Peri-treatment of SGLT-2 Inhibitor on Myocardial Infarct Size and Remodeling Index in Patients With Acute Myocardial Infarction and High Risk of Heart Failure Undergoing Percutaneous Coronary Intervention (PRESTIGE-AMI)

Peri-tREatment of SGLT-2 Inhibitor on Myocardial Infarct Size and Remodeling Index Measured by Cardiac maGnetic rEsonance Imaging in Patients With Acute Myocardial Infarction and High Risk of Heart Failure Undergoing Percutaneous Coronary Intervention

We aimed to identify whether SGLT-2 inhibitor administration before and after coronary intervention is effective in reducing the size of infarction and myocardial remodeling in patients with acute myocardial infarction (AMI) and high risk of heart failure, and its mechanism. For this reason, we compared cardiac magnetic resonance imaging (CMR) parameters and clinical outcomes between the SGLT-2 inhibitor group and the control group to confirm the efficacy and safety of SGLT-2 inhibitors.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Acute Myocardial Infarction
• Intervention / Treatment: Drug: SGLT2 inhibitor; Other: Control

Detailed Description

After the introduction of percutaneous coronary intervention (PCI) as a method to normalize blood flow in the treatment of coronary artery disease, not only the technical aspects of coronary intervention but also the devices and medications have been improved over the past 30 years. However, despite these advances, morbidity, and mortality of AMI are still high. In particular, in patients with ST-segment elevation MI (STEMI), the 1-year mortality rate and hospitalization rate due to heart failure are 10%, and 22%, respectively. Accordingly, various efforts are being made to improve the prognosis of AMI and to reduce the infarct size, which is a major prognostic factor. The most effective method for achieving this goal to early and successful revascularization by PCI. However, restoring blood flow, which is a prerequisite for relieving ischemia, can paradoxically cause damage to the myocardium and death of the myocardium by itself. This phenomenon is called myocardial reperfusion injury. Several pharmacological and mechanical treatments targeting this phenomenon have been studied, and the experimental and small-scale clinical trials have been shown to have the effect of reducing infarct size and relieving myocardium.4 However, to date, large-scale clinical trials have not demonstrated clinical benefits.

SGLT-2 inhibitors are developed to lower blood sugar and treat type 2 diabetes mellitus (DM) by inhibiting Sodium glucose co-transporter-2 in proximal renal tubule, releasing glucose into the urine and preventing reabsorption. However, SGLT-2 inhibitors are known to have an effect on lowering cardiovascular events in addition to lowering blood sugar. In three large-scale, multicenter, randomized trials to evaluate the effects of SGLT-2 in type 2 diabetic patients, the combined outcome consisting of cardiac death or readmission due to heart failure was significantly lowered compared to the placebo group. In particular, DECLARE-TIMI 58 trial confirmed that this effect was consistent regardless of the history of atherosclerotic cardiovascular disease or heart failure.8 In addition, DAPA-CKD trial showed that SGLT-2 inhibitor significantly reduced the composite outcome consisting of cardiovascular death or readmission due to heart failure as well as the kidney-related outcome compared to the placebo group in patients with chronic kidney disease regardless of type 2 DM. Similarly, EMPEROR-Reduced and DAPA-HF trials consistently demonstrated that SGLT-2 inhibitor was associated with significantly lower risk of a composite of cardiovascular death or worsening heart failure in patients with heart failure with reduced ejection fraction. Therefore, the current guideline recommended the use of SGLT-2 inhibitor in patients with heart failure with reduced ejection fraction, with a conjunction of goal-directed medical therapy. Nevertheless, the mechanism that can explain this has been extensively investigated, but it is not clear yet. Several potential hypotheses have been proposed as mechanisms such as increased natriuresis, decreased blood pressure, decreased inflammation, and decreased reactive oxidative stress. In this regard, it is anticipated that the use of SGLT-2 inhibitors will benefit even in patients with AMI and high risk of heart failure in both acute and chronic phases.

Therefore, we aimed to identify whether SGLT-2 inhibitor administration before and after coronary intervention is effective in reducing the size of infarction and myocardial remodeling in patients with AMI and high risk of heart failure, and its mechanism. For this reason, we compared CMR parameters and clinical outcomes between the SGLT-2 inhibitor group and the control group to confirm the efficacy and safety of SGLT-2 inhibitors.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Ki Hong Choi, MD; Phone Number: 82-2-3410-6653; Email: cardiokh@gmail.com
• Study Contact Backup: Name: Young Bin Song, MD, PhD; Phone Number: 82-2-3410-1246; Email: youngbin.song@gmail.com

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Recruiting
    • Samsung Medical Center
    • Contact: Ki Hong Choi, MD; Phone Number: 82-2-3410-3419; Email: cardiokh@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1) Subject must be at least 18 years of age 2) Subject is able to verbally confirm understandings of risks, benefits and treatment alternatives of receiving SGLT-2 inhibitor and he/she or his/her legally authorized representative provides written informed consent prior to any study related procedure 3) Diagnosis of Type 1 myocardial infarction (MI) (ST-segment elevation MI [STEMI] or Non-ST-segment elevation MI [NSTEMI]) i) Detection of a rise and/or fall of cardiac troponin values with at least 1 value above the 99th percentile upper reference limit ii) Symptoms or electrocardiographic changes suggesting myocardial ischemia 4) High risk of heart failure (at least one of the two criteria below are met) i) Left ventricular ejection fraction < 50% ii) Symptoms or signs of pulmonary congestion requiring treatment

Exclusion Criteria:

• 1) Target lesion is not suitable for PCI by operator's decision 2) Patients requiring cardiopulmonary resuscitation due to cardiac arrest before randomization 3) Rescue PCI after thrombolysis or facilitated PCI 4) Previous MI 5) Previous history of heart failure 6) Patients who have been taking SGLT-2 inhibitor 7) Patients with glomerular filtration rate < 30ml/min/1.73m2 or on dialysis 8) Type 1 diabetes mellitus (DM) 9) Known hypersensitivity or contraindications to study medications (SGLT-2 inhibitor) 10) Pregnant or lactating women 11) Non-cardiac co-morbid conditions are present with life expectancy <1 year or that may result in protocol non-compliance (per site investigator's medical judgment)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SGLT-2 inhibitor; The SGLT-2 inhibitor group will receive SGLT-2 inhibitor once daily until the end of the study period.	Drug: SGLT2 inhibitor; In patients with AMI and high risk of heart failure, 1:1 randomization will be performed to either SGLT2 inhibitor or control group.
Placebo Comparator: Control; The control group will not receive any additional drugs.	Other: Control; In patients with AMI and high risk of heart failure, 1:1 randomization will be performed to either SGLT2 inhibitor or control group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Myocardial infract size (IS)	IS measured using CMR	at 6-month follow-up
∆Left ventricular end-systolic volume	Difference of left ventricular end-systolic volume measured by CMR	Between index hospitalization and 6-month follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute kidney injury	According to KDIGO guideline	Within 3 days after index PCI
Myocardial IS	IS measured using CMR	Within 3 days after index PCI
Microvascular obstruction (MVO)	MVO measured using CMR	Within 3 days after index PCI
IS	measured by peak cardiac enzyme	Within 3 days after index PCI
∆left ventricular end-diastolic volume	Difference of left ventricular end-diastolic volume measured using CMR	Between index hospitalization and 6-month follow-up
∆left ventricular ejection fraction	Difference of left ventricular ejection fraction measured using CMR	Between index hospitalization and 6-month follow-up
LV adverse remodeling	measured by CMR	Between index hospitalization and 6-month follow-up
LV reverse remodeling	measured by CMR	Between index hospitalization and 6-month follow-up
MVO	measured using CMR	at 6-month follow-up
Changes of NT-proBNP level	Difference of NT-proBNP	Between index hospitalization and 6-month follow-up
Estimated glomerular filtration rate	Kidney function	6 months after index PCI
All-cause death	All-cause death during follow-up	12 months after index PCI
Cardiovascular death	Cardiovascular death during follow-up	12 months after index PCI
MI	MI during follow-up	12 months after index PCI
Repeat revascularization	Repeat revascularization during follow-up	12 months after index PCI
Re-hospitalization due to heart failure	Re-hospitalization due to heart failure during follow-up	12 months after index PCI
Re-hospitalization due to cardiac cause	Re-hospitalization due to cardiac cause during follow-up	12 months after index PCI
Cerebrovascular events	ischemic or hemorrhagic stroke during follow-up	12 months after index PCI
Cardiovascular death, myocardial infarction, cerebrovascular events, stent thrombosis, and re-hospitalization due to cardiac cause	MACE	12 months after index PCI
Cardiovascular death, or re-hospitalization due to cardiac cause	cardiovascular death or re-hospitalization due to cardiac cause	12 months after index PCI

Collaborators and Investigators

• Sponsor: Samsung Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2021
• Primary Completion (Estimated): August 31, 2025
• Study Completion (Estimated): December 30, 2025

Study Registration Dates

• First Submitted: May 19, 2021
• First Submitted That Met QC Criteria: May 19, 2021
• First Posted (Actual): May 24, 2021

Study Record Updates

• Last Update Posted (Actual): June 26, 2025
• Last Update Submitted That Met QC Criteria: June 22, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Percutaneous Coronary Intervention; Infarct size; Cardiac Magnetic Resonance Imaging
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Necrosis; Myocardial Ischemia; Ischemia; Heart Failure; Myocardial Infarction; Infarction; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Sodium-Glucose Transporter 2 Inhibitors
• Other Study ID Numbers: PRESTIGE-AMI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The data, analytic methods, and study materials will not be made available to other researchers for purposes of reproducing the results or replicating the procedure.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No