What is the treatment for Non-ST-Elevation Myocardial Infarction (NSTEMI)?

Treatment of Non-ST-Elevation Myocardial Infarction (NSTEMI)

All NSTEMI patients should receive immediate dual antiplatelet therapy (aspirin plus clopidogrel or another P2Y12 inhibitor) combined with anticoagulation, followed by risk stratification to determine whether an early invasive strategy (coronary angiography within 12-48 hours) or an initial conservative strategy is most appropriate. 1

Immediate Medical Therapy (All Patients)

Antiplatelet Therapy

• Aspirin should be initiated immediately in all patients unless contraindicated 1
• Clopidogrel should be added to aspirin as dual antiplatelet therapy 1, 2
  • Loading dose: 300 mg orally for patients needing antiplatelet effect within hours 2
  • Maintenance: 75 mg daily 2
  • Critical caveat: Clopidogrel effectiveness is reduced in CYP2C19 poor metabolizers; consider alternative P2Y12 inhibitors (prasugrel or ticagrelor) in these patients 2
  • Avoid concomitant omeprazole or esomeprazole as they significantly reduce clopidogrel's antiplatelet activity 2

Anticoagulation

• Enoxaparin (LMWH) is preferable to unfractionated heparin unless renal failure is present or CABG is planned within 24 hours 1
• Anticoagulation should be added to antiplatelet therapy in all patients 1

Anti-Ischemic Therapy

• Beta-blockers should be administered unless contraindicated 1
• Nitrates for symptom relief and ongoing ischemia 1
• Morphine for pain relief if needed 3
• Oxygen if hypoxemic 3

Risk Stratification for Invasive Strategy Selection

High-Risk Features Favoring Early Invasive Strategy

The following criteria identify patients who benefit most from routine early invasive management 1:

• Elevated troponin (troponin T >0.01 ng/mL or troponin I >0.1 ng/mL) 1
• ST-segment deviation on ECG 1
• TIMI risk score ≥3 1
• Recurrent ischemia despite medical therapy 1
• Hemodynamic instability 1
• Sustained ventricular arrhythmias 1

Treatment Strategy Selection

Early Invasive Strategy (Preferred for High-Risk Patients)

For patients with high-risk features, an early invasive strategy with coronary angiography performed within 12-48 hours followed by revascularization if appropriate provides superior outcomes compared to conservative management. 1

Evidence Supporting Early Invasive Approach:

• The TACTICS-TIMI 18 trial demonstrated that in high-risk patients treated with aspirin, heparin, and GP IIb/IIIa inhibitor (tirofiban), early invasive strategy reduced death/MI/rehospitalization at 6 months from 19.4% to 15.9% (p=0.025) 1
• Death or MI specifically was reduced from 9.5% to 7.3% (p<0.05) 1
• The FRISC-II trial showed 1-year mortality of 2.2% with invasive strategy versus 3.9% with conservative strategy (p=0.016) 1, 4
• At 5 years, invasive strategy maintained benefit with HR 0.81 (p=0.009) for death or nonfatal MI 1, 4

Timing of Angiography:

• Within 12-24 hours for very high-risk patients (refractory angina, hemodynamic instability, arrhythmias) 5
• Within 24-48 hours for other high-risk patients 1, 5
• The TIMACS trial demonstrated that early angiography (within 24 hours) reduced ischemic complications particularly in patients with GRACE score >140 1

GP IIb/IIIa Inhibitor Consideration:

• When using early invasive strategy, upstream GP IIb/IIIa inhibitor (tirofiban or eptifibatide) administration eliminates the excess early MI risk seen with invasive procedures 1
• This was a key component of the TACTICS-TIMI 18 success, where tirofiban was given for average 22 hours before angiography 1

Initial Conservative (Selective Invasive) Strategy

For initially stabilized patients without high-risk features, an initial conservative strategy with angiography reserved for recurrent ischemia or strongly positive stress testing is a reasonable alternative. 1

When Conservative Strategy Is Appropriate:

• Patients without elevated troponin, ST-segment changes, or high TIMI risk score 1
• Clinically stable patients without recurrent ischemia 1
• Patients at very high surgical risk 1

Important Caveat:

The ICTUS trial showed no difference between routine invasive and selective invasive strategies at 1 year, but this trial had limitations including high crossover rates (47% of conservative arm underwent revascularization) and lower-risk population 1

Revascularization Method Selection

Percutaneous Coronary Intervention (PCI)

• Drug-eluting stents are preferred over balloon angioplasty alone when PCI is performed 3
• Modern trials showing benefit of invasive strategy predominantly used coronary stenting 1

Coronary Artery Bypass Grafting (CABG)

• Reserved for patients with anatomy unsuitable for PCI or with left main/multivessel disease where CABG provides superior outcomes 1
• Stop clopidogrel 5-7 days before planned CABG due to bleeding risk 2

Secondary Prevention (All Patients)

Mandatory Long-Term Therapies:

• Dual antiplatelet therapy continuation (aspirin plus P2Y12 inhibitor) 1
• High-intensity statin therapy for aggressive lipid lowering 1
• Beta-blockers unless contraindicated 1
• ACE inhibitors or ARBs particularly if LVEF is reduced 6

Critical Clinical Pitfalls to Avoid

1. Do not delay invasive strategy in truly high-risk patients thinking a "cooling off" period is beneficial—the ISAR-COOL trial showed that delayed invasive strategy (86 hours) had worse outcomes than very early strategy (2.4 hours), with events occurring during the waiting period 1

2. Do not use troponin elevation alone as the sole criterion for invasive strategy selection with increasingly sensitive assays; consider the degree of elevation plus other clinical risk factors 1

3. Do not combine clopidogrel with omeprazole or esomeprazole—this significantly reduces antiplatelet efficacy 2

4. Do not assume all patients benefit equally from early invasive strategy—the benefit is primarily in medium- to high-risk patients, not low-risk patients 1, 4

5. Recognize that in-hospital mortality is actually higher with early invasive strategy (1.8% vs 1.1%), but this is more than offset by reduced post-discharge mortality (3.8% vs 4.9%) 1