Cardiology · Medical Literature
SGLT2 Inhibitor on Infarct Size and LV Remodeling by CMR in Patients With AMI.
Abstract
Although recent large-scale randomized trials have demonstrated that sodium-glucose cotransporter 2 (SGLT2) inhibitors following acute myocardial infarction (AMI) are safe, the mechanisms underlying their potential cardioprotective effects remain poorly understood. The aim of this study was to evaluate the effects of SGLT2 inhibitor therapy on myocardial injury and left ventricular (LV) remodeling in AMI patients undergoing percutaneous coronary intervention (PCI), using cardiac magnetic resonance imaging (CMR). In this prospective, open-label, randomized controlled trial, patients ≥18 years of age at high risk for heart failure after successful PCI for AMI were randomly assigned to receive empagliflozin 10 mg once daily or not. The primary endpoint was infarct size (% LV mass) assessed by CMR at 6-month follow-up. The coprimary endpoint was a difference in LV end-systolic volume measured by CMR between baseline and 6 months (ΔLV end-systolic volume). A total of 200 patients underwent randomization, with 100 assigned to the SGLT2 inhibitor group and 100 assigned to the control group. CMR assessments for 6 months were available for 169 patients (84.0%) of the total study population (89 patients in the SGLT2 inhibitor group and 80 patients in the control group). Compared with control, SGLT2 inhibition did not reduce infarct size (% LV mass) at 6-month follow-up (SGLT2 inhibitor vs control, 12.5% [8.5%-20.9%] vs 12.9% [5.0%-20.7%]; P = 0.92). There was no significant difference in ΔLV end-systolic volume between the 2 groups (SGLT2 inhibitor vs control, -3.3% [-19.7% to 13.6%] vs -6.8% [-23.4% to 10.6%]; P = 0.40). Among patients with AMI undergoing PCI who were at high risk for heart failure, SGLT2 inhibitor use did not reduce infarct size or facilitate reverse LV remodeling at 6 months as assessed by CMR. (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]; NCT04899479).
Clinical relevance
Despite the established cardiovascular mortality benefits of SGLT2 inhibitors in heart failure and high-risk populations, the mechanistic basis for any cardioprotective effect in the acute myocardial infarction (AMI) setting—specifically regarding myocardial salvage and structural remodeling—has remained poorly characterized. This RCT addresses a critical pathophysiological gap by using cardiac magnetic resonance imaging (CMR), the gold standard for infarct quantification and volumetric LV assessment, to rigorously evaluate empagliflozin's impact post-PCI in AMI patients at high risk for heart failure. The findings are immediately clinically relevant given the increasing real-world use of SGLT2 inhibitors early post-AMI extrapolated from large outcomes trials.
Key findings
1. No significant reduction in infarct size: Empagliflozin 10 mg daily did not reduce CMR-assessed infarct size (% LV mass) at 6 months compared to control (12.5% [IQR 8.5%–20.9%] vs. 12.9% [IQR 5.0%–20.7%]; P = 0.92). 2. No significant difference in LV reverse remodeling: The co-primary endpoint of change in LV end-systolic volume (ΔLVESV) from baseline to 6 months did not differ significantly between groups (SGLT2 inhibitor: −3.3% [IQR −19.7% to 13.6%] vs. control: −6.8% [IQR −23.4% to 10.6%]; P = 0.40). 3. Study population and design: This was a prospective, open-label, randomized controlled trial enrolling 200 patients (≥18 years) at high risk for heart failure following successful PCI for AMI, with 100 patients per arm. 4. CMR follow-up completion rate: Serial CMR data at 6 months were available for 169 of 200 randomized patients (84.0%), comprising 89 in the empagliflozin group and 80 in the control group, indicating adequate retention for a mechanistic imaging endpoint trial. 5. Primary drug and dose: The intervention was empagliflozin 10 mg once daily, initiated in the peri-PCI period, consistent with doses validated in the EMPEROR-Reduced and EMPA-REG OUTCOME trials. 6. Safety context: The study was conducted in the context of prior large-scale RCT data confirming the safety of SGLT2 inhibitors post-AMI, but this trial specifically interrogated cardioprotective mechanisms rather than clinical event rates—no superiority was demonstrated on either structural CMR endpoint.
Practice implications
Clinicians should not initiate empagliflozin post-AMI with the expectation of reducing infarct size or promoting reverse LV remodeling, as this CMR-based RCT found no benefit on either structural endpoint at 6 months in PCI-treated AMI patients at high heart failure risk. SGLT2 inhibitor therapy post-AMI should continue to be guided by established indications—namely, comorbid type 2 diabetes, chronic heart failure with reduced ejection fraction, or chronic kidney disease—rather than presumed acute cardioprotective effects on infarct biology. Future investigation should focus on identifying specific AMI subpopulations, optimal timing of initiation relative to reperfusion, and alternative mechanistic pathways (e.g., metabolic, anti-inflammatory, or microvascular) that may yet reveal differential benefit not captured by infarct size and LVESV at 6 months.