Management of Myocardial Infarction with Non-Obstructive Coronary Artery Disease (MINOCA)
The management of MINOCA requires a systematic diagnostic approach to identify the underlying mechanism, followed by mechanism-specific therapy, with RAAS inhibitors and statins forming the cornerstone of secondary prevention, while intensive dual antiplatelet therapy should be avoided as it may cause harm without benefit.
Diagnostic Workup
MINOCA is defined as myocardial infarction with positive cardiac biomarkers, clinical evidence of infarction, and absence of significant coronary stenosis (≥50%) on angiography 1, 2. The condition accounts for approximately 6-8% of patients with spontaneous MI referred for coronary angiography and disproportionately affects women 1.
A systematic diagnostic approach is essential to identify the underlying mechanism:
Routine echocardiography during hospital stay is recommended to assess LV and RV function, detect early post-MI mechanical complications, and exclude LV thrombus 3.
The combination of invasive coronary angiography, multivessel intracoronary imaging, provocative testing for coronary spasm, and cardiac magnetic resonance imaging provides the greatest diagnostic yield 1.
Cardiac MRI should be performed during the first month after discharge to exclude non-ischemic causes of troponin elevation and identify the underlying mechanism 4.
The dominant mechanisms include atherosclerotic plaque disruption with thrombosis, coronary artery spasm, coronary embolism, spontaneous coronary artery dissection (SCAD), and coronary microvascular dysfunction 1, 2, 5.
Acute Phase Management
Initial Stabilization
Admit to a monitored unit with continuous rhythm monitoring for at least 24 hours 6.
Administer supplemental oxygen if arterial oxygen saturation is <90% 6, 7.
Consider nitroglycerin for ongoing ischemic symptoms unless contraindicated 6.
Antiplatelet Therapy
Administer aspirin 162-325 mg immediately upon presentation, then continue with low-dose aspirin (75-100 mg) indefinitely 6, 3.
Avoid intensified dual antiplatelet therapy (DAPT) regimens in MINOCA patients. A critical study demonstrated that double-dose clopidogrel (600 mg day 1,150 mg days 2-7, then 75 mg/day) resulted in significantly higher rates of adverse events compared to standard-dose clopidogrel in MINOCA patients (2.1% vs 0.6% primary outcome, HR 3.57,95% CI 1.31-9.76), whereas no such harm was seen in obstructive CAD 8.
If DAPT is used, standard-dose clopidogrel (300 mg loading, then 75 mg daily) is preferred over more potent P2Y12 inhibitors due to lower bleeding risk and lack of proven benefit 8.
Anticoagulation
Administer anticoagulation with unfractionated heparin, enoxaparin, fondaparinux, or bivalirudin during the acute phase 6.
Continue anticoagulation for at least 48 hours or until discharge if managed medically 6.
Secondary Prevention Therapy
RAAS Inhibitors (Highest Priority)
RAAS inhibitors are the only medication class with demonstrated mortality benefit in MINOCA patients and should be initiated in all patients unless contraindicated.
ACE inhibitors should be started within the first 24 hours in patients with heart failure, LV systolic dysfunction (LVEF <40%), diabetes, or anterior infarct 3.
In a prospective study, RAAS inhibitors were the only medication associated with reduced all-cause mortality and MACE in MINOCA patients on multivariable analysis 4.
ARBs (preferably valsartan) are an alternative for ACE inhibitor-intolerant patients 3.
Initiate lisinopril 2.5-5 mg daily, titrating to target doses of 10-40 mg daily as tolerated 9.
Statin Therapy
High-intensity statin therapy should be started as early as possible and maintained long-term 3.
Target LDL-C <1.8 mmol/L (70 mg/dL) or a reduction of at least 50% if baseline LDL-C is between 1.8-3.5 mmol/L (70-135 mg/dL) 3.
Patients treated with statins had significantly longer survival in MINOCA cohorts 4.
Atorvastatin 20-80 mg daily is recommended 10.
Beta-Blocker Therapy
Oral beta-blockers are indicated in patients with heart failure and/or LVEF <40% unless contraindicated 3.
However, beta-blocker therapy showed no effect on mortality and MACE in MINOCA-specific studies 4.
Avoid intravenous beta-blockers in patients with hypotension, acute heart failure, AV block, or severe bradycardia 3.
If used, initiate metoprolol tartrate 25-50 mg every 6 hours initially, then transition to 100 mg twice daily for maintenance 11.
Mineralocorticoid Receptor Antagonists
- MRAs are recommended in patients with ejection fraction <40% and heart failure or diabetes, who are already receiving an ACE inhibitor and beta-blocker, provided there is no renal failure or hyperkalemia 3.
Risk Stratification and Long-Term Management
Measure left ventricular ejection fraction during hospitalization 6.
If LVEF ≤0.40, consider diagnostic angiography if not already performed 6.
If LVEF >0.40, consider stress testing for risk stratification 6.
Participation in a cardiac rehabilitation program is recommended 3.
Identify smokers and provide repeated advice on stopping, with offers for nicotine replacement therapies, varenicline, and bupropion 3.
Gastrointestinal Protection
- A PPI in combination with antiplatelet therapy is recommended in patients at high risk of gastrointestinal bleeding 3, 7.
Critical Pitfalls to Avoid
Do not use intensified DAPT regimens (high-dose clopidogrel, prasugrel, or ticagrelor) routinely in MINOCA patients, as evidence suggests possible harm without benefit 8.
Do not assume MINOCA is benign—patients have a 12.5% all-cause mortality and 17% MACE rate at approximately 19 months follow-up 4.
Do not apply obstructive CAD treatment protocols uniformly to MINOCA patients—current guidelines are based largely on obstructive CAD data, and optimal medications remain uncertain 1.
Avoid NSAIDs (except aspirin) during hospitalization due to increased risks of mortality, reinfarction, hypertension, heart failure, and myocardial rupture 6.
Do not administer immediate-release dihydropyridine calcium channel blockers without adequate beta-blockade 6.