What is the recommended antiplatelet therapy for patients with Acute Coronary Syndrome (ACS)?

Antiplatelet Therapy in Acute Coronary Syndrome

All patients with ACS must receive dual antiplatelet therapy (DAPT) consisting of aspirin plus a P2Y12 inhibitor for 12 months, regardless of whether they undergo PCI, receive medical management alone, or proceed to CABG. 1, 2

Optimal DAPT Regimen

First-Line P2Y12 Inhibitor Selection

Ticagrelor (180 mg loading dose, then 90 mg twice daily) plus aspirin 75-100 mg daily is the preferred first-line regimen for all ACS patients. 1, 2 This applies to both STEMI and NSTEMI presentations, regardless of initial management strategy. 1

Prasugrel (60 mg loading dose, then 10 mg daily) plus aspirin is the alternative first-line option for P2Y12 inhibitor-naïve patients with ACS undergoing PCI, unless contraindications exist. 1, 2 Prasugrel should be administered only after coronary anatomy is known in NSTEMI patients. 3

Clopidogrel (300-600 mg loading dose, then 75 mg daily) is reserved only for patients who cannot receive ticagrelor or prasugrel due to contraindications or need for oral anticoagulation. 2, 4 Clopidogrel represents suboptimal therapy when more potent P2Y12 inhibitors are available. 1

Critical Contraindications to Prasugrel

• Never prescribe prasugrel to patients with prior stroke or TIA - this is an absolute contraindication due to increased cerebrovascular bleeding risk (6.5% vs 1.2% with clopidogrel). 3, 5
• Prasugrel is generally not recommended for patients ≥75 years old due to increased fatal and intracranial bleeding risk, except in high-risk situations (diabetes or prior MI). 3
• Consider dose reduction to 5 mg daily for patients <60 kg due to increased bleeding risk. 3

Standard Duration of DAPT

The default DAPT duration is 12 months for all ACS patients who are not at high bleeding risk, regardless of ACS type (STEMI vs NSTEMI), stent type, or completeness of revascularization. 1, 2, 6 This recommendation applies even to patients managed medically without PCI. 1

For ACS patients with high bleeding risk, shortened DAPT duration of 6 months may be reasonable. 1, 2 High bleeding risk is traditionally defined as ≥4% annual risk of serious bleeding or ≥1% risk of intracranial hemorrhage. 5

Anticoagulation in Addition to DAPT

All ACS patients require anticoagulation in addition to antiplatelet therapy, irrespective of initial treatment strategy. 7 Treatment options include:

• Enoxaparin: 1 mg/kg SC every 12 hours (reduce to once daily if CrCl <30 mL/min) 7
• Bivalirudin: 0.10 mg/kg loading dose followed by 0.25 mg/kg/hour (only for early invasive strategy with provisional GP IIb/IIIa inhibitor use) 7
• Fondaparinux: 2.5 mg SC daily (requires additional anticoagulant with anti-IIa activity if PCI performed due to catheter thrombosis risk) 7
• UFH: 60 IU/kg loading dose (max 4000 IU) with 12 IU/kg/hour infusion (max 1000 IU/h) adjusted to aPTT 7

Mandatory Bleeding Risk Mitigation

Proton Pump Inhibitor Co-Prescription

Prescribe a PPI to all patients on DAPT - this is a Class I recommendation. 1, 8 PPIs are superior to H2 receptor antagonists in preventing upper GI bleeding (odds ratio 0.04 vs 0.43). 8 This simple intervention significantly reduces gastrointestinal bleeding without compromising antiplatelet efficacy. 1, 2

Additional Bleeding Risk Reduction Strategies

• Use radial artery access over femoral access for PCI when performed by an experienced radial operator. 1, 2
• Maintain aspirin dose at 75-100 mg daily (not higher doses) when combined with a P2Y12 inhibitor. 1, 2
• Avoid concomitant use of NSAIDs which increase bleeding risk. 3, 4

Special Clinical Scenarios

Switching from Clopidogrel to Ticagrelor

For ACS patients previously on clopidogrel, switch to ticagrelor early after hospital admission with a 180 mg loading dose, regardless of timing and loading dose of clopidogrel. 2 Discontinue clopidogrel when ticagrelor is commenced. 2

ACS Patients Undergoing CABG

Resume P2Y12 inhibitor therapy after CABG to complete 12 months of DAPT. 1 When possible, discontinue prasugrel at least 7 days prior to CABG. 3 Continue aspirin perioperatively if bleeding risk allows. 1, 2

Patients Requiring Oral Anticoagulation

For patients requiring long-term anticoagulation, discontinue aspirin 1-4 weeks after PCI and continue P2Y12 inhibitor, preferably clopidogrel rather than ticagrelor, due to significantly lower bleeding risk with triple therapy. 2

Critical Pitfalls to Avoid

• Never discontinue DAPT prematurely, especially within the first month after stent placement - this dramatically increases risk of stent thrombosis, MI, and death. 1, 2
• Never fail to prescribe a PPI with DAPT - this simple intervention significantly reduces GI bleeding. 1, 8
• Never use clopidogrel as first-line therapy when ticagrelor or prasugrel are available and not contraindicated - this represents suboptimal care. 1, 2
• Never administer prasugrel to patients with prior stroke or TIA - this is absolutely contraindicated. 3, 5
• Never use prasugrel in medically managed ACS patients not undergoing PCI - prasugrel is indicated only for patients managed with PCI. 2, 3

Monitoring for Thrombocytopenia

Immediately discontinue GP IIb/IIIa inhibitors and/or heparin if thrombocytopenia <100,000/mL or >50% relative drop from baseline occurs. 7 Platelet transfusion is recommended for major active bleeding or severe thrombocytopenia (<10,000/mL). 7