What are the indications for triple therapy with antiplatelet and anticoagulant medications?

Triple Therapy (Antiplatelet with Anticoagulant) Indications

Triple therapy with anticoagulant and dual antiplatelet agents should be limited to the shortest duration possible (typically 1 month) and only used in patients at high ischemic risk following percutaneous coronary intervention (PCI), particularly those with acute coronary syndrome (ACS). 1

Primary Indications for Triple Therapy

• Patients with atrial fibrillation (AF) who undergo PCI, especially those with high thrombotic risk features 1
• Recent ACS with stent placement in patients who have a concomitant indication for oral anticoagulation (such as AF, mechanical heart valve, or venous thromboembolism) 1
• High ischemic risk due to anatomical/procedural characteristics that outweigh bleeding risk (complex PCI, bifurcation lesions, multiple stents) 1

Duration of Triple Therapy

• Standard duration: 1 month of triple therapy (OAC + aspirin + clopidogrel) irrespective of stent type 1
• Extended duration (up to 6 months) may be considered only in patients with very high ischemic risk that outweighs bleeding risk 1
• After triple therapy period: transition to dual therapy (OAC + single antiplatelet) for up to 12 months, followed by OAC alone 1

Medication Selection for Triple Therapy

• Anticoagulant: Non-vitamin K antagonist oral anticoagulants (NOACs) are preferred over vitamin K antagonists (VKAs) 1

  • Use the lowest approved dose effective for stroke prevention 1
  • For rivaroxaban: 15mg once daily (instead of 20mg) when combined with antiplatelet drugs 1
  • For VKAs: target INR in the lower part of therapeutic range (2.0-2.5) 1

• P2Y12 inhibitor: Clopidogrel is the only recommended P2Y12 inhibitor for triple therapy 1

  • Ticagrelor and prasugrel are NOT recommended as part of triple therapy due to higher bleeding risk 1

• Aspirin: Low-dose aspirin (75-100mg daily) 1

Risk Mitigation Strategies

• Proton pump inhibitors should be routinely used to reduce gastrointestinal bleeding risk 1
• Radial access is preferred for coronary angiography to minimize access site bleeding 2
• HAS-BLED score can help predict bleeding risk in patients on triple therapy 3
• In patients with high bleeding risk: consider avoiding triple therapy altogether and use dual therapy (OAC + clopidogrel) instead 1, 4

Important Considerations

• Bleeding risk is significantly increased with triple therapy compared to dual therapy (threefold increase in major bleeding at one year) 4, 3
• Recent evidence suggests dual therapy (OAC + P2Y12 inhibitor) may be non-inferior to triple therapy for preventing thrombotic events while causing significantly less bleeding 1, 4
• Current guidelines recommend against routine use of triple therapy for most patients, with dual therapy (OAC + P2Y12 inhibitor) being the default strategy 1

Common Pitfalls to Avoid

• Prolonging triple therapy beyond necessary duration - keep to the shortest effective period 1
• Using prasugrel or ticagrelor as part of triple therapy - these potent P2Y12 inhibitors significantly increase bleeding risk 1
• Failing to reassess thrombotic and bleeding risks periodically during treatment 1
• Not using gastroprotection with proton pump inhibitors during triple therapy 1