What is the most important change in the 2025 Acute Coronary Syndrome (ACS) guidelines that Emergency Department (ED) physicians need to know?

Major Change in 2025 ACS Guidelines: Antiplatelet Therapy in Patients Requiring Anticoagulation

The most important change in the 2025 ACS guidelines that ED physicians need to know is the recommendation to discontinue aspirin after 1-4 weeks of triple antithrombotic therapy in patients with ACS who require oral anticoagulant therapy, continuing only with a P2Y12 inhibitor (preferably clopidogrel) and an oral anticoagulant to reduce bleeding risk. 1

Rationale for This Change

This recommendation represents a significant shift in management strategy for a challenging patient population - those with ACS who also require oral anticoagulation for conditions like atrial fibrillation, venous thromboembolism, or prosthetic heart valves.

• Several randomized controlled trials have demonstrated that discontinuing aspirin 1-4 weeks after PCI reduces bleeding risk in patients requiring both DAPT and oral anticoagulation 1
• Meta-analyses show no significant difference in mortality, stroke, or overall major adverse cardiovascular events when aspirin is discontinued in patients on oral anticoagulants 1
• While there may be a marginal increase in MI and stent thrombosis risk, the overall benefit-to-risk ratio favors this approach 1

Implementation Algorithm

1. Initial Management (Day 0-7): Start triple therapy with:

   • Aspirin
   • P2Y12 inhibitor (preferably clopidogrel)
   • Oral anticoagulant (DOAC preferred over vitamin K antagonist)

2. Weeks 1-4: Discontinue aspirin after 1-4 weeks

   • Continue P2Y12 inhibitor (clopidogrel)
   • Continue oral anticoagulant

3. After Week 4 through 12 months: Maintain dual therapy

   • P2Y12 inhibitor (clopidogrel)
   • Oral anticoagulant

Important Considerations

• For patients at high risk of stent thrombosis, consider maintaining aspirin for up to 30 days after PCI 1
• 80% of stent thrombosis events occur within the first 30 days after PCI 1
• P2Y12 inhibitor therapy should be continued for at least 12 months after PCI following aspirin discontinuation 1
• In patients with multiple bleeding risk factors, P2Y12 inhibitor may be discontinued earlier 1

Bleeding Risk Assessment

The 2025 guidelines provide specific criteria to identify patients at high bleeding risk, including:

Major Criteria:

• Age ≥75 years
• Severe/end-stage CKD (eGFR <30 mL/min)
• Hemoglobin <11 g/dL
• Prior spontaneous ICH
• Active malignancy within past 12 months 1

Minor Criteria:

• Moderate CKD (eGFR 30-59 mL/min)
• Moderate/severe thrombocytopenia
• Recent major surgery
• Prior ischemic stroke 1

The presence of at least 1 major or 2 minor criteria identifies patients at increased bleeding risk who would particularly benefit from this new approach.

Practical Implications for ED Physicians

1. Recognize that triple therapy (aspirin + P2Y12 inhibitor + anticoagulant) significantly increases bleeding risk
2. Initiate triple therapy in the ED for ACS patients requiring anticoagulation
3. Ensure clear documentation and communication with cardiology and primary care about the plan to discontinue aspirin after 1-4 weeks
4. Educate patients about the importance of adherence to the remaining dual therapy (P2Y12 inhibitor + anticoagulant) after aspirin discontinuation
5. Consider bleeding risk factors when determining the optimal duration of triple therapy before aspirin discontinuation

This evidence-based approach optimizes the balance between preventing thrombotic events while minimizing potentially life-threatening bleeding complications in this high-risk patient population.