What are the recommendations for Dual Antiplatelet Therapy (DAPT) with aspirin and clopidogrel?

Dual Antiplatelet Therapy (DAPT) with Aspirin and Clopidogrel: Recommendations

For acute coronary syndrome (ACS) patients, DAPT with aspirin 81 mg daily and clopidogrel 75 mg daily should be administered for at least 12 months, with clopidogrel given as a 300 mg loading dose initially. 1

Acute Coronary Syndrome (ACS)

Initial Dosing and Duration

• In patients with non-ST-elevation ACS (NSTE-ACS) or ST-elevation myocardial infarction (STEMI), administer a 300 mg loading dose of clopidogrel followed by 75 mg daily, combined with aspirin 81 mg daily (range 75-100 mg) for at least 12 months. 1, 2
• The loading dose is critical when an antiplatelet effect is needed within hours; without it, establishment of antiplatelet effect is delayed by several days. 2
• Aspirin should be maintained at 81 mg daily (not higher doses) to minimize bleeding risk while maintaining efficacy. 1

Important Caveat on P2Y12 Inhibitor Selection

• While clopidogrel is effective, ticagrelor or prasugrel are preferred over clopidogrel in ACS patients when not contraindicated, as they provide superior reduction in cardiovascular death and myocardial infarction. 1, 3
• Clopidogrel remains appropriate for patients with prior intracranial bleeding, those requiring oral anticoagulation, or when newer agents are contraindicated. 1, 3

Stable Ischemic Heart Disease (SIHD) with Percutaneous Coronary Intervention (PCI)

Drug-Eluting Stents (DES)

• After DES implantation in SIHD patients, clopidogrel 75 mg daily should be given for at least 6 months. 1
• Aspirin 81 mg daily (range 75-100 mg) should be continued indefinitely. 1

Bare-Metal Stents (BMS)

• After BMS implantation, clopidogrel 75 mg daily should be given for a minimum of 1 month. 1

Extended DAPT Consideration

• In patients who have tolerated DAPT without bleeding complications and are not at high bleeding risk, continuation beyond the minimum duration (>1 month for BMS, >6 months for DES) may be reasonable. 1
• This decision requires absence of prior bleeding on DAPT, no coagulopathy, and no oral anticoagulant use. 1

Minor Ischemic Stroke or High-Risk TIA

Acute Management

• In patients with minor ischemic stroke (NIHSS ≤3) or high-risk TIA (ABCD2 ≥4), initiate DAPT with aspirin 81 mg daily and clopidogrel 75 mg daily as early as possible, ideally within 12-24 hours of symptom onset, after excluding intracranial hemorrhage. 1
• Administer loading doses: aspirin 160-325 mg and clopidogrel 300-600 mg at initiation. 1
• Continue DAPT for 21 days, then transition to single antiplatelet therapy (aspirin 81 mg daily or clopidogrel 75 mg daily). 1

Intracranial Atherosclerotic Stenosis

• In patients with moderate to high-grade intracranial atherosclerotic stenosis (50-99%), dual antiplatelet therapy is appropriate medical therapy; angioplasty and stenting is not recommended. 1

Critical Safety Measures to Minimize Bleeding

Aspirin Dosing

• Use low-dose aspirin (75-100 mg or 81 mg daily) rather than higher doses when combined with clopidogrel. 1

Proton Pump Inhibitor (PPI) Co-prescription

• A PPI should be prescribed in combination with DAPT, particularly in patients with history of gastrointestinal bleeding or increased bleeding risk. 1
• Avoid omeprazole and esomeprazole specifically, as they significantly reduce clopidogrel's antiplatelet activity through CYP2C19 inhibition; pantoprazole or rabeprazole are preferred alternatives. 1, 2

Radial Access for PCI

• Use radial over femoral access for coronary angiography and PCI when performed by an experienced radial operator. 1

High Bleeding Risk Scenarios

• In patients who develop high bleeding risk (e.g., requiring oral anticoagulation, major intracranial surgery planned) or significant overt bleeding after DES implantation, discontinuation of clopidogrel after 3 months may be reasonable. 1
• In ACS patients with high bleeding risk, consider shortening DAPT duration to 6 months if bleeding risk outweighs ischemic benefit. 1

Pharmacogenetic Considerations

• Clopidogrel effectiveness depends on CYP2C19 metabolism; patients who are CYP2C19 poor metabolizers (homozygous for nonfunctional alleles) form less active metabolite and have reduced antiplatelet effect. 2
• Consider using ticagrelor or prasugrel instead of clopidogrel in identified CYP2C19 poor metabolizers. 2
• Avoid concomitant use of strong CYP2C19 inhibitors (omeprazole, esomeprazole) with clopidogrel. 2

Triple Therapy (DAPT + Oral Anticoagulation)

• When triple therapy is required, keep duration as short as possible; clopidogrel is the P2Y12 inhibitor of choice (not ticagrelor or prasugrel). 1
• Use low-dose aspirin (≤100 mg daily) and consider target INR of 2.0-2.5 when warfarin is used. 1
• PPIs should be used in patients with history of gastrointestinal bleeding and are reasonable in those with increased bleeding risk. 1

Common Pitfalls to Avoid

• Do not discontinue DAPT within the first month after stent placement for elective non-cardiac surgery unless absolutely necessary. 1
• Do not use clopidogrel without a loading dose in ACS when rapid antiplatelet effect is needed. 2
• Do not combine clopidogrel with omeprazole or esomeprazole; this combination significantly impairs clopidogrel's antiplatelet activity. 1, 2
• Do not use higher aspirin doses (>100 mg) when combined with clopidogrel, as this increases bleeding without improving efficacy. 1
• Do not forget PPI co-prescription in patients on DAPT, especially those with bleeding risk factors. 1