Preoperative N-terminal pro-B-type natriuretic peptide and myocardial injury after stopping or continuing renin–angiotensin system inhibitors in noncardiac surgery: a prespecified analysis of a phase 2 randomised controlled multicentre trial
Ana Gutierrez del Arroyo, Akshaykumar Patel, Tom Abbott, Salma Begum, Priyanthi Dias, Sameer Somanath, Alexander Middleditch, Stuart Cleland, David Brealey, Rupert M. Pearse, Gareth L. Ackland, Gareth L. Ackland, Tim Martin, Maria Fernandez, Fatima Seidu, Mari-Liis Pakats, Otto Mahr, Neil MacDonald, Filipa Santos, Amaia Arrieta Garcia, Ruzena Uddin, Salma Begum, Rupert M. Pearse, Emily Subhedar, Yize I. Wan, Akshaykumar Patel, Tasnin Shahid, Mevan Gooneratne, Charlotte Trainer, Bethan Griffiths, Steven Dunkley, Shaun M. May, Sophie Walker, Alexander J. Fowler, Tim Stephens, Mônica Amorim de Oliveira, Marta Januszewska, Edyta Niebrzegowska, Vanessa Teixeira do Amaral, Jamila Kassam, Sophie Young, Shanaz Ahmad, Jan Whalley, Ryan W. Haines, Sara Hui, Rob Hammond, David Crane, David Brealey, Sohail Bampoe, Robert Stephens, Anna Reyes, Gladys Martir, C. Rios Diaz, Stuart Cleland, Gary Minto, Natasha Wilmshurst, Debbie-Claire Affleck, Tracy Ward, G. Werrett, Susan K. Cummins, Alan Amber, Andrew Biffen, Stephen Boumphrey, E. Van Cann, Charlotte Eglinton, Elaine Jones, Memory Mwadeyi, Sam Piesley, Richard Cowan, Julie Alderton, Fiona Reed, Joanne Smith, Amy S. Turner, Lorraine Madziva, Abigail Patrick, Penny Harris, Harry Lang, Alexander Middleditch, Anthony E. Pickering, Catherine O’Donovan, Rebecca Houlihan, Rosina Jarvis, Andrew Shrimpton, Toni Farmery, Katy Tucker, Danielle Davis, Sameer Somanth, Louise Duncan, H Melsom, Sarah L. Clark, Melanie Kent, Michelle A. Wood, A Laidlaw, Tracy Matheson-Smith, Kathryn Potts, Andrea Kay, Stefanie Hobson, John W. Sear, Vikas Kapil, Andrew Archbold
Abstract
BackgroundPatients with elevated preoperative plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP >100 pg ml−1) experience more complications after noncardiac surgery. Individuals prescribed renin–angiotensin system (RAS) inhibitors for cardiometabolic disease are at particular risk of perioperative myocardial injury and complications. We hypothesised that stopping RAS inhibitors before surgery increases the risk of perioperative myocardial injury, depending on preoperative risk stratified by plasma NT-proBNP concentrations.MethodsIn a preplanned analysis of a phase 2a trial in six UK centres, patients ≥60 yr old undergoing elective noncardiac surgery were randomly assigned either to stop or continue RAS inhibitors before surgery. The pharmacokinetic profile of individual RAS inhibitors determined for how long they were stopped before surgery. The primary outcome, masked to investigators, clinicians, and patients, was myocardial injury (plasma high-sensitivity troponin-T ≥15 ng L−1 or a ≥5 ng L−1 increase, when preoperative high-sensitivity troponin-T ≥15 ng L−1) within 48 h after surgery. The co-exposures of interest were preoperative plasma NT-proBNP (< or >100 pg ml −1) and stopping or continuing RAS inhibitors.ResultsOf 241 participants, 101 (41.9%; mean age 71 [7] yr; 48% females) had preoperative NT-proBNP >100 pg ml −1 (median 339 [160–833] pg ml−1), of whom 9/101 (8.9%) had a formal diagnosis of cardiac failure. Myocardial injury occurred in 63/101 (62.4%) subjects with NT-proBNP >100 pg ml−1, compared with 45/140 (32.1%) subjects with NT-proBNP <100 pg ml −1 {odds ratio (OR) 3.50 (95% confidence interval [CI] 2.05–5.99); P<0.0001}. For subjects with preoperative NT-proBNP <100 pg ml−1, 30/75 (40%) who stopped RAS inhibitors had myocardial injury, compared with 15/65 (23.1%) who continued RAS inhibitors (OR for stopping 2.22 [95% CI 1.06–4.65]; P=0.03). For preoperative NT-proBNP >100 pg ml−1, myocardial injury rates were similar regardless of stopping (62.2%) or continuing (62.5%) RAS inhibitors (OR for stopping 0.98 [95% CI 0.44–2.22]).ConclusionsStopping renin-angiotensin system inhibitors in lower-risk patients (preoperative NT-proBNP <100 pg ml −1) increased the likelihood of myocardial injury before noncardiac surgery.