Preoperative Cardiovascular Risk and Postoperative Outcomes by Renin-Angiotensin System Inhibitor Use

Importance: The STOP-or-NOT randomized clinical trial compared the outcomes of continuing vs discontinuing renin-angiotensin system inhibitors (RASi) prior to major noncardiac surgery and found no difference in the postoperative risk of death or major complications, but it remains unclear whether preoperative cardiovascular risk stratification influences the response to this intervention. This post hoc analysis explores whether preoperative cardiovascular risk stratification affects the outcomes in patients who continue vs discontinue RASi use before major surgery. Objective: To evaluate whether preoperative cardiovascular risk stratification affects the strategy of RASi management before major noncardiac surgery. Design, Setting, and Participants: This is a post hoc analysis of the multicenter STOP-or-NOT randomized clinical trial, conducted across 40 hospitals in France between January 2018 and April 2023, with follow-up for 28 days postoperatively. Data analysis was performed from September 2024 to January 2025. The participants were patients who had been treated with RASi for at least 3 months and were scheduled for major noncardiac surgery. Intervention: Patients were randomized to either continue RASi until the day of surgery or to discontinue RASi 48 hours prior to surgery. Main Outcomes and Measures: The primary outcome was a composite of all-cause mortality and major postoperative complications. Secondary outcomes were major adverse cardiovascular events and acute kidney injury. Cardiovascular risk stratification was assessed with the Revised Cardiac Risk Index (RCRI), American University of Beirut (AUB)-HAS2 Cardiovascular Risk Index, and systolic blood pressure prior to randomization. Results: Among the 2222 patients (median [IQR] age, 68 [61-73] years; 771 [35%] female), 1107 were randomized to RASi continuation and 1115 were randomized to RASi discontinuation. Using the RCRI, 592 patients were categorized as low risk (0 points), 1095 as intermediate-low risk (1 point), 418 as intermediate-high risk (2 points), and 117 as high risk (≥3 points). Using the AUB-HAS2 Cardiac Risk Index, 1049 patients were categorized as low risk (0 points), 727 as intermediate-low risk (1 point), 333 as intermediate-high risk (2 points), and 113 as high risk (≥3 points). A total of 2132 patients were split into 4 quartiles of preoperative systolic blood pressure. The risk of postoperative complications and major adverse cardiovascular events varied with RCRI score. However, a strategy of RASi continuation vs discontinuation was not associated with a higher risk of postoperative complications. Conclusions: This study found that preoperative cardiovascular risk did not affect patient outcomes with respect to the strategy of continuing vs discontinuing RASi before major noncardiac surgery, suggesting that the decision to continue or discontinue RASi should not be influenced by a patient's preoperative cardiovascular risk assessment. Trial Registration: ClinicalTrials.gov Identifier: NCT03374449.