When to restart Plavix (clopidogrel) postoperatively?

From the Guidelines

Plavix (clopidogrel) should typically be restarted 24-48 hours after surgery, once adequate hemostasis has been achieved and the risk of bleeding has decreased. For patients undergoing high bleeding risk procedures, waiting 48-72 hours may be necessary. The decision should be individualized based on the patient's thrombotic risk, the type of surgery performed, and the observed postoperative bleeding. For patients with recent coronary stents, particularly drug-eluting stents placed within the last 6-12 months, earlier resumption (within 24 hours if possible) is preferred to reduce the risk of stent thrombosis, as suggested by the American College of Chest Physicians clinical practice guideline 1.

The standard dose when restarting is 75 mg daily, though some high-risk patients may receive a loading dose of 300-600 mg if rapid platelet inhibition is needed. Coordination between the surgeon, cardiologist, and anesthesiologist is essential to balance bleeding and thrombotic risks, as emphasized in the management of antiplatelet therapy in patients undergoing elective invasive procedures 1. Plavix works by irreversibly inhibiting platelet P2Y12 receptors, preventing platelet aggregation, which is why timing of resumption is critical - too early increases bleeding risk while delayed restart increases thrombotic risk.

Some studies have reported a higher risk of major bleeding and need for transfusion requirements in patients who received clopidogrel within 5 days before CABG surgery 1, which supports the recommendation to delay resumption of Plavix until 24-48 hours after surgery. However, for patients with recent coronary stents, the risk of stent thrombosis must be balanced against the risk of bleeding, and earlier resumption of Plavix may be necessary, as suggested by the 2011 ACCF/AHA guideline for coronary artery bypass graft surgery 1.

Key considerations in determining the timing of Plavix resumption include:

• The type of surgery performed and the associated bleeding risk
• The patient's thrombotic risk, including the presence of recent coronary stents
• The observed postoperative bleeding and the achievement of adequate hemostasis
• The need for coordination between the surgeon, cardiologist, and anesthesiologist to balance bleeding and thrombotic risks.

From the FDA Drug Label

5.3 Discontinuation of Clopidogrel Discontinuation of clopidogrel increases the risk of cardiovascular events. If clopidogrel must be temporarily discontinued (e.g., to treat bleeding or for surgery with a major risk of bleeding), restart it as soon as possible. When possible, interrupt therapy with clopidogrel for five days prior to such surgery. Resume clopidogrel as soon as hemostasis is achieved.

Restarting Plavix (clopidogrel) postoperatively:

• Restart as soon as possible after temporary discontinuation for surgery
• Resume as soon as hemostasis is achieved 2

From the Research

Timing of Plavix (Clopidogrel) Restart Postoperatively

• The optimal timing for restarting Plavix (clopidogrel) postoperatively is not explicitly stated in the provided studies, but the timing of discontinuation and resumption can be inferred from the study findings 3, 4, 5, 6, 7.
• According to the study by 4, clopidogrel should be resumed within 12-24 hours after the operation.
• The study by 6 mentions that clopidogrel was resumed immediately after surgery in their initial strategy, but later adopted a protocol of bridging high-risk patients with eptifibatide before surgery.

Discontinuation of Clopidogrel Before Surgery

• The study by 3 found that discontinuation of clopidogrel at least 72 hours before off-pump coronary artery bypass grafting (OPCAB) surgery resulted in a similar blood loss pattern compared to a control group not taking clopidogrel.
• The study by 5 found that discontinuation of clopidogrel 72-120 hours before surgery did not increase the incidence of major bleeding complications compared to discontinuation more than 120 hours before surgery, but this was not the case for ticagrelor.
• The study by 7 suggests that urgent or emergent coronary artery bypass grafting (CABG) can be safely performed in patients with haemoglobin levels above 110 g/L, even if clopidogrel is discontinued less than 5 days before surgery.

Perioperative Management of Clopidogrel

• The study by 4 provides guidelines for the perioperative management of patients on antiplatelet therapy, including clopidogrel, and recommends resuming clopidogrel within 12-24 hours after surgery.
• The study by 6 describes a protocol for bridging high-risk patients with eptifibatide before surgery, which may minimize the risk of cardiovascular events.