What is the recommended antiplatelet regimen for patients post Percutaneous Coronary Intervention (PCI) stenting, comparing aspirin (acetylsalicylic acid) alone versus aspirin + clopidogrel?

Dual Antiplatelet Therapy is Mandatory After PCI Stenting

Aspirin alone is inadequate and potentially dangerous after PCI stenting—dual antiplatelet therapy (DAPT) with aspirin plus a P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor) is the required standard of care. 1

Core Recommendation: DAPT Duration Based on Clinical Presentation

For Acute Coronary Syndrome (ACS) Patients

• DAPT must be continued for at least 12 months regardless of stent type (bare-metal or drug-eluting) 1
• Preferred P2Y12 inhibitors in ACS:
  • Ticagrelor 90 mg twice daily (180 mg loading dose) is recommended as first-line over clopidogrel 1
  • Prasugrel 10 mg daily (60 mg loading dose) is recommended for P2Y12-naïve patients with NSTE-ACS or STEMI undergoing immediate PCI, unless high bleeding risk or contraindications exist 1, 2
  • Clopidogrel 75 mg daily (600 mg loading dose) is reserved for patients who cannot receive ticagrelor or prasugrel, including those with prior intracranial bleeding 1

For Stable Coronary Artery Disease (Non-ACS) Patients

• Drug-eluting stents (DES): DAPT for at least 6-12 months if not at high bleeding risk 1
• Bare-metal stents (BMS): DAPT for minimum 1 month, ideally up to 12 months (minimum 2 weeks if high bleeding risk) 1
• The 2024 ESC guidelines establish 6 months as the default DAPT duration for stable patients with DES 1

Aspirin Dosing Strategy

• Low-dose aspirin 75-100 mg daily is superior to higher doses and should be used during DAPT to minimize bleeding complications 1
• Aspirin must be continued indefinitely after the P2Y12 inhibitor is stopped 1
• Higher loading doses (325 mg) are acceptable immediately before PCI in aspirin-naïve patients, but maintenance should be 75-100 mg 1

After DAPT Completion: Long-Term Monotherapy

• Aspirin monotherapy indefinitely is the traditional approach after completing the recommended DAPT duration 1
• However, emerging evidence suggests clopidogrel monotherapy may be superior: A 2023 meta-analysis demonstrated that clopidogrel reduced MACE (RR 0.77), any stroke (RR 0.51), ischemic stroke (RR 0.55), and hemorrhagic stroke (RR 0.24) compared to aspirin, with no difference in mortality or major bleeding 3
• Clopidogrel 75 mg daily is recommended as a safe and effective alternative to aspirin monotherapy 4

Critical Timing Considerations

Early Period (First 30 Days)

• Highest risk for stent thrombosis occurs in the first month, particularly with BMS 4
• Both antiplatelet agents must be maintained unless life-threatening bleeding occurs 1
• If life-threatening bleeding necessitates stopping DAPT, transfer patient to a primary PCI facility immediately 1

Extended Period (1-12 Months)

• Drug-eluting stents carry higher late thrombosis risk than bare-metal stents throughout the first year 4, 5
• Continuation beyond 12 months may be considered in select high-risk patients (IIb recommendation), though this remains controversial 1

Special Populations and Modifications

High Bleeding Risk Patients

• PRECISE-DAPT score ≥25 indicates excessive bleeding risk and may warrant shorter DAPT duration 1
• Consider 1-3 months DAPT in patients with very high or high risk of life-threatening bleeding 1
• Never discontinue both agents simultaneously in the early post-stent period unless bleeding is life-threatening 1, 4

Patients Requiring Oral Anticoagulation

• After uncomplicated PCI, discontinue aspirin early (≤1 week) and continue dual therapy with oral anticoagulant plus clopidogrel 1, 4
• Triple therapy (aspirin + clopidogrel + anticoagulant) should be limited to ≤1 month unless ischemic risk clearly outweighs bleeding risk 1
• NOACs are preferred over warfarin when eligible 1, 4
• Ticagrelor and prasugrel are not recommended as part of triple antithrombotic therapy 1

Perioperative Management

• Elective surgery requiring P2Y12 inhibitor discontinuation should be delayed until at least 1 month post-stenting if aspirin can be maintained 1
• Non-urgent surgery should ideally be delayed 12 months after stent placement 4
• If both agents must be stopped, bridging with cangrelor, tirofiban, or eptifibatide may be considered, especially within 1 month of stenting 1

Mandatory Adjunctive Therapy

• Proton pump inhibitors (PPIs) are recommended in all patients on DAPT to reduce GI bleeding risk 1
• PPIs are particularly important in patients with prior GI bleeding, advanced age, concomitant warfarin/NSAID use, or H. pylori infection 1

What NOT to Do

• Do not use aspirin monotherapy in the first 12 months after ACS with stenting 1
• Do not use aspirin monotherapy in the first 1-6 months after stable CAD stenting (depending on stent type) 1
• Do not routinely perform platelet function testing to adjust therapy before or after elective stenting 1
• Do not use fondaparinux alone during PCI due to catheter thrombosis risk 1
• Do not discontinue DAPT without cardiology consultation, as patients must understand the catastrophic consequences of premature cessation 1

The Evidence Hierarchy

The strongest evidence comes from the 2024 ESC guidelines 1 and 2017 ESC focused update 1, which incorporate data from multiple large randomized trials. The 2011 ACC/AHA/SCAI guidelines 1 established the foundational 12-month DAPT recommendation for ACS, which remains unchanged. The TRITON-TIMI 38 trial 2 demonstrated prasugrel's superiority over clopidogrel in ACS but with increased bleeding. Recent meta-analyses 3 suggest clopidogrel may be preferable to aspirin for long-term monotherapy, representing an evolving area where practice may shift from traditional aspirin-based strategies.