Management of NSTEMI Without Revascularization (Medical Management Only)
For NSTEMI patients managed medically without stent or CABG, initiate dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor (preferably ticagrelor or prasugrel over clopidogrel) for 12 months, combined with parenteral anticoagulation, beta-blockers, statins, ACE inhibitors, and anti-ischemic medications. 1
Immediate Antiplatelet Therapy
Dual antiplatelet therapy (DAPT) is the cornerstone of medical management:
Aspirin: Administer immediately at 150-300 mg loading dose, then 75-100 mg daily indefinitely 1
P2Y12 Inhibitor - First Choice: Ticagrelor 180 mg loading dose, then 90 mg twice daily for 12 months, regardless of conservative management strategy 1. Ticagrelor is recommended over clopidogrel for all moderate-to-high risk NSTEMI patients with elevated troponins 1
P2Y12 Inhibitor - Alternative: Prasugrel 60 mg loading dose, then 10 mg daily (reduce to 5 mg daily if age ≥75 years or body weight <60 kg) 1. However, prasugrel is typically reserved for patients undergoing PCI rather than medical management alone
P2Y12 Inhibitor - Third Choice: Clopidogrel 300-600 mg loading dose, then 75 mg daily, only when ticagrelor or prasugrel are unavailable, not tolerated, or contraindicated 1, 2. The FDA label confirms clopidogrel reduces MI and stroke in NSTEMI patients managed medically 2
Critical caveat: Avoid routine pre-treatment with P2Y12 inhibitors if coronary anatomy is unknown and invasive management might still be planned, as this increases bleeding risk if CABG becomes necessary 1
Anticoagulation Therapy
Parenteral anticoagulation is mandatory in addition to antiplatelet therapy:
Preferred option for medical management: Fondaparinux 2.5 mg subcutaneously once daily, which has the best efficacy-safety profile for conservative management 1
Alternative: Low molecular weight heparin (LMWH) such as enoxaparin, dosed according to weight and renal function, is at least as effective as unfractionated heparin with easier administration 1, 3
Unfractionated heparin (UFH): Weight-adjusted IV bolus followed by continuous infusion (aPTT target 1.5-2.5 times control) if LMWH or fondaparinux unavailable 1
Duration: Continue anticoagulation throughout the acute phase (typically 2-8 days) until clinical stabilization 1
Important: Do not crossover between UFH and LMWH due to increased bleeding risk 1
Anti-Ischemic Medications
Beta-blockers and nitrates for symptom control and prognostic benefit:
Beta-blockers: Initiate early in patients with ongoing ischemic symptoms without contraindications (heart failure, hypotension, bradycardia, or heart block) 1. Continue chronic beta-blocker therapy unless overt heart failure develops 1
Nitrates: Sublingual or IV nitrates for ongoing chest pain, uncontrolled hypertension, or signs of heart failure 1. Avoid in right ventricular infarction, hypotension, or recent phosphodiesterase-5 inhibitor use
Morphine: For pain relief if nitrates insufficient, though use cautiously as it may reduce effectiveness of oral P2Y12 inhibitors 4
Secondary Prevention and Long-Term Therapy
Aggressive risk factor modification is essential for reducing mortality:
High-intensity statin: Initiate immediately regardless of baseline cholesterol (e.g., atorvastatin 80 mg or rosuvastatin 40 mg daily) to reduce recurrent events 1, 4
ACE inhibitor (or ARB): Start within 24 hours in all patients, particularly those with anterior MI, heart failure, LVEF <40%, diabetes, or hypertension 4, 5
Continue DAPT: Aspirin plus P2Y12 inhibitor for 12 months unless excessive bleeding risk, then transition to aspirin monotherapy indefinitely 1
Beta-blocker: Continue long-term, especially if LV dysfunction or heart failure present 1
Special Populations Requiring Dose Adjustments
Renal impairment:
- Assess eGFR in all patients and adjust anticoagulant and antiplatelet doses accordingly 1
- Use low- or iso-osmolar contrast if angiography eventually performed 1
Elderly patients (≥75 years):
- Apply same diagnostic and therapeutic strategies but reduce prasugrel dose to 5 mg daily if used 1
- Adjust antithrombotic dosing based on renal function and bleeding risk 1
Diabetes mellitus:
- Screen all NSTEMI patients for diabetes and monitor glucose frequently 1
- Avoid hypoglycemia which worsens outcomes 1
Patients Requiring Oral Anticoagulation
For NSTEMI patients with atrial fibrillation (CHA₂DS₂-VASc ≥2 in men, ≥3 in women):
After acute phase (up to 1 week): Transition from triple therapy (aspirin + clopidogrel + OAC) to dual therapy with oral anticoagulant plus single antiplatelet agent (preferably clopidogrel) 1
Avoid ticagrelor or prasugrel as part of triple antithrombotic therapy due to excessive bleeding risk 1
Discontinue antiplatelet therapy after 12 months, continuing OAC monotherapy for stroke prevention 1
Monitoring and Follow-Up
Risk stratification determines intensity of monitoring:
Patients with GRACE score >140, ongoing ischemia, hemodynamic instability, or life-threatening arrhythmias require intensive monitoring and reconsideration of invasive strategy 1
Low-risk patients (GRACE <109) can be managed conservatively with selective invasive strategy only if ischemia testing demonstrates significant reversible ischemia 1
Common Pitfalls to Avoid
Do not use GP IIb/IIIa inhibitors in medically managed patients without PCI, as bleeding risk outweighs benefit 1
Do not use clopidogrel as first-line P2Y12 inhibitor when ticagrelor is available, as ticagrelor provides superior outcomes in NSTEMI 1
Do not omit anticoagulation even with DAPT, as combined antithrombotic therapy is essential 1, 3
Do not forget proton pump inhibitor in patients at high GI bleeding risk (age >65, prior GI bleeding, anticoagulation use) 4
Recognize CYP2C19 poor metabolizers (2% of Whites, 4% of Blacks, 14% of Asians) have reduced clopidogrel effectiveness; consider alternative P2Y12 inhibitor 2