What is the recommended dual anti-platelet therapy (DAPT) regimen for a patient who has undergone Coronary Artery Bypass Grafting (CABG) to improve graft patency?

Dual Antiplatelet Therapy After CABG to Improve Graft Patency

For patients with acute coronary syndrome (ACS) undergoing CABG, resume P2Y12 inhibitor therapy postoperatively and continue for 12 months total from the ACS event (aspirin 75-100 mg daily plus clopidogrel, ticagrelor, or prasugrel); for stable ischemic heart disease (SIHD) patients, DAPT with clopidogrel for 12 months may be reasonable to improve vein graft patency, though the evidence is weaker and bleeding risk must be carefully weighed. 1, 2

Clinical Context Determines DAPT Strategy

The recommendation for DAPT after CABG fundamentally depends on whether the patient has ACS or SIHD:

ACS Patients (NSTEMI, STEMI, Unstable Angina)

• Resume P2Y12 inhibitor postoperatively as soon as hemostasis is secured (typically 24-48 hours) and continue to complete 12 months of DAPT from the ACS event (Class I, Level C-LD recommendation) 1, 3
• The 12-month duration is calculated from the ACS event, not from the surgery date—this is a critical distinction to avoid premature discontinuation 3
• Aspirin 75-100 mg daily should be continued throughout the perioperative period and indefinitely 1, 3
• The CURE study demonstrated reduction in ischemic events in ACS patients treated with aspirin plus clopidogrel who underwent CABG, with benefit observed primarily before the procedure 1
• Danish registry data showed significantly fewer deaths during mean follow-up in CABG patients treated with aspirin plus clopidogrel versus aspirin alone after ACS 1, 3

SIHD Patients (Stable Coronary Disease)

• DAPT with clopidogrel initiated early postoperatively for 12 months may be reasonable to improve vein graft patency (Class IIb, Level B-NR recommendation) 1, 2
• This is a weaker recommendation than for ACS patients, reflecting more equivocal evidence 2
• The European Society of Cardiology explicitly states that DAPT is NOT routinely indicated after CABG for chronic coronary syndromes, but may be considered in selected cases at increased risk of graft occlusion who are NOT at high bleeding risk 4
• Aspirin monotherapy (75-100 mg daily) remains the standard of care for most SIHD patients after CABG 4

Evidence for Graft Patency Benefit

The evidence supporting DAPT for graft patency shows mixed but generally favorable results:

• Meta-analysis of 5 RCTs and 6 observational studies demonstrated that DAPT was associated with reduced vein graft occlusion and 30-day mortality compared to aspirin monotherapy 1, 2
• A meta-analysis of only the 5 RCTs showed DAPT was associated with significantly lower vein graft occlusion at 1 year versus aspirin monotherapy, but with no improvement in arterial graft patency 1
• In the only RCT to specifically demonstrate benefit, vein graft patency at 3 months after CABG was significantly higher in patients treated with clopidogrel and aspirin (100 mg) than in those receiving aspirin monotherapy 1, 2
• A 2018 meta-analysis of 8 RCTs and 9 observational studies (11,135 patients) found graft occlusion was reduced with DAPT (11.3% vs 14.2%, RR 0.79) 5
• The same meta-analysis showed DAPT reduced major adverse cardiac events (10.3% vs 12.1%, RR 0.84) and all-cause mortality (5.7% vs 7.0%, RR 0.67) without significantly increasing major bleeding 5

Off-Pump vs On-Pump CABG Considerations

• Benefits of DAPT appear more pronounced in off-pump CABG patients, with improved graft patency noted in observational studies and RCTs 1
• In pooled analysis of off-pump CABG studies, DAPT reduced perioperative MI by 68% and saphenous graft occlusion by 55% compared to aspirin alone 6
• Several studies of predominantly on-pump CABG did not demonstrate differences in graft patency between aspirin monotherapy and DAPT at follow-up ranging from 1 month to 1 year 1

Choice of P2Y12 Inhibitor

Clopidogrel

• Clopidogrel 75 mg daily is the most studied agent in CABG patients and appropriate for most situations 3
• If DAPT is used in SIHD, clopidogrel should be added to aspirin with duration of 6-12 months 4

Ticagrelor

• May be preferred over clopidogrel in ACS patients based on post-hoc analysis from the PLATO study showing significant reduction in cardiovascular mortality compared to clopidogrel in CABG patients 1, 3
• However, ticagrelor carries higher bleeding risk than clopidogrel when taken within 24 hours before CABG (33.3% surgical re-exploration rate vs 2.56% with clopidogrel) 7

Prasugrel

• Showed significantly lower 30-day mortality than clopidogrel in CABG patients from TRITON-TIMI 38, but with more postoperative blood loss 1, 3
• Should be discontinued at least 7 days prior to any surgery when possible 8
• Consider lowering maintenance dose to 5 mg in patients <60 kg due to increased bleeding risk 8

Bleeding Risk Management

Major bleeding after surgery is more frequent with DAPT compared to aspirin monotherapy 1, 2

Risk Mitigation Strategies:

• Add a proton pump inhibitor in patients at increased GI bleeding risk (elderly, history of GI bleeding, chronic NSAID users) 3
• Consider discontinuation of P2Y12 inhibitor after 6 months in CABG patients with prior MI and high bleeding risk (PRECISE-DAPT ≥25) 3
• In patients with high bleeding risk (oral anticoagulation, major intracranial surgery) or significant overt bleeding, discontinuation of P2Y12 inhibitor after 3 months may be reasonable 1
• A 2013 meta-analysis showed trend toward higher incidence of major bleeding with DAPT (RR 1.17,95% CI 1.00-1.37, p = 0.05) 6

Timing of Discontinuation Before CABG:

• For elective CABG, discontinue prasugrel ≥7 days before, clopidogrel ≥5 days before, ticagrelor ≥3 days before 3
• DAPT ongoing until 1 day before CABG showed significantly increased risk of bleeding complications compared to discontinuation at 2-3 or >3-4 days before 7
• Continue aspirin through the perioperative period 3

Critical Pitfalls to Avoid

• Do not fail to resume P2Y12 inhibitor postoperatively in ACS patients—this is a Class I recommendation critical for reducing mortality and cardiovascular events 3
• Do not discontinue P2Y12 inhibitor prematurely after CABG in ACS patients—the 12-month duration is calculated from the ACS event, not the surgery date 3
• Do not delay aspirin initiation beyond 48 hours postoperatively—this eliminates the graft patency benefit 4
• Do not routinely use DAPT in stable CCS patients without additional risk factors—the bleeding risk outweighs benefits in most cases 4
• Do not assume all P2Y12 inhibitors have equivalent bleeding profiles—ticagrelor within 24 hours of surgery carries substantially higher bleeding risk than clopidogrel 7

Practical Algorithm

Step 1: Identify Clinical Context

• ACS (NSTEMI/STEMI/UA) → Proceed to Step 2
• SIHD without recent ACS → Proceed to Step 3

Step 2: ACS Patients

• Start aspirin 75-100 mg daily (continue indefinitely)
• Resume P2Y12 inhibitor 24-48 hours postoperatively when hemostasis secured
• Continue DAPT for 12 months from ACS event
• Preferred P2Y12 inhibitor: ticagrelor > clopidogrel (based on mortality benefit) 3
• If high bleeding risk develops: consider stopping P2Y12 inhibitor at 6 months 3

Step 3: SIHD Patients

• Start aspirin 75-100 mg daily (continue indefinitely) 4
• Consider adding clopidogrel 75 mg daily for 12 months if:
  • Patient at increased risk of graft occlusion AND
  • NOT at high bleeding risk 2, 4
• If high bleeding risk: aspirin monotherapy only 4