What is the recommended dual antiplatelet therapy regimen for a patient with ischemic heart disease?

Dual Antiplatelet Therapy for Ischemic Heart Disease

For acute coronary syndrome (ACS), ticagrelor (180 mg loading dose, 90 mg twice daily) plus aspirin (75-100 mg daily) is the first-line dual antiplatelet therapy (DAPT) regimen for 12 months, regardless of whether percutaneous coronary intervention (PCI) is performed. 1, 2

P2Y12 Inhibitor Selection Algorithm

First-Line: Ticagrelor

• Ticagrelor is recommended for all ACS patients (STEMI, NSTEMI, unstable angina) on top of aspirin, regardless of initial treatment strategy 1, 2
• Use even in patients pre-treated with clopidogrel—discontinue clopidogrel immediately when starting ticagrelor 1, 2
• Dosing: 180 mg loading dose, then 90 mg twice daily 1, 2
• Aspirin dose: 75-100 mg daily (or 81 mg in US) 2

Second-Line: Prasugrel

• Prasugrel is recommended for P2Y12 inhibitor-naïve patients with ACS undergoing PCI unless contraindications exist 1, 2
• Dosing: 60 mg loading dose, then 10 mg once daily 1, 3
• Critical contraindications to screen for: 3
  • Prior stroke or TIA (absolute contraindication—increases stroke risk from 1.2% to 6.5%) 3, 4
  • Age ≥75 years (generally not recommended due to increased fatal/intracranial bleeding) 3
  • Body weight <60 kg (reduce maintenance dose to 5 mg daily) 3
• Do NOT use prasugrel in medically managed ACS patients (without PCI) 1

Third-Line: Clopidogrel

• Clopidogrel is reserved for patients who cannot receive ticagrelor or prasugrel 1, 2
• Specific indications: 1, 2
  • Prior intracranial bleeding
  • Indication for oral anticoagulation (triple therapy)
  • High bleeding risk with inability to tolerate potent P2Y12 inhibition
• Dosing for stable CAD with PCI: 600 mg loading dose, then 75 mg daily 1
• Dosing for STEMI with thrombolysis: 300 mg loading dose (if age <75), then 75 mg daily 1

Duration of DAPT

Standard Duration: 12 Months

• All ACS patients require 12 months of DAPT with a P2Y12 inhibitor plus aspirin, whether managed with PCI, medical therapy alone, or CABG 1, 2, 4
• All patients undergoing PCI with stent placement require 12 months of DAPT 2, 4

Shortened Duration: 3-6 Months

• Consider shortening DAPT to 6 months (or less) if excessive bleeding risk exists 1, 2
• High bleeding risk defined as: PRECISE-DAPT score ≥25, or 1-year serious bleeding risk ≥4%, or intracranial hemorrhage risk ≥1% 1, 4
• Risk factors include: age ≥65 years, body weight <60 kg, BMI <18.5, diabetes, prior bleeding, concomitant oral anticoagulants 4

Prolonged Duration: Beyond 12 Months

• May consider prolonged DAPT in patients with peripheral artery disease or complex PCI if bleeding risk is low 1
• After 12 months, transition to ticagrelor monotherapy (discontinue aspirin) is recommended ≥1 month after PCI in patients who tolerated DAPT without bleeding 2

Bleeding Risk Mitigation Strategies

All patients on DAPT must receive these protective measures: 1, 2

• Use radial (not femoral) arterial access for coronary angiography and PCI when performed by expert radial operator 1, 2
• Maintain aspirin dose at 75-100 mg daily (not higher doses) 1, 2
• Prescribe a proton pump inhibitor (PPI) in combination with DAPT to reduce gastrointestinal bleeding 1, 2

Timing of P2Y12 Inhibitor Loading Dose

For NSTE-ACS:

• Do NOT administer prasugrel until coronary anatomy is known 1, 3
• Ticagrelor or clopidogrel may be given upstream (before angiography) if invasive strategy is delayed >24 hours 2

For STEMI:

• If presenting within 12 hours of symptom onset: administer loading dose at time of diagnosis (though most receive at time of PCI) 3
• If presenting >12 hours after symptom onset: wait until coronary anatomy is established 3

Switching Between P2Y12 Inhibitors

When switching from clopidogrel to ticagrelor in ACS patients: 1, 2

• Give ticagrelor 180 mg loading dose immediately
• No washout period required
• Switch regardless of timing and loading dose of clopidogrel
• Discontinue clopidogrel when ticagrelor is commenced

Critical Pitfalls to Avoid

• Never use prasugrel in patients with prior stroke/TIA—this is an absolute contraindication with proven harm 1, 2, 3, 4
• Never discontinue DAPT within the first month after stent placement for elective surgery—dramatically increases thrombotic risk 1, 2
• Never omit PPI co-prescription with DAPT—this simple intervention significantly reduces gastrointestinal bleeding 1, 2
• Never use clopidogrel as first-line therapy when ticagrelor is available and not contraindicated—represents suboptimal care for ACS patients 2
• Never use prasugrel in medically managed ACS patients without PCI—not recommended 1
• Never perform routine platelet function testing to adjust antiplatelet therapy before or after elective stenting 1

Special Populations

Patients Requiring Oral Anticoagulation (Triple Therapy):

• Use clopidogrel (not ticagrelor) as the P2Y12 inhibitor due to significantly lower bleeding risk 2
• Discontinue aspirin 1-4 weeks after PCI and continue P2Y12 inhibitor plus anticoagulant 2

Patients Undergoing Surgery:

• Continue aspirin perioperatively if bleeding risk allows 1, 2
• Resume recommended antiplatelet therapy as soon as possible post-operatively 1, 2
• For prasugrel specifically: discontinue at least 7 days prior to surgery when possible 3