What is the recommended antithrombotic management for a patient presenting with acute coronary syndrome who is already on a direct oral anticoagulant (DOAC), including antiplatelet therapy, procedural anticoagulation for percutaneous coronary intervention, and timing of DOAC re‑initiation?

Antithrombotic Management for ACS in Patients Already on DOAC

For a patient on a DOAC who presents with acute coronary syndrome requiring PCI, continue the DOAC and add aspirin plus clopidogrel (not prasugrel or ticagrelor) during hospitalization, then discontinue aspirin within 1 week of discharge and continue dual therapy with DOAC plus clopidogrel for 12 months. 1

Periprocedural Anticoagulation Strategy

During PCI

• Administer additional parenteral anticoagulation (unfractionated heparin or bivalirudin) during the procedure regardless of DOAC timing or last dose 1
• The DOAC does not provide adequate procedural anticoagulation alone and must be supplemented 1
• Do not attempt to reverse the DOAC unless life-threatening bleeding occurs 1

Immediate Post-PCI Period (Hospitalization)

• Continue the same DOAC the patient was taking pre-procedure 1
• Administer loading doses of aspirin (if not already on it) and clopidogrel 600 mg 1
• Give low-dose aspirin (81 mg daily) plus clopidogrel 75 mg daily during hospitalization only 1
• Avoid prasugrel or ticagrelor as they dramatically increase bleeding risk when combined with anticoagulation 1

Post-Discharge Antiplatelet Strategy

First 1-4 Weeks After PCI

Discontinue aspirin within 1 week (up to 4 weeks maximum) after discharge and continue DOAC plus clopidogrel 1

This "triple therapy" window should be minimized because:

• Aspirin adds substantial bleeding risk without additional ischemic benefit when combined with DOAC and clopidogrel 1
• Multiple randomized trials demonstrate that early aspirin cessation (1-4 weeks) reduces bleeding without increasing mortality, stroke, or major adverse cardiovascular events 1
• Only extend triple therapy beyond 1 week in patients with extremely high ischemic risk (complex left main PCI, multivessel disease with suboptimal result, prior stent thrombosis) AND low bleeding risk 1

Months 1-12 After ACS

Continue dual therapy with DOAC plus clopidogrel 75 mg daily for 12 months 1

• This applies specifically to ACS presentations (STEMI, NSTEMI, unstable angina) 1
• For stable coronary disease requiring PCI (not ACS), dual therapy duration is only 6 months 1

Beyond 12 Months

Discontinue clopidogrel and continue DOAC monotherapy lifelong 1

• The indication for anticoagulation (atrial fibrillation, venous thromboembolism, mechanical valve) persists indefinitely 1
• No antiplatelet therapy is needed after 12 months unless the patient has additional high-risk features 1

DOAC Selection and Dosing

Preferred Agent

Continue the same DOAC the patient was taking before ACS; if switching from warfarin, use a DOAC rather than continuing warfarin 1

DOACs are preferred over warfarin because they:

• Reduce major bleeding, fatal bleeding, and intracranial hemorrhage by approximately 50% 1
• Eliminate INR monitoring requirements 1
• Have fewer drug interactions 2

Dose Reduction Considerations When Combined with Antiplatelet Therapy

For patients at high bleeding risk during the dual therapy period, consider reduced-dose DOAC 1:

• Rivaroxaban 15 mg daily (instead of 20 mg) for the duration of concomitant antiplatelet therapy 1
• Dabigatran 110 mg twice daily (instead of 150 mg) for the duration of concomitant antiplatelet therapy 1

These dose reductions apply only during the period of combined antithrombotic therapy and should be increased to standard doses once antiplatelet therapy is discontinued 1

Standard DOAC Dosing (Monotherapy Phase)

After discontinuing antiplatelet therapy, use standard therapeutic doses:

• Apixaban 5 mg twice daily (2.5 mg twice daily if ≥2 of: age ≥80, weight ≤60 kg, creatinine ≥1.5 mg/dL) 1
• Rivaroxaban 20 mg daily (15 mg if CrCl 30-49 mL/min) 1
• Dabigatran 150 mg twice daily (110 mg twice daily if age ≥80 or high bleeding risk) 1
• Edoxaban 60 mg daily (30 mg if weight ≤60 kg, CrCl 30-50 mL/min, or on certain P-glycoprotein inhibitors) 1

Timing of DOAC Re-initiation After PCI

Resume the DOAC on the same day as PCI or the following morning once hemostasis at the access site is secure 1

• Do not use heparin bridging when restarting the DOAC, as it increases bleeding without proven benefit 2, 3
• If the patient was on warfarin pre-procedure, aspirin may be continued until INR reaches 2.0-2.5, then discontinued 1
• For patients at very high stroke risk (recent thromboembolism within 3 months), consider bridging with low-molecular-weight heparin until therapeutic anticoagulation is re-established, but this is rarely necessary with DOACs 1

Bleeding Risk Mitigation

Mandatory Interventions

• Prescribe a proton pump inhibitor for all patients on combined antithrombotic therapy 1, 3
• Assess renal function before initiating therapy and monitor regularly (every 3-6 months) to adjust DOAC dosing 2, 3
• Use radial access for PCI rather than femoral access to reduce access-site bleeding 1

High Bleeding Risk Criteria

Patients meeting ≥1 major or ≥2 minor Academic Research Consortium criteria are at high bleeding risk 1:

Major criteria:

• Age ≥75 years
• Anticipated long-term anticoagulation (inherent to this scenario)
• Severe/end-stage chronic kidney disease (eGFR <30 mL/min)
• Hemoglobin <11 g/dL
• Spontaneous bleeding requiring hospitalization within 6 months
• Chronic bleeding diathesis
• Active malignancy within 12 months
• Previous spontaneous intracranial hemorrhage
• Brain arteriovenous malformation
• Moderate/severe ischemic stroke within 6 months

Minor criteria:

• Chronic kidney disease (eGFR 30-59 mL/min)
• Hemoglobin 11-12.9 g/dL (men) or 11-11.9 g/dL (women)
• Spontaneous bleeding requiring hospitalization within 12 months
• Baseline thrombocytopenia (<100×10⁹/L)
• Liver cirrhosis with portal hypertension
• Any ischemic stroke not meeting major criteria
• Traumatic intracranial hemorrhage within 12 months

For high bleeding risk patients, strongly favor the shortened triple therapy duration (≤1 week) and consider reduced-dose DOAC during dual therapy 1

Critical Pitfalls to Avoid

• Never use prasugrel or ticagrelor as part of triple or dual therapy with anticoagulation – these potent P2Y12 inhibitors are contraindicated when combined with anticoagulation due to excessive bleeding 1
• Never continue triple therapy beyond 4 weeks except in the rarest high-risk scenarios – the bleeding risk outweighs any ischemic benefit 1
• Never use warfarin when a DOAC is available and not contraindicated – DOACs have superior safety profiles 1, 2
• Never bridge with heparin when starting or resuming a DOAC – this practice increases bleeding without reducing thrombotic events 2, 3
• Never assume the patient needs lifelong antiplatelet therapy after 12 months – the DOAC alone provides adequate protection once the high-risk post-ACS period has passed 1
• Never give vitamin K to reverse a DOAC – it is ineffective for DOACs and only works for warfarin 1
• Never withhold the DOAC during PCI unless life-threatening bleeding occurs – continue it and add procedural anticoagulation 1