What is the initial treatment for Acute Coronary Syndrome (ACS) Non-ST-Elevation Myocardial Infarction (NSTEMI) in the Intensive Care Unit (ICU), including when to start heparin infusion?

Initial Treatment of NSTEMI in the ICU

Start antiplatelet therapy immediately with aspirin 162-325 mg (chewable, non-enteric coated) plus a P2Y12 inhibitor loading dose, and initiate anticoagulation with unfractionated heparin (60 IU/kg bolus, maximum 4000 IU, followed by 12 IU/kg/hour infusion, maximum 1000 IU/hour) as soon as the diagnosis is established. 1, 2

Immediate Antiplatelet Therapy (Within Minutes of Presentation)

Aspirin Administration

• Give aspirin 162-325 mg immediately in chewable, non-enteric coated form for rapid onset 1, 3
• If oral administration impossible, use IV aspirin 250-500 mg 1, 3
• Continue aspirin 75-81 mg daily indefinitely 1

P2Y12 Inhibitor Selection (Choose Based on Strategy)

For Early Invasive Strategy (planned catheterization within 24-72 hours):

• Ticagrelor 180 mg loading dose (preferred, can give upstream before angiography) 1, 3
• OR Clopidogrel 600 mg loading dose (alternative if ticagrelor contraindicated) 1, 3
• Prasugrel should NOT be given upstream—wait until coronary anatomy is known and PCI is planned 1, 3

For Conservative/Ischemia-Guided Strategy:

• Clopidogrel 300 mg loading dose followed by 75 mg daily 1, 3
• Continue for minimum 1 month, ideally up to 12 months 1

Anticoagulation: When to Start Heparin Infusion

Timing of Heparin Initiation

Start heparin infusion immediately upon diagnosis of NSTEMI, as soon as possible after hospital presentation 1, 2

Unfractionated Heparin (UFH) Dosing Protocol

• Initial bolus: 60 IU/kg (maximum 4000 IU) 1, 2
• Infusion: 12 IU/kg/hour (maximum 1000 IU/hour) 1, 2
• Target aPTT: 1.5-2.0 times control (approximately 50-70 seconds) 2
• Check first aPTT at 3 hours, then adjust per hospital protocol 1, 2
• Continue for 48 hours or until PCI is performed 1, 2

Alternative Anticoagulation Options (If UFH Not Chosen)

Enoxaparin (preferred over UFH for conservative strategy):

• 1 mg/kg SC every 12 hours 1
• Optional 30 mg IV loading dose 1
• Reduce to 1 mg/kg SC once daily if CrCl <30 mL/min 1
• Continue for duration of hospitalization or until PCI 1

Fondaparinux:

• 2.5 mg SC daily 1
• Continue for duration of hospitalization or until PCI 1
• CRITICAL: Must add UFH or bivalirudin during PCI due to catheter thrombosis risk 1

Bivalirudin (for early invasive strategy only):

• 0.10 mg/kg loading dose followed by 0.25 mg/kg/hour infusion 1
• Continue until diagnostic angiography or PCI 1
• Use with provisional (not routine) GP IIb/IIIa inhibitor 1

Risk Stratification for Treatment Intensity

High-Risk Features Requiring Urgent/Immediate Invasive Strategy (Within 2-24 Hours)

• Refractory angina despite medical therapy 1
• Hemodynamic instability or cardiogenic shock 1
• Life-threatening arrhythmias 1
• Recurrent ischemia with ST-segment changes 1
• Heart failure symptoms 1
• Elevated troponin with dynamic ECG changes 1

Early Invasive Strategy (Within 24-72 Hours)

• Elevated cardiac biomarkers (troponin) 1
• New ST-segment depression 1
• GRACE risk score indicating high risk 1
• Diabetes mellitus 1
• Reduced left ventricular function (EF <40%) 1

GP IIb/IIIa Inhibitor Use

When to Add GP IIb/IIIa Inhibitors

For Early Invasive Strategy:

• Can add upstream (before catheterization) if high-risk features present and significant delay to catheterization expected 1
• Eptifibatide or tirofiban preferred for upstream use (NOT abciximab) 1
• Reasonable to omit upstream if clopidogrel 300-600 mg given ≥6 hours before catheterization AND bivalirudin chosen as anticoagulant 1

For Conservative Strategy:

• May add eptifibatide or tirofiban if recurrent ischemia despite aspirin, clopidogrel, and anticoagulation 1
• Abciximab should NEVER be given if PCI not planned 1

Critical Pitfalls to Avoid

Anticoagulation Errors

• Never switch between anticoagulants during same admission—increases bleeding risk significantly 2
• Never give UFH if patient already received enoxaparin—causes excessive bleeding 2
• Never use fondaparinux alone during PCI—must add UFH or bivalirudin bolus to prevent catheter thrombosis 1
• Never exceed UFH bolus of 70 IU/kg or infusion of 15 IU/kg/hour—associated with major bleeding 2

Antiplatelet Errors

• Never give prasugrel before knowing coronary anatomy—contraindicated if prior stroke/TIA, and dosing depends on anatomy 1, 3
• Never exceed aspirin 100 mg daily maintenance dose when using ticagrelor—increases bleeding without added benefit 1
• Never use enteric-coated aspirin for loading dose—delayed absorption negates immediate antiplatelet effect 1, 3

Monitoring Failures

• Never continue UFH beyond 48 hours without ongoing indication—no proven benefit and increases bleeding risk 2
• Never fail to check aPTT at 3 hours after starting UFH—essential for dose adjustment 2
• Never forget to adjust enoxaparin dose for renal dysfunction—accumulation causes severe bleeding 1, 2

Adjunctive Medical Therapy in ICU

Mandatory Therapies

• High-intensity statin (atorvastatin 80 mg or rosuvastatin 40 mg) started immediately 1
• Beta-blocker (oral, not IV) within 24 hours if no contraindications 1
• ACE inhibitor within 24 hours if heart failure, reduced EF, anterior MI, or diabetes 1
• Nitroglycerin (sublingual or IV) for ongoing chest pain 1, 4

Bleeding Risk Reduction

• Proton pump inhibitor for all patients on dual antiplatelet therapy, especially if history of GI bleeding 1, 3
• Avoid NSAIDs completely—increase risk of death, reinfarction, and cardiac rupture 1

Duration of Anticoagulation

• UFH: Continue for 48 hours or until PCI performed 1, 2
• Enoxaparin: Continue for duration of hospitalization, up to 8 days 1
• Fondaparinux: Continue for duration of hospitalization, up to 8 days 1
• Bivalirudin: Discontinue after PCI or continue at 0.25 mg/kg/hour for up to 72 hours at physician discretion 1