The effect of continuing versus withholding angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers on mortality and major adverse cardiovascular events in hypertensive patients undergoing elective non-cardiac surgery: study protocol for a multi-centric open-label randomised controlled trial

Abstract

Background Angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) are commonly prescribed to patients with hypertension. These drugs are cardioprotective in addition to their blood pressure-lowering effects. However, it is debatable whether hypertensive patients who present for non-cardiac surgery should continue or discontinue these drugs preoperatively. Continuing the drugs entails the risk of perioperative refractory hypotension and/or angioneurotic oedema, while discontinuing the drugs entails the risk of rebound hypertension and myocardial ischaemia. The aim of this study is to evaluate the effect of continuation vs withholding of ACEIs/ARBs on mortality and other major outcomes in hypertensive patients undergoing elective non-cardiac surgery. Methods The continuing vs withholding of ACEIs/ARBs in patients undergoing non-cardiac surgery is a prospective, multi-centric, open-label randomised controlled trial. Two thousand one hundred hypertensive patients receiving ACEIs/ARBs and planned for elective non-cardiac surgery will be enrolled. They will be randomised to either continue the ACEIs/ARBs including on the day of surgery (group A) or to withhold it 24–36 h before surgery (group B). The primary endpoint will be the difference in the composite outcome of all-cause in-hospital/30-day mortality and major adverse cardiovascular and non-cardiovascular events. Secondary endpoints will be to evaluate the differences in perioperative hypotension, angioneurotic oedema, myocardial injury, ICU and hospital stay. The impact of the continuation vs withholding of the ACEIs/ARBs on the incidence of case cancellation will also be studied. Discussion The results of this trial should provide sufficient evidence on whether to continue or withhold ACEIs/ARBs before major non-cardiac surgery. Trial registration Clinical Trials Registry of India CTRI/2021/01/030199. Registered on 4 January 2021

Candidate Kidney Protective Strategies for Patients Undergoing Major Abdominal Surgery: A Secondary Analysis of the RELIEF Trial Cohort

“…Three large, randomized trials addressing the effect of various perioperative management strategies of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker medication on important renal and other outcomes are ongoing or recently completed. 44–46 The modest association between nadir hemoglobin concentration on postoperative day 1 and AKI in model 2 is consistent with previous data showing an association between postoperative bleeding and AKI in patients undergoing noncardiac surgery. 10 However, the POISE-3 trial of tranexamic acid versus placebo in patients undergoing noncardiac surgery found no effect of this strategy on AKI despite reducing both major bleeding and the proportion of patients administered a perioperative packed red cell transfusion, highlighting the complexity of the anemia–AKI association.…”

Study on Perioperative Management of Blood Pressure and Effects of Anaesthesia in Hypertensive Patients Undergoing General & Orthopaedic Surgery

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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

“…Our data suggest that ongoing pragmatic multicentre trials examining the management of RAS inhibitors in patients age ≥18 yr undergoing noncardiac surgery should consider using natriuretic peptide biomarkers to refine interpretation of their data. 34 , 35 , 36 Because two large database studies in noncardiac 37 and cardiac surgery 38 have identified that failure to restart RAS inhibitors is strongly associated with excess morbidity and mortality, further work is required to establish whether serial NT-proBNP measurements can help guide recommencing this drug class. This is particularly relevant given that acute hypertension is independently associated with myocardial injury, 39 most likely through elevated preload causing stretch-induced cardiomyocyte stress.…”