What are the benefits and risks of triple therapy (Oral Anticoagulant (OAC) + Dual Antiplatelet Therapy (DAPT)) compared to dual therapy (OAC + P2Y12 inhibitor) in patients with atrial fibrillation?

From the Guidelines

Dual therapy (OAC + P2Y12 inhibitor) is generally preferred over triple therapy (OAC + DAPT) for most patients with atrial fibrillation who require anticoagulation and have undergone percutaneous coronary intervention (PCI) or have acute coronary syndrome. The main benefit of dual therapy is a significantly reduced bleeding risk (approximately 40-50% lower) compared to triple therapy while maintaining similar protection against ischemic events 1. Triple therapy, which adds aspirin (usually 75-100mg daily) to the OAC and P2Y12 inhibitor, may provide marginally better protection against stent thrombosis but at the cost of substantially increased bleeding complications, including major and fatal bleeding. Some key points to consider when deciding between dual and triple therapy include:

• The patient's thrombotic and bleeding risks, with regular reassessment of the need for antiplatelet therapy alongside anticoagulation 1
• The use of a direct oral anticoagulant (DOAC) such as apixaban, rivaroxaban, or dabigatran plus clopidogrel 75mg daily as the preferred dual therapy regimen 1
• The potential to minimize the duration of triple therapy to a period of 4 to 6 weeks, as this is the period of greatest risk of stent thrombosis, especially in patients with ACS 1
• The consideration of double therapy with a P2Y12 inhibitor (clopidogrel) and dabigatran 150 mg twice daily as a reasonable alternative to triple therapy in patients with AF at increased risk of stroke 1. When triple therapy is necessary (typically in patients at very high thrombotic risk and lower bleeding risk), it should be kept as short as possible, usually 1-7 days after PCI, before de-escalating to dual therapy. For most patients, dual therapy should be continued for 6-12 months after PCI, followed by OAC monotherapy for long-term management. The decision between these strategies should be individualized based on each patient's thrombotic and bleeding risks, with regular reassessment of the need for antiplatelet therapy alongside anticoagulation 1.

From the Research

Benefits and Risks of Triple Therapy vs Dual Therapy

• The benefits and risks of triple therapy (Oral Anticoagulant (OAC) + Dual Antiplatelet Therapy (DAPT)) compared to dual therapy (OAC + P2Y12 inhibitor) in patients with atrial fibrillation have been studied in several randomized controlled trials 2.
• Triple therapy has been shown to increase the risk of major bleeding, with an annual rate exceeding 10% 2, 3.
• Dual therapy with OAC and a P2Y12 inhibitor has been found to reduce the rate of major and clinically relevant non-major bleeding compared to triple therapy, while being non-inferior for prevention of ischemic events 2.

Comparison of Triple Therapy and Dual Therapy

• Five major randomized clinical trials have compared double antithrombotic therapy with OAC and a P2Y12 inhibitor versus triple therapy in patients with atrial fibrillation who underwent PCI or had an ACS event 2.
• The trials showed that double antithrombotic therapy reduced the rate of major and clinically relevant non-major bleeding compared with triple therapy and was non-inferior for prevention of ischemic events, including cardiovascular death, myocardial infarction, or stroke 2.
• Consensus guidelines recommend that patients with atrial fibrillation who undergo PCI or have an ACS event should be treated with triple antithrombotic therapy (OAC + P2Y12 inhibitor + aspirin) for 7 days or less, followed by double antithrombotic therapy (OAC + P2Y12 inhibitor) for 6 to 12 months 2.

Clinical Decision-Making

• Clinical decision-making should be guided by the assessment of ischemic and bleeding risks 4.
• The use of clinical risk scores, such as the CHA2DS2-VASc score for stroke risk and the CRUSADE score for bleeding risk, can help guide treatment decisions 4.
• A moderate correlation between stroke risk and bleeding risk has been identified, highlighting the need for careful consideration of these risks in treatment decisions 4.

Evidence and Guidelines

• The evidence on the proper combination and duration of anticoagulant and antiplatelet agents in patients with indications for both therapies is limited 3, 5.
• Practice guidelines recommend oral anticoagulant therapy for most patients with atrial fibrillation and consideration of "triple therapy" (oral anticoagulant and aspirin and clopidogrel) when there is a concomitant acute coronary syndrome or stent placement, though acknowledging the risks of major bleeding 6.