Impact of continuing renin-angiotensin-aldosterone system inhibitors before surgery on intraoperative hypotensive events: a secondary analysis of the STOP-or-NOT Trial.

BACKGROUND: The multicentre STOP-or-NOT trial has shown that continuation of renin-angiotensin-aldosterone inhibitors (RAASis) before major noncardiac surgery did not increase the rate of postoperative complications, but led to a higher incidence of intraoperative hypotension. However, the risk of intraoperative hypotension could vary significantly between patients. We evaluated whether there is heterogeneity in the risk of intraoperative hypotension among patients who continue vs those who discontinue RAASi therapy before major surgery. METHODS: We conducted a secondary analysis of the STOP-or-NOT trial. The primary outcome was intraoperative hypotension (defined as a mean arterial pressure <60 mm Hg) requiring vasopressor administration. We assessed for the presence of significant heterogeneity of treatment effect (HTE). When HTE was statistically significant, we estimated the conditional average treatment effect (CATE) using a machine learning approach. On the basis of CATE estimates, patients were stratified into three risk groups: high-risk (top 20%), low-risk (bottom 5%), and medium-risk (remaining 75%). RESULTS: Among 2007 patients, there was a statistically significant HTE for the risk of hypotension. Compared with the low-risk group, patients in the high-risk group (CATE risk difference, 0.172 [0.161-0.179]) were younger (62 vs 69 yr; P<0.001) and had a higher BMI (34 vs 27k m-2; P<0.001), lower baseline systolic blood pressure (133 vs 138 mm Hg; P<0.001), higher baseline haemoglobin (14.9 vs 12.2 g dl-1; P<0.001), and lower serum creatinine (76 vs 82 μM; P=0.003). CONCLUSIONS: Our analysis supports the existence of significant heterogeneity in the risk of intraoperative hypotension associated with the continuation of RAASi therapy before major noncardiac surgery. CLINICAL TRIAL REGISTRATION: NCT03374449.