SGLT2 Inhibitor Offers Kidney Protection and Reduces Heart Failure Risk After Acute Myocardial Infarction

When initiated shortly after an acute myocardial infarction, empagliflozin (Jardiance; Boehringer Ingelheim, Eli Lilly) not only offers significant kidney-protective benefits by stabilizing kidney function but also effectively reduces the risk of heart failure, all while maintaining a strong safety profile across a broad range of baseline kidney function levels, according to recent findings from the EMPACT-MI trial (NCT04509674).1

EMPACT-MI findings highlight empagliflozin's significant cardiovascular and kidney benefits.

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Previously, data on the cardiovascular-kidney effects and safety of empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, in patients who recently experienced an acute myocardial infarction were limited. Pivotal EMPACT-MI data presented at last fall’s 2024 European Society of Cardiology Congress evaluated whether SGLT2 inhibitor treatment had an impact on kidney health in this patient population.2

“That was the concern,” Deepak Bhatt, MD, MPH, MBA, director of Mount Sinai Heart, said in an interview with The American Journal of Managed Care® (AJMC®) at the conference. “What we found quite reassuringly, first of all, was that introducing SGLT2 inhibitors, specifically empagliflozin—though I think the results are generalizable to the class—that introduction of the SGLT2 inhibitor in this context was safe.”

Now, findings from the secondary analysis of this pivotal trial shed new light on empagliflozin’s impact on kidney function and heart failure outcomes.1 The large-scale, double-blind, multicenter clinical trial randomized 6522 patients with acute myocardial infarction and an elevated risk for heart failure to either empagliflozin or placebo.

Kidney-Protective Effects Observed

The analysis revealed evidence of empagliflozin's kidney-protective effects. At baseline, the mean (SD) estimated glomerular filtration rate (eGFR) was 76.1 (19.9) mL/min/1.73 m2. While an initial, transient decline in eGFR was observed with empagliflozin—a known hemodynamic effect of SGLT2 inhibitors and considered nonharmful in the long term—this decline fully recovered. By 24 months, eGFR remained stable in the empagliflozin group, whereas it continued to decline in the placebo group (P = .01).

This finding is particularly significant as kidney function decline is common among patients with prior cardiovascular events, the authors emphasized. The stability in eGFR with empagliflozin in this vulnerable population further supports its use. The observed patterns in eGFR change were consistent across different baseline kidney function levels and the use of other common heart and kidney medications.

Reduced Heart Failure Outcomes Across Kidney Function

Beyond kidney protection, empagliflozin demonstrated a clear benefit in reducing the total adverse events of heart failure or all-cause mortality. Importantly, this reduction was consistent regardless of the patient's baseline kidney function (Pinteraction ​= .30). This reinforces previous findings from EMPACT-MI, which was the first study to show a benefit in heart failure risk reduction specifically in patients with acute myocardial infarction. Given that patients with chronic kidney disease are at an especially high risk of heart failure, the authors highlighted that therapies that can mitigate this burden, like empagliflozin, hold substantial clinical importance.

Safe for Early Initiation Post Myocardial Infarction

A critical aspect of the findings relates to the safety of initiating empagliflozin therapy shortly after an acute myocardial infarction. The trial showed that 30-day adverse event rates were similar between the empagliflozin and placebo groups, and these rates remained consistent across various baseline kidney function levels, blood pressure readings, and the use of concomitant therapies.

Physicians often express concerns about starting SGLT2 inhibitors in patients with acute myocardial infarction due to the potential for an initial eGFR decrease, the authors noted, especially given the vulnerability of this population to contrast exposure and acute kidney injury. However, this demonstrated that the acute treatment effect on eGFR with empagliflozin was similar to placebo and that overall safety was maintained. Notably, rates of acute renal failure were even numerically lower in the empagliflozin group, particularly in vulnerable subgroups with lower baseline eGFR or blood pressure.

Clinical Implications and Future Directions

These results have significant implications for clinical practice, suggesting that empagliflozin can be safely and effectively initiated during or early after hospitalization for acute myocardial infarction. SGLT2 inhibitors are underutilized, especially in primary care settings.3 The dual benefits of kidney protection and heart failure reduction exhibited by empagliflozin across a spectrum of kidney function levels indicate its value to post myocardial infarction care.1

The study acknowledges certain limitations, including the availability of longitudinal eGFR data from only a subset of countries and the relatively small sample size for patients with very low (< 30 mL/min/1.73 m2). Additionally, EMPACT-MI was not specifically powered for kidney outcomes. Future research is needed to assess the benefits in patients with acute myocardial infarction who are not at an especially high risk for heart failure, as this remains an understudied group.

“SGLT2 inhibitors are underused in clinical practice," Bhatt said in a statement.4 "These data provide reassurance of the safety of using this class of drugs when indicated—even in patients after a recent heart attack and if the kidney function is impaired.”

References

1. Aggarwal R, Bhatt DL, Hernandez AF, et al. Secondary analysis of the EMPACT-MI trial reveals cardiovascular-kidney efficacy and safety of empagliflozin after acute myocardial infarction. Nat Cardiovasc Res. 2025;4(6):761-772. doi:10.1038/s44161-025-00657-7

2. Grossi G. Dr Deepak Bhatt: empagliflozin shows no increased kidney risk after acute myocardial infarction. AJMC. September 2, 2024. Accessed July 9, 2025. https://www.ajmc.com/view/dr-deepak-bhatt-empagliflozin-shows-no-increased-kidney-risk-after-acute-myocardial-infarction

3. Grossi G. SGLT2 inhibitors show renal benefits in HF and CKD as prescribers target uptake gaps. AJMC. April 15, 2025. Accessed July 9, 2025. https://www.ajmc.com/view/sglt2-inhibitors-show-renal-benefits-in-hf-and-ckd-as-prescribers-target-uptake-gaps

4. SGLT2 inhibitor empagliflozin treatment stabilizes kidney function in patients who have had a heart attack. News release. Mount Sinai. June 13, 2025. Accessed July 9, 2025. https://www.mountsinai.org/about/newsroom/2025/sglt2-inhibitor-empagliflozin-treatment-stabilizes-kidney-function-in-patients-who-have-had-a-heart-attack