For a patient with a non‑ST‑elevation myocardial infarction and angiographically non‑obstructive coronary arteries (MINOCA), what dual antiplatelet therapy regimen is recommended?

DAPT for NSTEMI with Non-Obstructive Coronary Arteries (MINOCA)

For patients with NSTEMI and angiographically non-obstructive coronary arteries (MINOCA), dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor may be considered based on the most probable underlying mechanism, though evidence is limited and the benefit remains uncertain. 1

Initial Diagnostic Approach

Before committing to long-term DAPT, you must establish whether this is true MINOCA or an alternative diagnosis:

• Perform cardiac magnetic resonance imaging (CMR) in all MINOCA patients without an obvious underlying cause to differentiate true myocardial infarction from Takotsubo syndrome, myocarditis, or other non-ischemic conditions. 1
• Consider intracoronary imaging with IVUS or OCT when thrombus, plaque rupture/erosion, or spontaneous coronary artery dissection (SCAD) are suspected, as these may be missed on standard angiography. 1
• Exclude pulmonary embolism with D-dimer testing, BNP, and/or CT pulmonary angiography as appropriate, since this can mimic MINOCA. 1

DAPT Recommendation Algorithm

The decision to use DAPT hinges on the final diagnosis after complete workup:

If CMR/imaging reveals a specific non-atherosclerotic cause:

• Manage according to disease-specific guidelines (e.g., Takotsubo syndrome, myocarditis, SCAD). 1
• DAPT is generally not indicated for Takotsubo syndrome or myocarditis, as these are now excluded from the MINOCA definition. 1

If the final diagnosis is true MINOCA of unknown cause (after negative provocative tests and CMR):

• Consider DAPT (aspirin + P2Y12 inhibitor) based on pathophysiological reasoning, targeting the most probable causes: vasospastic angina, coronary plaque disruption, or thromboembolism. 1
• The benefit of DAPT in this scenario is uncertain, as evidence is scarce. 1
• Patients with a final diagnosis of MINOCA of unknown cause may be treated according to secondary prevention guidelines for atherosclerotic disease (Class IIb, Level C recommendation). 1

If diffuse non-obstructive atherosclerosis is present (<50% stenosis):

• Treat as atherosclerotic disease with full secondary prevention, including DAPT. 2
• These patients have a prognosis comparable to or worse than those with single-vessel obstructive disease, particularly if diabetic. 2

Specific DAPT Regimen When Indicated

When you decide DAPT is appropriate based on the above algorithm:

• Aspirin 75-100 mg daily indefinitely. 3, 4

• P2Y12 inhibitor selection:

  • Ticagrelor 90 mg twice daily (after 180 mg loading dose) is preferred over clopidogrel for superior cardiovascular outcomes. 3, 4
  • Clopidogrel 75 mg daily (after 300-600 mg loading dose) if ticagrelor is contraindicated or not tolerated. 3, 4
  • Prasugrel is NOT recommended in MINOCA patients, as it should only be used after coronary anatomy is defined and PCI is planned. 3, 5

• Duration: 12 months is the standard recommendation for ACS patients, though this is extrapolated from obstructive CAD data. 3, 4

Bleeding Risk Mitigation

• Prescribe a proton pump inhibitor (PPI) with DAPT to reduce gastrointestinal bleeding risk (Class I recommendation). 3, 4
• Maintain aspirin at 75-100 mg daily rather than higher doses to minimize bleeding without sacrificing efficacy. 3, 4

Critical Pitfalls to Avoid

• Do not reflexively prescribe DAPT without completing the diagnostic workup (CMR, provocative testing if indicated), as many MINOCA patients have non-atherosclerotic causes that do not benefit from antiplatelet therapy. 1
• Do not assume MINOCA is benign—these patients have higher mortality than age-matched controls and require systematic evaluation. 1, 2, 6
• Do not overlook diffuse atherosclerosis (<50% stenosis)—these patients have worse outcomes than those with truly normal coronaries and warrant aggressive secondary prevention. 2
• Do not use prasugrel in MINOCA patients, as it is only indicated when PCI is performed. 3, 5

When DAPT May NOT Be Appropriate

• If CMR reveals Takotsubo syndrome or myocarditis, DAPT is not indicated—these are excluded from the MINOCA definition. 1
• If the patient has high bleeding risk and no clear atherosclerotic mechanism, the uncertain benefit of DAPT may not justify the bleeding risk. 1
• If provocative testing confirms pure vasospastic angina, calcium channel blockers and nitrates are the primary therapy, with DAPT playing a secondary role. 1

The Evidence Gap

The 2020 ESC guidelines explicitly state that "evidence is scarce" for DAPT in true MINOCA of unknown cause. 1 The recommendation to consider DAPT is based on pathophysiological reasoning rather than randomized trial data, as most DAPT trials excluded patients without obstructive CAD. 1, 3 This underscores the importance of completing the diagnostic algorithm to identify patients most likely to benefit from antiplatelet therapy.