What is the recommended treatment regimen for a patient with Acute Coronary Syndrome (ACS)?

Acute Coronary Syndrome Treatment Regimen

All patients with ACS should immediately receive dual antiplatelet therapy (DAPT) consisting of aspirin plus ticagrelor (180 mg loading dose, then 90 mg twice daily) for 12 months, combined with parenteral anticoagulation and high-intensity statin therapy, regardless of whether they undergo percutaneous coronary intervention (PCI), medical management, or coronary artery bypass grafting (CABG). 1, 2

Immediate Antiplatelet Therapy

First-Line P2Y12 Inhibitor Selection

• Ticagrelor is the preferred P2Y12 inhibitor for all ACS patients (STEMI, NSTEMI, unstable angina) irrespective of planned treatment strategy 1, 2, 3

  • Loading dose: 180 mg immediately upon diagnosis 1, 2, 3
  • Maintenance: 90 mg twice daily 1, 2, 3
  • Continue for 12 months unless excessive bleeding risk exists 1, 2, 3

• Prasugrel is the alternative first-line option for P2Y12 inhibitor-naïve patients undergoing PCI 1, 2, 3

  • Loading dose: 60 mg immediately before PCI 1, 2, 3
  • Maintenance: 10 mg daily (5 mg if age ≥75 years or weight <60 kg) 1
  • Contraindicated in patients with prior stroke or TIA due to increased cerebrovascular bleeding risk 1, 2, 3, 4

• Clopidogrel is reserved only for patients who cannot receive ticagrelor or prasugrel 1, 2, 3

  • Loading dose: 300-600 mg 1, 3
  • Maintenance: 75 mg daily 1, 3
  • Use when ticagrelor/prasugrel are contraindicated, unavailable, or patient requires oral anticoagulation 1, 2

Aspirin Administration

• Aspirin 75-100 mg daily should be given to all ACS patients immediately 1, 2, 3
• Higher loading doses (160-325 mg) may be given initially, but maintenance should be 75-100 mg to minimize bleeding risk when combined with P2Y12 inhibitors 1, 2, 3

Parenteral Anticoagulation

All ACS patients require parenteral anticoagulation in addition to antiplatelet therapy at the time of diagnosis and during revascularization procedures 1, 2

For Patients Undergoing PCI

• Unfractionated heparin (UFH) is recommended during PCI 1
  • Weight-adjusted IV bolus: 70-100 IU/kg (or 50-70 IU/kg if combined with GP IIb/IIIa inhibitor) 1
  • Target activated clotting time (ACT): 250-350 seconds (or 200-250 seconds with GP IIb/IIIa inhibitor) 1

For Medical Management or Delayed PCI

• Fondaparinux is recommended when medical treatment is planned or logistical constraints delay PCI 1
• A single bolus of UFH is recommended at the time of PCI if fondaparinux was used 1

Alternative Anticoagulation Options

• Enoxaparin, bivalirudin, or fondaparinux may be used based on ischemic and bleeding risk profiles 1, 2, 5, 6
• Do not crossover between UFH and low-molecular-weight heparin (LMWH) 1

Anti-Ischemic Medications in Acute Phase

• Sublingual or IV nitrates are recommended for patients with ongoing ischemic symptoms without contraindications 1
• IV nitrates are recommended for patients with uncontrolled hypertension or signs of heart failure 1
• Early initiation of beta-blocker therapy is recommended for patients with ongoing ischemic symptoms without contraindications 1
• Continue chronic beta-blocker therapy unless the patient has overt heart failure 1

High-Intensity Statin Therapy

• Initiate high-intensity statin therapy (regimens that reduce LDL cholesterol by ≥50%) as early as possible after admission in all ACS patients 1, 5
• This should be started in the absence of contraindications 1

Mandatory Bleeding Risk Mitigation Strategies

Every ACS patient on DAPT must receive the following bleeding risk reduction measures:

• Proton pump inhibitor (PPI) co-prescription for all patients on DAPT (Class I recommendation) 1, 2, 3, 5

  • PPIs are superior to H2 receptor antagonists in preventing upper GI bleeding 2

• Radial artery access over femoral access for PCI when performed by an experienced radial operator 1, 2, 3

• Maintain aspirin dose at 75-100 mg daily when combined with P2Y12 inhibitor 1, 2, 3

Duration of DAPT

• Standard duration is 12 months for all ACS patients regardless of stent type, ACS type, or completeness of revascularization 1, 2, 3

• Shortened duration (6 months) may be reasonable for patients with high bleeding risk 1, 2, 3

• Do not discontinue DAPT within the first month after stent placement, as this dramatically increases risk of stent thrombosis, MI, and death 2, 3

Timing of Invasive Strategy

An immediate invasive strategy (<2 hours) is recommended for patients with at least one very high-risk criterion: 1

• Hemodynamic instability or cardiogenic shock 1
• Recurrent or refractory chest pain despite medical treatment 1
• Life-threatening arrhythmias 1
• Mechanical complications 1

Special Clinical Scenarios

Patients Previously on Clopidogrel

• Switch to ticagrelor immediately after hospital admission with 180 mg loading dose, regardless of timing and loading dose of clopidogrel 2, 3
• Do not wait for clopidogrel washout 3

Patients Requiring Chronic Oral Anticoagulation

• After a short period of triple antithrombotic therapy (TAT) up to 1 week, transition to dual antithrombotic therapy (DAT) using a NOAC at recommended dose for stroke prevention plus a single antiplatelet agent (preferably clopidogrel) 1

• Periprocedural DAPT (aspirin and clopidogrel) up to 1 week is recommended 1

• Do not use ticagrelor or prasugrel as part of triple therapy 1

• Discontinue aspirin 1-4 weeks after PCI and continue P2Y12 inhibitor (preferably clopidogrel) with oral anticoagulation 1, 2

• Discontinue antiplatelet treatment after 12 months in patients treated with oral anticoagulation 1

Patients Undergoing CABG

• Resume P2Y12 inhibitor therapy after CABG to complete 12 months of DAPT 2
• Eptifibatide infusion should be discontinued prior to CABG surgery 7

GP IIb/IIIa Inhibitors

• Not recommended for routine pre-treatment in patients in whom coronary anatomy is not known and early invasive management is planned 1

• Not recommended in patients in whom coronary anatomy is not known 1

• May be used during PCI in high-risk patients, particularly those with large thrombus burden 7

Eptifibatide Dosing (if used)

• For ACS (medical management): 180 mcg/kg IV bolus followed by 2 mcg/kg/min infusion (1 mcg/kg/min if creatinine clearance <50 mL/min) 7
• For PCI: 180 mcg/kg IV bolus immediately before PCI, followed by 2 mcg/kg/min infusion and second 180 mcg/kg bolus 10 minutes after first bolus 7

Secondary Prevention (Long-Term Management)

ACE Inhibitors

• ACE inhibitors are recommended for patients with systolic LV dysfunction or heart failure, hypertension, or diabetes 1
• Use agents and doses of proven efficacy 1
• ARBs are indicated for patients intolerant of ACE inhibitors 1

Beta-Blockers

• Beta-blockers are recommended in patients with reduced systolic LV function (LVEF ≤40%) 1
• Use agents and doses of proven efficacy 1

Lifestyle Modifications

• Mandatory smoking cessation 1, 5
• Dietary modification and physical rehabilitation 1

Critical Pitfalls to Avoid

• Never use clopidogrel as first-line therapy when ticagrelor or prasugrel are available and not contraindicated 2, 3

• Never discontinue DAPT prematurely, especially within the first month after stent placement 2, 3

• Never fail to prescribe a PPI with DAPT 2, 3

• Never administer prasugrel to patients with prior stroke or TIA 1, 2, 3, 4

• Never crossover between UFH and LMWH 1

• Never use ticagrelor or prasugrel as part of triple antithrombotic therapy in patients requiring oral anticoagulation 1

Monitoring for Thrombocytopenia

• Immediately discontinue GP IIb/IIIa inhibitors and/or heparin if thrombocytopenia <100,000/mL or >50% relative drop from baseline occurs 1, 2

• Platelet transfusion is recommended for major active bleeding or severe thrombocytopenia (<10,000/mL) in patients treated with GP IIb/IIIa inhibitors 1

• Use non-heparin anticoagulant in case of documented or suspected heparin-induced thrombocytopenia (HIT) 1