Acute Myocardial Infarction, Heart Failure
Conditions
Keywords
Percutaneous Coronary Intervention, Infarct size, Cardiac Magnetic Resonance Imaging
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.
Interventions
DRUGSGLT2 inhibitor
In patients with AMI and high risk of heart failure, 1:1 randomization will be performed to either SGLT2 inhibitor or control group.
OTHERControl
In patients with AMI and high risk of heart failure, 1:1 randomization will be performed to either SGLT2 inhibitor or control group.
Sponsors
Samsung Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
This is an open-label study, therefore, no masking will be performed.
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).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Myocardial infract size (IS) | at 6-month follow-up | IS measured using CMR |
| ∆Left ventricular end-systolic volume | Between index hospitalization and 6-month follow-up | Difference of left ventricular end-systolic volume measured by CMR |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Microvascular obstruction (MVO) | Within 3 days after index PCI | MVO measured using CMR |
| IS | Within 3 days after index PCI | measured by peak cardiac enzyme |
| ∆left ventricular end-diastolic volume | Between index hospitalization and 6-month follow-up | Difference of left ventricular end-diastolic volume measured using CMR |
| ∆left ventricular ejection fraction | Between index hospitalization and 6-month follow-up | Difference of left ventricular ejection fraction measured using CMR |
| LV adverse remodeling | Between index hospitalization and 6-month follow-up | measured by CMR |
| LV reverse remodeling | Between index hospitalization and 6-month follow-up | measured by CMR |
| MVO | at 6-month follow-up | measured using CMR |
| Changes of NT-proBNP level | Between index hospitalization and 6-month follow-up | Difference of NT-proBNP |
| Estimated glomerular filtration rate | 6 months after index PCI | Kidney function |
| Acute kidney injury | Within 3 days after index PCI | According to KDIGO guideline |
| Cardiovascular death, or re-hospitalization due to cardiac cause | 12 months after index PCI | cardiovascular death or re-hospitalization due to cardiac cause |
| All-cause death | 12 months after index PCI | All-cause death during follow-up |
| Cardiovascular death | 12 months after index PCI | Cardiovascular death during follow-up |
| MI | 12 months after index PCI | MI during follow-up |
| Repeat revascularization | 12 months after index PCI | Repeat revascularization during follow-up |
| Re-hospitalization due to heart failure | 12 months after index PCI | Re-hospitalization due to heart failure during follow-up |
| Re-hospitalization due to cardiac cause | 12 months after index PCI | Re-hospitalization due to cardiac cause during follow-up |
| Cerebrovascular events | 12 months after index PCI | ischemic or hemorrhagic stroke during follow-up |
| Cardiovascular death, myocardial infarction, cerebrovascular events, stent thrombosis, and re-hospitalization due to cardiac cause | 12 months after index PCI | MACE |
| Myocardial IS | Within 3 days after index PCI | IS measured using CMR |
Countries
South Korea
Contacts
Primary ContactYoung Bin Song, MD, PhD
Backup ContactKi Hong Choi, MD
Outcome results
None listed