Dapagliflozin Benefits in Patients with History of Myocardial Infarction
In patients with a history of myocardial infarction (MI), dapagliflozin provides significant cardiovascular and metabolic benefits, particularly in those with type 2 diabetes, reducing major adverse cardiovascular events (MACE) by 16% and cardiovascular death or heart failure hospitalization by 19%, with the greatest absolute risk reductions occurring within 2 years of the acute event. 1
Evidence in Patients with Prior MI and Type 2 Diabetes
The DECLARE-TIMI 58 trial demonstrated that dapagliflozin reduces MACE by 16% (HR 0.84,95% CI 0.72-0.99) in patients with type 2 diabetes and previous MI, translating to an absolute risk reduction of 2.6% (15.2% vs 17.8%). 1 This benefit was specific to patients with prior MI—no MACE reduction was observed in patients without previous MI (HR 1.00,95% CI 0.88-1.13), including those with established atherosclerotic cardiovascular disease but no MI history. 1
The timing of dapagliflozin initiation appears critical: patients treated within 2 years of their most recent acute MI derived greater MACE benefit (P for interaction trend=0.007), suggesting early initiation maximizes cardiovascular protection. 1
For the composite of cardiovascular death or heart failure hospitalization, dapagliflozin reduced relative risk by 19% in patients with prior MI (HR 0.81,95% CI 0.65-1.00), with an absolute risk reduction of 1.9% (8.6% vs 10.5%). 1 This benefit was consistent regardless of MI history, though absolute risk reductions were greater in the prior MI population. 1
Evidence in Acute MI Without Diabetes or Heart Failure
The DAPA-MI trial, the most recent and highest-quality study specifically addressing this question, enrolled 4017 patients presenting with acute MI and impaired left ventricular systolic function but without prior diabetes or chronic heart failure. 2 After approximately 1 year of treatment with dapagliflozin 10 mg daily:
- The hierarchical composite outcome (death, heart failure hospitalization, nonfatal MI, atrial fibrillation/flutter, type 2 diabetes, NYHA class, and ≥5% body weight decrease) showed significant benefit with dapagliflozin (win ratio 1.34,95% CI 1.20-1.50, P<0.001). 2
- However, the composite of cardiovascular death or heart failure hospitalization showed no significant difference: 2.5% with dapagliflozin vs 2.6% with placebo (HR 0.95% CI 0.64-1.40). 2
- The win ratio benefit was primarily driven by cardiometabolic outcomes rather than hard cardiovascular endpoints. 2
This contrasts with the EMPACT-MI trial of empagliflozin in a similar population, which also failed to show significant reduction in the primary endpoint of heart failure hospitalization or all-cause death (HR 0.90,95% CI 0.76-1.06, P=0.21), though hospitalization for heart failure alone was reduced (HR 0.77,95% CI 0.60-0.98). 3
Evidence in Heart Failure Patients with Prior MI
A pooled analysis of DAPA-HF and DELIVER trials including 11,007 patients with symptomatic heart failure across the entire ejection fraction spectrum found that 34% had prior MI. 4 These patients faced higher risk of cardiovascular death or worsening heart failure even after adjusting for covariates (HR 1.12,95% CI 1.02-1.24). 4
Dapagliflozin reduced the primary outcome consistently in patients with prior MI (HR 0.83,95% CI 0.72-0.96) and without prior MI (HR 0.76,95% CI 0.68-0.85), with no significant interaction (P=0.36). 4 Benefits extended across the entire left ventricular ejection fraction spectrum, including those with preserved ejection fraction. 4
Clinical Algorithm for Dapagliflozin Use Post-MI
For Patients with Type 2 Diabetes and Prior MI:
- Initiate dapagliflozin 10 mg daily if eGFR ≥25 mL/min/1.73 m² for cardiovascular and renal protection, regardless of glycemic control needs. 5, 6
- Prioritize initiation within 2 years of the most recent MI to maximize MACE reduction. 1
- Continue dapagliflozin even if eGFR falls below 45 mL/min/1.73 m², as cardiovascular and renal benefits persist despite reduced glycemic efficacy. 7
For Patients with Acute MI Without Diabetes or Heart Failure:
- Based on DAPA-MI results, dapagliflozin provides cardiometabolic benefits but does not significantly reduce cardiovascular death or heart failure hospitalization in this population. 2
- The 2025 ACC/AHA ACS guidelines note that dapagliflozin was not beneficial in patients without diabetes or heart failure after MI. 5
- Consider deferring SGLT2 inhibitor initiation unless the patient develops heart failure or diabetes during follow-up. 5
For Patients with Heart Failure and Prior MI:
- Initiate dapagliflozin 10 mg daily regardless of ejection fraction (reduced, mildly reduced, or preserved) if eGFR ≥25 mL/min/1.73 m². 4, 8
- Benefits occur within weeks of initiation and are independent of diabetes status, age, sex, or background medical therapy. 8
Dosing and Safety Considerations
The fixed dose is 10 mg orally once daily for all cardiovascular and renal indications—no titration is required or recommended. 5, 7 This differs from other heart failure medications that require up-titration. 8
Withhold dapagliflozin at least 3 days before major surgery or procedures requiring prolonged fasting to prevent postoperative ketoacidosis. 5, 7 During acute illness with reduced oral intake, fever, vomiting, or diarrhea, patients should temporarily discontinue dapagliflozin and contact their healthcare provider. 7
Monitor for genital mycotic infections (approximately 6% incidence), urinary tract infections, and volume depletion, particularly in patients on concurrent diuretics or with baseline eGFR 30-60 mL/min/1.73 m². 5, 7 An initial transient eGFR decline of 3-5 mL/min/1.73 m² within 1-4 weeks is expected and does not indicate kidney injury—do not discontinue therapy for this reason. 7
Key Pitfalls to Avoid
Do not discontinue dapagliflozin solely because eGFR falls below 45 mL/min/1.73 m²—cardiovascular and renal protective benefits persist even when glycemic efficacy is lost. 7 The drug can be continued until dialysis is required if eGFR falls below 25 mL/min/1.73 m² in patients already on treatment. 7
Do not assume class effect across all SGLT2 inhibitors for post-MI populations without diabetes or heart failure—both DAPA-MI and EMPACT-MI failed to show significant benefit for hard cardiovascular endpoints in this specific population. 2, 3 The robust benefits are established primarily in patients with diabetes, heart failure, or chronic kidney disease. 1, 4
Do not delay initiation in eligible patients with prior MI and diabetes—the greatest MACE benefit occurs when treatment begins within 2 years of the acute event. 1