Thienopyridine Irreversible Platelet P2Y12 Receptor Antagonist (Prevents the Binding of ADP to the P2Y12 Receptor) (see Platelet P2Y12 Receptor Antagonists)
ADP is Released from Platelet Dense Granules and Normally Binds to Both the P2Y1 and P2Y12 Receptors
P2Y1: Gq-coupled receptor which mediates ADP-induced platelet aggregation through the stimulation of phospholipase C and the phosphatidylinositol-signaling pathway
P2Y12: Gi-coupled seven-transmembrane domain receptor which mediates ADP-induced platelet activation by inhibiting the adenylate cyclase-mediated signaling pathway, decreasing intracellular cAMP, inhibition of PI3K, induction of Akt kinase activation
P2Y12 is also involved in platelet secretion induced by various agonists
Recommendations for Periprocedural/Perioperative Management of Clopidogrel (American College of Chest Physicians Clinical Practice Guideline for the Perioperative Management of Antithrombotic Therapy) (Chest, 2022) [MEDLINE]
Minor Procedures (Dental, Dermatologic, Ophthalmologic)
In Patients Receiving an Antiplatelet Drug (Aspirin or P2Y12 Inhibitor) Who are Undergoing a Minor Dental Procedure, Continue the Antiplatelet Drug (Aspirin or P2Y12 Inhibitor) (Conditional Recommendation, Very Low Certainty of Evidence)
Patients Who are Receiving Dual Antiplatelet Therapy with Aspirin and a P2Y12 Inhibitor Can Continue Aspirin and Interrupt the P2Y12 Inhibitor
In Patients Receiving an Antiplatelet drug (ASA or P2Y12 inhibitor) Who are Undergoing a Minor Dermatologic Procedure, Continue the Antiplatelet Drug (Aspirin or P2Y12 inhibitor) (Conditional Recommendation, Very Low Certainty of Evidence)
Patients Who are Receiving Dual Antiplatelet Therapy with Aspirin and a P2Y12 Inhibitor Can Continue Aspirin and Interrupt the P2Y12 Inhibitor
In Patients Receiving an Antiplatelet drug (ASA or P2Y12 inhibitor) Who are Undergoing a Minor Ophthalmologic Procedure, Continue the Antiplatelet Drug (Aspirin or P2Y12 inhibitor) Throughout the Ophthalmologic Procedure (Conditional Recommendation, Low Certainty of Evidence)
Patients Who are Receiving Dual Antiplatelet Therapy with Aspirin and a P2Y12 Inhibitor Can Continue Aspirin and Interrupt the P2Y12 Inhibitor
Elective Non-Cardiac Surgery
In Patients Receiving Clopidogrel Who are Undergoing an Elective Non-Cardiac Surgery, Stop Clopidogrel 5 Days (as Opposed to 7-10 Days) Before Surgery (Conditional Recommendation, Very Low Certainty of Evidence)
Recommendation May Be Modified on a Case-by-Case Basis, Depending on Individual Patient Circumstances (Such as Surgery-Related Bleeding Risk)
Elective Surgery
In Patients Receiving Antiplatelet Drug Therapy Who are Undergoing an Elective Procedure/Surgery, Routine Use of Platelet Function Testing Prior to Procedure/Surgery is Not Recommended (Conditional Recommendation, Very Low Certainty of Evidence)
Platelet Function Testing Could Be Used with a Possible Small Benefit and Little Harm in Certain Scenarios Such as Patients Undergoing Coronary Artery Bypass Graft (CABG) Surgery Who Have Recently Started Taking a P2Y12 Inhibitor
Costs Would Be Moderate for Implementation
In Patients Who Require Antiplatelet Drug Interruption for an Elective Procedure/Surgery, Resume Antiplatelet Drugs in ≤24 hrs (Instead of >24 hrs) After the Procedure/Surgery (Conditional Recommendation, Very Low Certainty of Evidence)
In Patients Receiving ASA and a P2Y12 Inhibitor with Coronary Stents Placed within the Last 6-12 wks Who are Undergoing an Elective Procedure/Surgery, Continuation Both Antiplatelet Agents or Stop One Antiplatelet Agent within 7-10 Days of Procedure/Surgery (Conditional Recommendation, Very Low Certainty of Evidence)
Either Approach is Reasonable Depending on the Bleeding Risk Associated with the Procedure/Surgery if Antiplatelet Therapy is Continued and Risk for Acute Coronary Syndrome/Coronary Stent Thrombosis if Antiplatelet Therapy is Interrupted
The Following Factors Will Weigh in the Decision About Whether to Continue Dual Antiplatelet Therapy or Interrupt One Agent
Timing of Stent Placement (Whether Closer to 6 wks or 12 wks)
Type of Stent (Drug-Eluting or Bare-Metal)
Location of the Stent (Whether at a Dominant Coronary Artery or Not)
Number and length of Stents Implanted
In Patients Receiving ASA and a P2Y12 Who Had Coronary Stents Placed within the Last 3-12 mos and are Undergoing an Elective Procedure/Surgery, Stop the P2Y12 Inhibitor Prior to Procedure/Surgery (as Opposed to Continuing the P2Y inhibitor (Conditional Recommendation, Very Low Certainty of Evidence)
Recommendation is Based on Indirect Evidence and Expert-Based Consensus that Stopping P2Y12 Inhibitors in Patients with Stents > 3 mos Postimplantation is Likely Safe
The Following Factors Will Weigh in the Decision About Whether to Interrupt the P2Y12 inhibitor
Timing of Stent Placement (Whether Closer to 3 mos or 12 mos)
Type of Stent (Drug-Eluting or Bare-Metal)
Location of the Stent (Whether at a Dominant Coronary Artery or Not)
Number and length of Stents Implanted
In Patients with Coronary Stents Who Require Interruption of Antiplatelet Drugs for an Elective Procedure/Surgery, Routine Bridging Therapy with a Glycoprotein IIb-IIIa Inhibitor, Cangrelor, or Low Molecular Weight Heparin is Not Recommended (Conditional Recommendation, Low Certainty of Evidence)
Bridging Approach May Be Considered in Selected High-Risk Patients (Those with Coronary Stent Placed within 3 mos in a Critical Location
In Patients with Coronary Stents Who Require Continued Dual Antiplatelet Therapy, Delaying an Elective Procedure/Surgery is Recommended (Conditional Recommendation, Very Low Certainty of Evidence)
Duration of Procedure/Surgery Delay is Addressed on a Case-by-Case Basis and Should Consider the Urgency of the Procedure/Surgery, the Time Elapsed Since Coronary Stenting, and the Risk Profile of the Coronary Stenting (Critical Location, Multiple Stents, etc)
In Patients Receiving a P2Y12 Inhibitor Drug (Clopidogrel, Prasugrel, Ticagrelor) and Undergoing Coronary Artery Bypass Graft (CABG) Surgery, Stop the P2Y12 Inhibitor Perioperatively (Conditional Recommendation, Low Certainty of Evidence)
Stop Prasugrel for a Period of 7 Days Preoperatively
Stop Clopidogrel for a Period of 5 Days Preoperatively
Stop Ticagrelor for a Period of 3-5 Days Preoperatively
In Patients Receiving ASA or a P2Y12 Inhibitor Who are Undergoing Coronary Artery Bypass Graft (CABG) Surgery, Resume the ASA or the P2Y12 Inhibitor in ≤24 hrs (as Opposed to ≥24 hours) After Surgery (Conditional Recommendation, Low Certainty of Evidence)
Resumption of Antiplatelet Therapy May Be Delayed in Patients Who Develop Post-CABG Thrombocytopenia (Platelet Count < 50k), Typically Occurring with On-Pump Surgery
Periprocedural/Perioperative Management of Clopidogrel
Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):7S-47S. doi: 10.1378/chest.1412S3 [MEDLINE]
Perioperative Management of Antithrombotic Therapy: An American College of Chest Physicians Clinical Practice Guideline. Chest. 2022 Aug 11;S0012-3692(22)01359-9. doi: 10.1016/j.chest.2022.07.025 [MEDLINE]
Adverse Effects
Diffuse Alveolar Hemorrhage After Clopidogrel Use. J Invasive Cardiol. 2001;13(7)
