When should Dual Antiplatelet Therapy (DAPT) be initiated and what is the preferred choice between ticagrelor and clopidogrel (Plavix) for a patient presenting with unstable angina?

Dual Antiplatelet Therapy for Unstable Angina: Initiation and Agent Selection

For patients presenting with unstable angina, initiate dual antiplatelet therapy (DAPT) immediately upon presentation with aspirin plus ticagrelor (180 mg loading dose, then 90 mg twice daily) as the preferred first-line regimen, continuing for 12 months unless excessive bleeding risk exists. 1, 2, 3

When to Initiate DAPT

Start DAPT immediately at presentation when unstable angina is diagnosed, before any invasive procedures are performed. 1, 2 This applies to all unstable angina patients regardless of whether they will be managed:

• Medically (conservative strategy) 1, 3
• With percutaneous coronary intervention (PCI) 1, 2
• With coronary artery bypass grafting (CABG) 3

The antiplatelet effect is needed within hours to reduce ischemic events, which is why loading doses are critical. 2, 4

Ticagrelor vs. Clopidogrel: The Definitive Choice

First-Line: Ticagrelor

Ticagrelor is superior to clopidogrel and should be the default P2Y12 inhibitor for unstable angina. 1, 2, 3 The evidence supporting this recommendation includes:

• Ticagrelor reduces cardiovascular death by 21% compared to clopidogrel (4.0% vs 5.1%, p=0.001) in acute coronary syndrome patients 2
• Ticagrelor reduces myocardial infarction by 16% (5.8% vs 6.9%, p=0.005) 2
• Ticagrelor reduces all-cause mortality by 24% (4.5% vs 5.9%, p<0.001) 2

Dosing: 180 mg loading dose immediately, then 90 mg twice daily 1, 2, 3

Critical aspirin dosing requirement: When using ticagrelor, maintain aspirin at 75-100 mg daily (or 81 mg in the US)—higher doses reduce ticagrelor's efficacy 2, 3, 5

When to Use Clopidogrel Instead

Clopidogrel (300-600 mg loading dose, then 75 mg daily) should be selected in these specific circumstances: 1, 2, 3

1. Prior intracranial hemorrhage (absolute contraindication to ticagrelor) 1, 2, 5
2. Need for oral anticoagulation (triple therapy)—clopidogrel has significantly lower bleeding risk than ticagrelor in this setting 1, 2
3. High bleeding risk with inability to tolerate potent P2Y12 inhibition (PRECISE-DAPT score ≥25, CRUSADE score >50) 1, 2
4. Patient already on chronic oral anticoagulation for atrial fibrillation or other indication 1
5. Ticagrelor contraindications: active bleeding, severe hepatic impairment, or documented hypersensitivity 5

Prasugrel: A Third Option for Specific Scenarios

Prasugrel (60 mg loading dose, then 10 mg daily) can be used only at the time of PCI in P2Y12 inhibitor-naïve patients, but has critical contraindications: 1, 2, 3

Absolute contraindications to prasugrel:

• Prior stroke or TIA (Class III: Harm—increases cerebrovascular events) 1, 2, 3
• Age ≥75 years 2, 3
• Body weight <60 kg 2, 3

Prasugrel should never be used in medically managed unstable angina patients (those not undergoing PCI). 1, 3

Algorithmic Approach to P2Y12 Inhibitor Selection

Step 1: Screen for absolute contraindications

• Prior intracranial hemorrhage → Use clopidogrel 2, 5
• Prior ischemic stroke/TIA → Use ticagrelor (NOT prasugrel) 2, 3
• Need for oral anticoagulation → Use clopidogrel 1, 2

Step 2: Assess bleeding risk

• High bleeding risk (PRECISE-DAPT ≥25, CRUSADE >50) → Consider clopidogrel 1, 2
• Standard bleeding risk → Proceed to Step 3

Step 3: Determine management strategy

• Conservative/medical management → Ticagrelor (loading dose immediately) 1, 2, 3
• Early invasive strategy with PCI planned → Ticagrelor (can give before catheterization) OR Prasugrel (give at time of PCI if no contraindications) 1, 2
• Urgent CABG likely within 5-7 days → Consider delaying P2Y12 inhibitor until after catheterization to avoid surgical bleeding, but give ticagrelor immediately if patient is unstable 1

Duration of DAPT

Standard duration: 12 months for all unstable angina patients regardless of management strategy (medical, PCI, or CABG). 1, 2, 3

Shortened duration (6 months): Consider only in patients who develop high bleeding risk during treatment (major bleeding event, need for anticoagulation, major surgery planned). 1, 2, 3

Extended duration (>12 months): May be considered in patients who tolerate DAPT without bleeding complications and have high ischemic risk. 1, 3

Critical Bleeding Risk Mitigation Strategies

Every unstable angina patient on DAPT should receive: 1, 2, 3

1. Proton pump inhibitor (PPI) to reduce gastrointestinal bleeding—this is mandatory, not optional 1, 2, 3
2. Low-dose aspirin (75-100 mg daily, never exceed 100 mg with ticagrelor) 1, 2, 3
3. Radial artery access if cardiac catheterization is performed (reduces access site bleeding) 1, 2

Common Pitfalls to Avoid

1. Never use prasugrel in patients with prior stroke/TIA—this is a Class III: Harm recommendation with increased risk of fatal intracranial bleeding 1, 2, 3

2. Never use high-dose aspirin (>100 mg) with ticagrelor—this reduces ticagrelor's efficacy 2, 3

3. Never discontinue DAPT in the first month after stent placement, even for elective surgery—the risk of stent thrombosis is catastrophic 1, 2, 3

4. Never fail to prescribe a PPI with DAPT—this simple intervention significantly reduces GI bleeding without compromising antiplatelet efficacy 1, 2, 3

5. Never use clopidogrel as first-line when ticagrelor is available and not contraindicated—this represents suboptimal care given ticagrelor's mortality benefit 2, 3

6. Never give prasugrel to medically managed patients (those not undergoing PCI)—it is not indicated and increases bleeding risk 1, 3

7. Never delay DAPT initiation in unstable patients waiting for catheterization—the ischemic risk outweighs bleeding concerns, even if CABG is ultimately needed 1, 6

Special Consideration: Switching from Clopidogrel to Ticagrelor

If a patient presents on chronic clopidogrel therapy, switch to ticagrelor immediately by giving the 180 mg loading dose without waiting for clopidogrel washout. 2, 3, 5 This applies even if the patient received clopidogrel loading dose within the previous 24 hours. 2

Genetic Testing Consideration

Clopidogrel requires CYP2C19 metabolism to become active. Patients who are CYP2C19 poor metabolizers (homozygous for loss-of-function alleles) have reduced antiplatelet effect and higher event rates. 4 This is another reason to prefer ticagrelor, which does not require CYP2C19 metabolism. 2 If clopidogrel must be used, consider genetic testing, though switching to ticagrelor is simpler and more effective than testing. 4