Withholding vs. Continuing Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers Before Non-cardiac Surgery in Older Patients: Study Protocol for a Multicenter Randomized Controlled Trial

Abstract

Background: Older hypertensive adults are at increased risk for postoperative morbidity and mortality. As first line antihypertensive drug therapy, angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) have many beneficial effects. However, the use of ACEIs/ARBs in the perioperative period remains controversial. This study aims to determine the effects of withholding vs. continuing ACEIs/ARBs before non-cardiac surgery on perioperative hypotension and postoperative outcomes in older patients.Methods: In this multicenter, randomized, double-blind, placebo-controlled trial, a total of 2036 patients aged 60–80 years undergoing non-cardiac surgical procedures will be randomly assigned, in a 1:1 ratio, to receive oral ACEIs/ARBs (the ACEIs/ARBs continued group) or inactive placebos (the ACEIs/ARBs withheld group) on the morning of surgery. For both groups, the ACEIs/ARBs will be continued from the first postoperative day. The primary outcome measure is the incidence of perioperative hypotensive events, defined as mean blood pressure (MBP) < 65 mmHg or ≥30% reduction in MBP from baseline during surgery and in a post-anesthesia care unit. The secondary outcomes include duration of perioperative hypotension, intraoperative use of fluids and vasopressors, hypotensive events within postoperative 3 days, and perioperative neurocognitive disorders, major adverse cardiocerebral events (a composite outcome of stroke, coma, myocardial infarction, heart block, and cardiac arrest), and mortality within 30 days after surgery.Discussion: The results of this trial will offer an evidence-based perioperative ACEIs/ARBs therapy for older hypertensive adults undergoing non-cardiac surgery.Study Registration: This study is approved by the Medical Ethics Committee of The First Affiliated Hospital of Soochow University (Approval No. 2020-077-1) and by the institutional ethics review board of each participating center. This protocol is registered at the Chinese Clinical Trials Registry (ChiCTR2000039376).

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

“…To our knowledge, only two multicentric trials (ongoing) are looking at the effect of continuing vs withholding of ACEIs/ARBs in patients undergoing non-cardiac surgery [ 11 , 16 ]. However, the protocol of our study differs from the other two protocols.…”

“…In contrast, our trial will evaluate the continuing vs withholding of ACEI/ARBs 24-36 h before non-cardiac surgery, similar to the retrospective VISION trial which also evaluated the withholding of the ACEIs/ARBs 24 h before surgery on major adverse outcomes [3]. The second ongoing multicentric study is published by Yang et al encompassing six Chinese centres which includes geriatric hypertensive patients (60-80 years), and their primary end-point is the incidence of perioperative hypotensive events in patients undergoing a general anaesthetic [16]; whereas our primary outcome is a composite outcome of allcause in-hospital/30-day mortality, major adverse cardiovascular and non-cardiovascular events in patients aged 18-70 years and undergoing surgery under both general and neuraxial anaesthesia. Thus, the result of our study is expected to add value to this important clinical conundrum.…”

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

“…Intraoperative fluids may be administered in order to minimize intraoperative hypotension under spinal anesthesia. Nevertheless, no strategy is effective in avoiding hypotension on their own and must be combined with the prudent use of vasopressors [34].…”

Protocol for development and validation of a prediction model for post-induction hypotension in elderly patients undergoing non-cardiac surgery: a prospective cohort study

“…Hypotension is defined as either a 30% reduction in mean arterial pressure (MAP) from baseline or absolute MAP ≤65 mm Hg. Dual definitions for diagnosis of hypotension (either a relative reduction in MAP or an absolute threshold of MAP) have been used in many recent studies 20–25…”