Rationale and Design of the IMPROVE Trial: A Multicenter, Randomized, Controlled, Open-label, Blinded-endpoint Trial Assessing the Efficacy of Remote Ischemic Conditioning in Patients Undergoing Off-Pump Coronary Artery Bypass Grafting

Overview

Journal Adv Ther

Date 2024 Apr 14

PMID 38616242

Authors

Yang Yan

Changying Zhao

Jialan Niu

Pengyun Yan

Jing Li

Duolao Wang

Guoliang Li

Affiliations

Soon will be listed here.

Abstract

Introduction: Despite the appearance of off-pump coronary artery bypass grafting (CABG), ischemia-reperfusion injury (IRI) in the perioperative period still arouses concerns of clinicians. Remote ischemic conditioning (RIC) is the process of repeated ischemia and reperfusion in the peripheral vessels, which is proven to reduce IRI in vital organs. However, the effect of RIC in patients undergoing off-pump CABG is still unclear.

Methods: This IMPROVE trial is a national, multicenter, randomized, controlled, open-label, blinded-endpoint clinical trial designed to assess whether RIC intervention can improve short-term prognosis of patients undergoing off-pump CABG. It plans to enroll 648 patients who will be randomly assigned into a RIC group or control group. Patients in the RIC group will receive four cycles of 5 min of pressurization (about 200 mmHg) and 5 min of rest in the 3 days before and 7 days after the surgery.

Planned Outcomes: The primary outcome is the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) within the 3-month follow-up. MACCE is defined as all-cause death, myocardial infarction, stroke, and coronary revascularization surgery.

Clinical Trial Registration: NCT06141525 (ClinicalTrials.gov).

References

Doenst T, Haverich A, Serruys P, Bonow R, Kappetein P, Falk V . PCI and CABG for Treating Stable Coronary Artery Disease: JACC Review Topic of the Week. J Am Coll Cardiol. 2019; 73(8):964-976. DOI: 10.1016/j.jacc.2018.11.053. View

Besch G, Perrotti A, Salomon du Mont L, Puyraveau M, Ben-Said X, Baltres M . Impact of intravenous exenatide infusion for perioperative blood glucose control on myocardial ischemia-reperfusion injuries after coronary artery bypass graft surgery: sub study of the phase II/III ExSTRESS randomized trial. Cardiovasc Diabetol. 2018; 17(1):140. PMC: 6211400. DOI: 10.1186/s12933-018-0784-y. View

Kamenshchikov N, Mandel I, Podoksenov Y, Svirko Y, Lomivorotov V, Mikheev S . Nitric oxide provides myocardial protection when added to the cardiopulmonary bypass circuit during cardiac surgery: Randomized trial. J Thorac Cardiovasc Surg. 2018; 157(6):2328-2336.e1. DOI: 10.1016/j.jtcvs.2018.08.117. View

Lemoine S, Zhu L, Gerard J, Hanouz J . Sevoflurane-induced cardioprotection in coronary artery bypass graft surgery: Randomised trial with clinical and ex-vivo endpoints. Anaesth Crit Care Pain Med. 2017; 37(3):217-223. DOI: 10.1016/j.accpm.2017.05.009. View

Wang J, Toan S, Zhou H . New insights into the role of mitochondria in cardiac microvascular ischemia/reperfusion injury. Angiogenesis. 2020; 23(3):299-314. DOI: 10.1007/s10456-020-09720-2. View

de Waard D, Fagan A, Minnaar C, Horne D . Management of patients after coronary artery bypass grafting surgery: a guide for primary care practitioners. CMAJ. 2021; 193(19):E689-E694. PMC: 8157999. DOI: 10.1503/cmaj.191108. View

Shaefi S, Mittel A, Loberman D, Ramakrishna H . Off-Pump Versus On-Pump Coronary Artery Bypass Grafting-A Systematic Review and Analysis of Clinical Outcomes. J Cardiothorac Vasc Anesth. 2018; 33(1):232-244. DOI: 10.1053/j.jvca.2018.04.012. View

Ofoegbu C, Manganyi R . Off-Pump Coronary Artery Bypass Grafting; is it Still Relevant?. Curr Cardiol Rev. 2021; 18(2):e271021197431. PMC: 9413736. DOI: 10.2174/1573403X17666211027141043. View

Benedetto U, Altman D, Gerry S, Gray A, Lees B, Flather M . Off-pump versus on-pump coronary artery bypass grafting: Insights from the Arterial Revascularization Trial. J Thorac Cardiovasc Surg. 2018; 155(4):1545-1553.e7. DOI: 10.1016/j.jtcvs.2017.10.135. View

10.

Cour M, Lecour S . Remote ischaemic conditioning: in search of a suitable match. Nat Rev Cardiol. 2019; 16(12):704-705. DOI: 10.1038/s41569-019-0296-9. View

11.

Kharbanda R, Mortensen U, White P, Kristiansen S, Schmidt M, Hoschtitzky J . Transient limb ischemia induces remote ischemic preconditioning in vivo. Circulation. 2002; 106(23):2881-3. DOI: 10.1161/01.cir.0000043806.51912.9b. View

12.

Pickard J, Davidson S, Hausenloy D, Yellon D . Co-dependence of the neural and humoral pathways in the mechanism of remote ischemic conditioning. Basic Res Cardiol. 2016; 111(4):50. PMC: 4919370. DOI: 10.1007/s00395-016-0568-z. View

13.

Aimo A, Borrelli C, Giannoni A, Pastormerlo L, Barison A, Mirizzi G . Cardioprotection by remote ischemic conditioning: Mechanisms and clinical evidences. World J Cardiol. 2015; 7(10):621-32. PMC: 4620073. DOI: 10.4330/wjc.v7.i10.621. View

14.

Kloner R, Shi J, Dai W, Carreno J, Zhao L . Remote Ischemic Conditioning in Acute Myocardial Infarction and Shock States. J Cardiovasc Pharmacol Ther. 2019; 25(2):103-109. DOI: 10.1177/1074248419892603. View

15.

Saccaro L, Aimo A, Emdin M, Pico F . Remote Ischemic Conditioning in Ischemic Stroke and Myocardial Infarction: Similarities and Differences. Front Neurol. 2021; 12:716316. PMC: 8576053. DOI: 10.3389/fneur.2021.716316. View

16.

Gill R, Kuriakose R, Gertz Z, Salloum F, Xi L, Kukreja R . Remote ischemic preconditioning for myocardial protection: update on mechanisms and clinical relevance. Mol Cell Biochem. 2015; 402(1-2):41-9. DOI: 10.1007/s11010-014-2312-z. View

17.

Bell R, Basalay M, Botker H, Kalkhoran S, Carr R, Cunningham J . Remote ischaemic conditioning: defining critical criteria for success-report from the 11th Hatter Cardiovascular Workshop. Basic Res Cardiol. 2022; 117(1):39. PMC: 9377667. DOI: 10.1007/s00395-022-00947-2. View

18.

Ho A, Chong J, Ong M, Hausenloy D . Remote Ischemic Conditioning in Emergency Medicine-Clinical Frontiers and Research Opportunities. Shock. 2020; 53(3):269-276. DOI: 10.1097/SHK.0000000000001362. View

19.

Moscarelli M, Fiorentino F, Suleiman M, Emanueli C, Reeves B, Punjabi P . Remote ischaemic preconditioning in isolated aortic valve and coronary artery bypass surgery: a randomized trial†. Eur J Cardiothorac Surg. 2018; 55(5):905-912. PMC: 6477640. DOI: 10.1093/ejcts/ezy404. View

20.

Ney J, Hoffmann K, Meybohm P, Goetzenich A, Kraemer S, Benstom C . Remote Ischemic Preconditioning Does Not Affect the Release of Humoral Factors in Propofol-Anesthetized Cardiac Surgery Patients: A Secondary Analysis of the RIPHeart Study. Int J Mol Sci. 2018; 19(4). PMC: 5979505. DOI: 10.3390/ijms19041094. View