Survivors of ST-elevation myocardial infarction (STEMI) continue to face appreciable risks of hospitalization for heart failure and acute kidney injury (AKI), even in the era of prompt primary percutaneous coronary intervention (PCI). Sodium–glucose cotransporter-2 inhibitors (SGLT2i) deliver proven cardio–renal benefits in chronic heart failure and chronic kidney disease (CKD); however, the safety profile of these agents when initiating administration during the index STEMI admission remains poorly characterized. This clinical review summarizes contemporary evidence on the hemodynamic and renal safety of initiating SGLT2i therapy 24–72 h after PCI in patients with STEMI and provides a pragmatic, evidence-informed bedside framework, supported by randomized controlled trials (RCTs) and mechanistic and observational data from January 2018 to July 2025. Trial eligibility criteria and safety endpoints were extracted qualitatively; no formal meta-analysis was performed. Among at least 11,221 participants, early SGLT2i initiation was well tolerated: rates of hypotension, volume depletion, AKI, and diabetic ketoacidosis (DKA) were comparable to placebo. The characteristic 3–6 mL/min/1.73 m2 decline in estimated glomerular filtration rate (eGFR) represented a reversible tubuloglomerular feedback (TGF) adjustment rather than nephrotoxicity. Mechanistic studies attribute these findings to mild natriuresis without sympathetic activation and to afferent arteriolar vasoconstriction, which lowers intraglomerular pressure. Synthesizing trial exclusion criteria with clinical judgement, we propose the START checklist (stable hemodynamics, tubular reserve, acid–base stability, risk factors, timing (24–72 h)) as provisional guidance to support bedside decision-making while large outcome studies, such as the empagliflozin after acute myocardial infarction (EMPACT-MI) trial and the extended empagliflozin to prevent worsening of left ventricular volumes and systolic function after myocardial infarction (EMPRESS-MI) trial read-outs, are awaited. Current evidence supports the hemodynamic and renal safety of commencing SGLT2i soon after PCI in hemodynamically stable STEMI patients with preserved tubular reserve. In the absence of ongoing trials, cautious adoption guided by the START framework can help clinicians capture potential cardio–renal benefits without compromising acute care.
Farhan et al. (Wed,) studied this question.