What are the recommended antiplatelet and anticoagulant therapies, including doses, for patients with Acute Coronary Syndrome (ACS)?

Antiplatelet and Anticoagulant Selection in Acute Coronary Syndrome

All ACS patients should receive dual antiplatelet therapy (DAPT) with aspirin plus a P2Y12 inhibitor for 12 months, combined with parenteral anticoagulation during the acute phase. 1

Immediate Antiplatelet Therapy

Aspirin (Universal Foundation)

• Loading dose: Non-enteric-coated, chewable aspirin 162-325 mg (or 75-250 mg IV if unable to take oral) given immediately upon presentation 1
• Maintenance dose: 75-100 mg daily continued indefinitely 1
• When using ticagrelor specifically, limit aspirin maintenance to 81 mg daily 1

P2Y12 Inhibitor Selection Algorithm

For patients undergoing PCI (invasive strategy):

First-line choices (in order of preference):

1. Ticagrelor 1, 2

   • Loading dose: 180 mg orally
   • Maintenance: 90 mg twice daily
   • Preferred over clopidogrel for reducing major adverse cardiovascular events 1, 2
   • Can be given regardless of prior P2Y12 inhibitor use 1

2. Prasugrel 1, 3

   • Loading dose: 60 mg orally (given only after coronary anatomy is known in NSTE-ACS) 3
   • Maintenance: 10 mg daily (reduce to 5 mg daily if weight <60 kg) 3
   • Contraindications (Class III: Harm): Prior stroke or TIA at any time 3, 4
   • Generally avoid in patients ≥75 years old due to increased fatal and intracranial bleeding risk 3
   • Recent evidence from ISAR-REACT-5 showed prasugrel reduced death, MI, or stroke compared to ticagrelor (6.9% vs 9.3%, p=0.006) with similar bleeding rates 5

3. Clopidogrel (only when prasugrel or ticagrelor unavailable or contraindicated) 1

   • Loading dose: 600 mg orally
   • Maintenance: 75 mg daily
   • Less potent with slower onset (2 hours vs 30 minutes for newer agents) and higher on-treatment platelet reactivity (30-40% vs 3%) 5

Critical timing consideration: For NSTE-ACS patients, prasugrel loading should be delayed until coronary anatomy is established to avoid excessive bleeding if urgent CABG is needed 3. Ticagrelor or clopidogrel can be given earlier 1.

Glycoprotein IIb/IIIa Inhibitors (Bailout/High-Risk Situations)

Eptifibatide or tirofiban may be considered for: 1, 6, 7

• Bail-out during PCI if no-reflow or thrombotic complications occur 1
• P2Y12-inhibitor naïve patients with intermediate/high-risk features (e.g., positive troponin) undergoing PCI 1
• Massive coronary thrombus 7

Eptifibatide dosing: 6

• Loading: 180 mcg/kg IV bolus
• Maintenance: 2 mcg/kg/min infusion (reduce to 1 mcg/kg/min if creatinine clearance <50 mL/min)
• Second bolus: 180 mcg/kg at 10 minutes for PCI patients

Do NOT use: Upstream GP IIb/IIIa inhibitors before coronary anatomy is known (Class III recommendation) 1

Parenteral Anticoagulation (Acute Phase)

All ACS patients require anticoagulation in addition to antiplatelet therapy. 1 Select based on bleeding risk, renal function, and invasive strategy timing:

First-Line Options:

1. Enoxaparin (preferred for medical management or delayed invasive strategy) 1

   • Dose: 1 mg/kg subcutaneous every 12 hours
   • Renal adjustment: 1 mg/kg once daily if creatinine clearance <30 mL/min 1
   • Continue for duration of hospitalization or until PCI performed 1
   • Optional 30 mg IV loading dose in selected patients 1

2. Fondaparinux (lowest bleeding risk) 1

   • Dose: 2.5 mg subcutaneous once daily
   • Continue for duration of hospitalization or until PCI 1
   • Critical caveat: Must add UFH bolus (85 IU/kg, or 60 IU/kg if using GP IIb/IIIa inhibitor) during PCI to prevent catheter thrombosis 1

3. Bivalirudin (for early invasive strategy) 1

   • Loading: 0.10 mg/kg IV bolus
   • Maintenance: 0.25 mg/kg/hour until diagnostic angiography or PCI 1
   • Alternative dosing during PCI: 0.75 mg/kg bolus followed by 1.75 mg/kg/hour for up to 4 hours post-procedure 1

4. Unfractionated Heparin (UFH) 1

   • Dose: Weight-based IV bolus followed by infusion (target aPTT 1.5-2.5 times control)
   • Continue for 48 hours or until PCI performed 1
   • Most flexible option, especially if CABG likely 1

Never crossover between UFH and LMWH (Class III recommendation) 1

Duration of DAPT

Standard duration: 12 months for all ACS patients without excessive bleeding risk 1, 2

Shortened duration (3-6 months): Reasonable in high bleeding risk patients (e.g., PRECISE-DAPT score ≥25) 1, 4, 5

Extended duration (>12 months): May be considered in low bleeding risk patients, though optimal duration beyond 12 months is not well established 1, 5

Critical warning: The first month post-ACS carries the highest thrombotic risk; DAPT interruption during this period dramatically increases stent thrombosis and death risk 4, 8, 2

Bleeding Risk Mitigation

• Proton pump inhibitor: Class I recommendation for all patients on DAPT to reduce GI bleeding 4, 2
• Radial access: Preferred over femoral for PCI to reduce bleeding complications 2
• Low-dose aspirin: Use 75-100 mg (or 81 mg with ticagrelor) rather than higher doses 1, 4

Special Populations

Patients requiring long-term anticoagulation:

• Discontinue aspirin at 1-4 weeks post-PCI 2
• Continue P2Y12 inhibitor (preferably clopidogrel due to lower bleeding risk) with anticoagulant 2

Post-operative patients with ACS:

• Resume DAPT as soon as hemostasis is secure 4, 8
• For high bleeding risk, prefer clopidogrel over ticagrelor/prasugrel 4

Patients with prior stroke/TIA:

• Absolutely avoid prasugrel (6.5% stroke rate vs 1.2% with clopidogrel) 3, 5
• Use ticagrelor or clopidogrel instead 1, 2