Clinical trial NCT04899479: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Acute Myocardial Infarction
Heart Failure
Keywords: Percutaneous Coronary Intervention
Infarct size
Cardiac Magnetic Resonance Imaging
Lead sponsor: Samsung Medical Center
Sponsor class: OTHER
First posted: 2021-05-24
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomization will be performed 1:1 between SGLT-2 inhibitor and control. Stratification will be done by DM and clinical presentation (STEMI vs. NSTEMI).
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Myocardial infract size (IS)
timeFrame: at 6-month follow-up
measure: ∆Left ventricular end-systolic volume
timeFrame: Between index hospitalization and 6-month follow-up
Secondary outcomes:
measure: Acute kidney injury
timeFrame: Within 3 days after index PCI
measure: Myocardial IS
timeFrame: Within 3 days after index PCI
measure: Microvascular obstruction (MVO)
timeFrame: Within 3 days after index PCI
measure: IS
timeFrame: Within 3 days after index PCI
measure: ∆left ventricular end-diastolic volume
timeFrame: Between index hospitalization and 6-month follow-up
measure: ∆left ventricular ejection fraction
timeFrame: Between index hospitalization and 6-month follow-up
measure: LV adverse remodeling
timeFrame: Between index hospitalization and 6-month follow-up
measure: LV reverse remodeling
timeFrame: Between index hospitalization and 6-month follow-up
measure: MVO
timeFrame: at 6-month follow-up
measure: Changes of NT-proBNP level
timeFrame: Between index hospitalization and 6-month follow-up
measure: Estimated glomerular filtration rate
timeFrame: 6 months after index PCI
measure: Cardiovascular death, MI, myocardial infarction, cerebrovascular events, stent thrombosis, and re-hospitalization due to cardiac cause
timeFrame: 12 months after index PCI
measure: Cardiovascular death, or re-hospitalization due to cardiac cause
timeFrame: 12 months after index PCI
measure: All-cause death
timeFrame: 12 months after index PCI
measure: Cardiovascular death
timeFrame: 12 months after index PCI
measure: MI
timeFrame: 12 months after index PCI
measure: Repeat revascularization
timeFrame: 12 months after index PCI
measure: Re-hospitalization due to heart failure
timeFrame: 12 months after index PCI
measure: Re-hospitalization due to cardiac cause
timeFrame: 12 months after index PCI
measure: Cerebrovascular events
timeFrame: 12 months after index PCI
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
References: