Preoperative Aspirin and Postoperative Antiplatelets in Coronary Artery Bypass Grafting: The PAPA CABG Study

BACKGROUND: Platelets play a central role in the pathogenesis of ischemic complications (coronary artery bypass graft occlusion, myocardial infarction, stroke) following CABG surgery. Aspirin and clopidogrel used alone or in combination are effective for preventing ischemic complications in a broad range of high risk patients. However aspirin is usually discontinued before CABG surgery because of concerns about bleeding while the combination of aspirin and clopidogrel has not been evaluated for preventing ischemic complications after CABG surgery.

OBJECTIVES: The overall objectives of our research are to compare the effectiveness and safety of aspirin vs placebo before bypass surgery, and clopidogrel plus aspirin vs aspirin alone after surgery, on:

• blockage of coronary artery bypass grafts, MI, stroke, or death at 30 days
• bleeding and need for transfusion after surgery The specific objective of the present pilot study is to demonstrate the feasibility of recruiting patients undergoing CABG surgery into this study and of performing CT angiography at 30 days to determine graft patency. We will also measure the effect of different antiplatelet treatments on platelet function and blood markers of systemic inflammation during the first 48 hours after surgery.

DESIGN: This is a 2x2 factorial study of 150 elective CABG patients who will be randomized to receive low dose aspirin (81mg/d) or placebo for 5 days prior to surgery and aspirin 325mg loading dose followed by 81 mg/d plus clopidogrel 75 mg/d versus aspirin 81 mg/d and placebo post operatively.

OUTCOME: graft patency measured by CT angiography, MI, stroke, death, bleeding, transfusion requirement, need for re-exploration surgery, and laboratory measures of platelet function and aspirin resistance (including 11-dehydro thromboxane B2).

SAMPLE SIZE: This is a pilot study designed primarily to demonstrate feasibility. We propose to recruit a total of 150 patients over a 12 month period (2-4 per week).

Inclusion criteria

• Patients 18 years of age or older
• Undergoing on-pump, elective coronary artery bypass grafting with at least 2 free grafts
• Patient able to give informed consent

Exclusion criteria

• planned date of surgery is <5 days from planned recruitment date
• patient has clear indication for anticoagulation (eg. mechanical heart valve, atrial fibrillation) or ADP receptor antagonist (eg. drug-eluting stent)
• allergy to or intolerance of aspirin or clopidogrel
• history of bleeding diathesis, significant GI bleed, ICH, or liver failure
• Patient has known renal failure or contraindication for Cardiac CT Angio
• Patient has had previous cardiac surgery