Author

Sameer Somanath
Author

Rob Hammond
Author

Alexander Middleditch
Author

David Crane
Author

Stuart Cleland
Author

David Brealey
Author

Sohail Bampoe
Author

Ana Gutierrez del Arroyo
Author

Robert Stephens
Author

David Brealey
Author

Anna Reyes
Author

Rupert M Pearse
Author

Gareth Ackland
Author

Gladys Martir
Author

Tim Martin
Author

Chimverly Diaz
Author

Maria Fernandez
Author

Fatima Seidu
Author

Stuart Cleland
Author

Mari-Liis Pakats
Author

Gary Minto
Author

Natasha Wilmshurst
Author

Otto Mahr
Author

Debbie-Claire Affleck
Author

Neil MacDonald
Author

Tracy Ward
Author

Filipa Dos Santos
Author

Amaia Arrieta Garcia
Author

Ruzena Uddin
Author

Gavin Werrett
Author

Salma Begum
Author

Susan Cummins
Author

Rupert Pearse
Author

Alan Amber
Author

Emily Subhedar
Author

Andrew Biffen
Author

Yize Wan
Author

Stephen Boumphrey
Author

Akshaykumar Patel
Author

Elizabeth Cann
Author

Charlotte Eglinton
Author

Elaine Jones
Author

Memory Mwadeyi
Author

Sam Piesley
Author

Richard Cowan
Author

Julie Alderton
Author

Fiona Reed
Author

Joanne Smith
Author

Amy Turner
Author

Lorraine Madziva
Author

Abigail Patrick
Author

Penny Harris
Author

Harry Lang
Author

Alexander Middleditch
Author

Anthony Pickering
Author

Catherine O'Donovan
Author

Rebecca Houlihan
Author

Rosina Jarvis
Author

Andrew Shrimpton
Author

Toni Farmery
Author

Katy Tucker
Author

Danielle Davis
Author

Sameer Somanth
Author

Louise Duncan
Author

Helen Melsom
Author

Sarah Clark
Author

Melanie Kent
Author

Michelle Wood
Author

Ami Laidlaw
Author

Tracy Matheson-Smith
Author

Kathryn Potts
Author

Andrea Kay
Author

Stefanie Hobson
Author

John Sear
Author

Vikas Kapil
Author

Andrew Archbold
Author

Matt Wilson
Author

Drilona Dndrejaj
Author

Dennis Ly
Author

Akshaykumar Patel
Author

Toby Richards
Author

Simon Finney
Author

Steve Harris
Author
