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Management of Antiplatelet Therapy in Patients with Coronary Stents Undergoing Noncardiac Surgery

      In clinical practice, significant variability exists with regard to the timing of elective noncardiac surgery after percutaneous coronary intervention (PCI) and the perioperative management of antiplatelet therapy.
      • Childers CP
      • Maggard-Gibbons M
      • Ulloa JG
      • et al.
      Perioperative management of antiplatelet therapy in patients undergoing non-cardiac surgery following coronary stent placement: a systematic review.
      Although coronary revascularization should not be performed with the intent to reduce perioperative risks of noncardiac surgery,
      • McFalls EO
      • Ward HB
      • Moritz TE
      • et al.
      Coronary-artery revascularization before elective major vascular surgery.
      up to 20% of the patients who have undergone PCI undergo noncardiac surgery within 2 years; 3.5% to 7.5% of these surgeries occur within 6 months of PCI.
      • Smilowitz NR
      • Lorin J
      • Berger JS
      Risks of noncardiac surgery early after percutaneous coronary intervention.
      ,
      • Smilowitz NR
      • Berger JS
      Perioperative Cardiovascular Risk Assessment And Management For Noncardiac Surgery.
      Noncardiac surgery in patients with coronary stents is associated with increased risk for perioperative ischemic and bleeding complications. Interruption of dual antiplatelet therapy (DAPT) in the hypercoagulable and proinflammatory perioperative state can promote coronary stent thrombosis and lead to myocardial infarction, while continuation of antiplatelet therapy increases surgical bleeding risks. In patients who underwent noncardiac surgery within 6 months of PCI, myocardial infarction and bleeding were reported in 4.7% and 32.0%, respectively.
      • Smilowitz NR
      • Lorin J
      • Berger JS
      Risks of noncardiac surgery early after percutaneous coronary intervention.
      To reduce perioperative risks of noncardiac surgery in patients with coronary stents, surgical teams, anesthesiologists, and cardiovascular disease specialists should discuss the urgency of the procedure, the planned surgical approach (minimally invasive vs open), the anticipated hemodynamic changes and blood loss, and determine if and when antiplatelet therapy may be safely interrupted.
      • Smilowitz NR
      • Berger JS
      Perioperative Cardiovascular Risk Assessment And Management For Noncardiac Surgery.
      The American College of Cardiology/American Heart Association (2016), the American Society of Regional Anesthesia (2018), the European Society of Cardiology/European Society of Anesthesiology (2014), and the American College of Chest Physicians (2012) guidelines recommend delaying elective noncardiac surgery for ≥4-6 weeks after bare-metal stent PCI and ≥6-12 months after drug eluting stent (DES)-PCI.
      • Levine GN
      • Bates ER
      • Bittl JA
      • et al.
      2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease.
      • Kristensen SD
      • Knuuti J
      • Saraste A
      • et al.
      2014 ESC/ESA Guidelines on non-cardiac surgery: cardiovascular assessment and management.
      • Douketis JD
      • Spyropoulos AC
      • Spencer FA
      • et al.
      Perioperative management of antithrombotic therapy.
      • Horlocker TT
      • Vandermeuelen E
      • Kopp SL
      • Gogarten W
      • Leffert LR
      • Benzon HT
      Regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy: American Society of Regional Anesthesia and Pain Medicine evidence-based guidelines (fourth edition).
      Urgent noncardiac surgery performed 3-6 months after DES-PCI may be reasonable in selected cases, if the risk of delaying noncardiac surgery is greater than the expected risk of stent thrombosis (American College of Cardiology/American Heart Association Class IIb recommendation, Level of evidence C).
      • Levine GN
      • Bates ER
      • Bittl JA
      • et al.
      2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease.
      However, noncardiac surgery is not advised within the first 3 months after DES-PCI, irrespective of the stent type.
      • Levine GN
      • Bates ER
      • Bittl JA
      • et al.
      2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease.
      ,
      • Kristensen SD
      • Knuuti J
      • Saraste A
      • et al.
      2014 ESC/ESA Guidelines on non-cardiac surgery: cardiovascular assessment and management.

      Predictors of Stent Thrombosis

      Clinical, anatomic, and stent characteristics impact the risks of stent thrombosis after DES-PCI. Factors associated with high risk of stent thrombosis include early interruption of antiplatelet therapy, acute coronary syndrome as the indication for PCI, prior stent thrombosis, complex PCI with bifurcation disease, multiple stents or long stented segments, in-stent restenosis, and small stent diameters.
      • Smilowitz NR
      • Berger JS
      Perioperative Cardiovascular Risk Assessment And Management For Noncardiac Surgery.
      ,
      • Cao D
      • Chandiramani R
      • Capodanno D
      • et al.
      Non-cardiac surgery in patients with coronary artery disease: risk evaluation and periprocedural management.
      Age ≥60 years, multiple prior myocardial infarctions, acute coronary syndrome in the past year, estimated glomerular filtration rate less than 60 mL/min, diabetes mellitus, left ventricular ejection fraction <40%, and hemoglobin less than 10 g/dL may also indicate higher thrombotic risk.
      • Smilowitz NR
      • Berger JS
      Perioperative Cardiovascular Risk Assessment And Management For Noncardiac Surgery.
      ,
      • Cao D
      • Chandiramani R
      • Capodanno D
      • et al.
      Non-cardiac surgery in patients with coronary artery disease: risk evaluation and periprocedural management.

      Antiplatelet Therapy Management

      Newer generations of coronary stents are associated with lower risks of stent thrombosis compared to the first-generation DES. In the nonsurgical setting, shorter durations of DAPT (aspirin 75-100 mg/d with a P2Y12 inhibitor such as clopidogrel, ticagrelor, or prasugrel) ranging from 1-3 months (instead of ≥6-12 months) followed by P2Y12 inhibitor monotherapy may be reasonable among patients at high bleeding risk who receive newer-generation DES, but the safety of this approach in the setting of noncardiac surgery is unknown.
      • Knijnik L
      • Fernandes M
      • Rivera M
      • et al.
      Meta-analysis of duration of dual antiplatelet therapy in acute coronary syndrome treated with coronary stenting.
      In most patients with coronary stents, aspirin should be continued throughout the perioperative period.
      • Levine GN
      • Bates ER
      • Bittl JA
      • et al.
      2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease.
      ,
      • Kristensen SD
      • Knuuti J
      • Saraste A
      • et al.
      2014 ESC/ESA Guidelines on non-cardiac surgery: cardiovascular assessment and management.
      This recommendation is based on a subgroup analysis of 470 patients with prior PCI in the PeriOperative ISchemic Evaluation-2 (POISE-2) trial, in which aspirin reduced the risk of death or nonfatal myocardial infarction compared to placebo (6.0% vs 11.5%). No increase in major and life-threatening bleeding was observed with aspirin in this subgroup analysis, although the event rates were low.
      • Graham MM
      • Sessler DI
      • Parlow JL
      • et al.
      Aspirin in patients with previous percutaneous coronary intervention undergoing noncardiac surgery.
      Aspirin (<200 mg/d) is also not a contraindication for neuraxial procedures.
      • Kietaibl S
      • Ferrandis R
      • Godier A
      • et al.
      Regional anaesthesia in patients on antithrombotic drugs.
      If the anticipated surgical bleeding risk is exceptionally high (eg, intracranial, intraspinal, or certain ophthalmological procedures), guidelines recommend that aspirin be discontinued for at least 7 days prior to the procedure.
      • Kristensen SD
      • Knuuti J
      • Saraste A
      • et al.
      2014 ESC/ESA Guidelines on non-cardiac surgery: cardiovascular assessment and management.
      ,
      • Douketis JD
      • Spyropoulos AC
      • Spencer FA
      • et al.
      Perioperative management of antithrombotic therapy.
      However, withholding aspirin for a shorter time period may be acceptable because the time to normalization of platelet inhibition after stopping aspirin is 3-4 days.
      • Nagalla S
      • Sarode R
      Role of platelet transfusion in the reversal of anti-platelet therapy.
      In patients at high thrombotic risk undergoing low bleeding risk procedures, P2Y12 inhibitors may be continued in the perioperative period. Interruption of P2Y12 inhibitor is recommended in surgeries associated with intermediate or high bleeding risks and prior to neuraxial procedures.
      • Levine GN
      • Bates ER
      • Bittl JA
      • et al.
      2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease.
      ,
      • Kristensen SD
      • Knuuti J
      • Saraste A
      • et al.
      2014 ESC/ESA Guidelines on non-cardiac surgery: cardiovascular assessment and management.
      ,
      • Horlocker TT
      • Vandermeuelen E
      • Kopp SL
      • Gogarten W
      • Leffert LR
      • Benzon HT
      Regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy: American Society of Regional Anesthesia and Pain Medicine evidence-based guidelines (fourth edition).
      ,
      • Kietaibl S
      • Ferrandis R
      • Godier A
      • et al.
      Regional anaesthesia in patients on antithrombotic drugs.
      In these instances, withholding clopidogrel and ticagrelor for 5 days prior to the surgery, and prasugrel for 7 days prior to the surgery is recommended.
      • Kristensen SD
      • Knuuti J
      • Saraste A
      • et al.
      2014 ESC/ESA Guidelines on non-cardiac surgery: cardiovascular assessment and management.
      Surgical bleeding risks of noncardiac surgery in the setting of P2Y12 inhibitor monotherapy versus aspirin monotherapy are not well defined.
      If DAPT is interrupted prior to the surgery, bridging therapy with low-molecular-weight heparin is not recommended because it confers additional bleeding risk without mitigating the platelet-driven mechanism of stent thrombosis.
      • Kristensen SD
      • Knuuti J
      • Saraste A
      • et al.
      2014 ESC/ESA Guidelines on non-cardiac surgery: cardiovascular assessment and management.
      ,
      • Banerjee S
      • Angiolillo DJ
      • Boden WE
      • et al.
      Use of antiplatelet therapy/DAPT for post-PCI patients undergoing noncardiac surgery.
      In the rare circumstance where the risk of stent thrombosis is exceptionally high (eg, urgent noncardiac surgery within 1 month of PCI) and DAPT cannot be safely continued due to intra- and postoperative bleeding risks, a short-acting P2Y12 inhibitor such as cangrelor or short-acting intravenous platelet glycoprotein IIb/IIIa receptor-blockers such as tirofiban or eptifibatide, can be considered for bridging therapy prior to surgery in place of oral therapy, but there are no randomized clinical trial data to support the safety and efficacy of this approach.
      • Banerjee S
      • Angiolillo DJ
      • Boden WE
      • et al.
      Use of antiplatelet therapy/DAPT for post-PCI patients undergoing noncardiac surgery.
      There is no reliable evidence that a rebound increase in platelet aggregation occurs with abrupt discontinuation of aspirin or P2Y12 inhibitors.
      • Banerjee S
      • Angiolillo DJ
      • Boden WE
      • et al.
      Use of antiplatelet therapy/DAPT for post-PCI patients undergoing noncardiac surgery.
      Perioperative bleeding after noncardiac surgery is a significant concern. Platelet transfusion may be considered in patients on antiplatelet therapies for the prophylaxis or management of perioperative bleeding, but the efficacy is uncertain.
      • Nagalla S
      • Sarode R
      Role of platelet transfusion in the reversal of anti-platelet therapy.
      Furthermore, platelet transfusions may be ineffective at restoring platelet activity within 24 hours of ticagrelor, a reversible P2Y12 inhibitor.
      • Nagalla S
      • Sarode R
      Role of platelet transfusion in the reversal of anti-platelet therapy.
      Tranexamic acid reduces perioperative bleeding, but the safety of this therapy in patients with coronary stents remains uncertain.
      • Devereaux PJ
      • Marcucci M
      • Painter TW
      • et al.
      Tranexamic acid in patients undergoing noncardiac surgery.
      Platelet function testing to predict perioperative bleeding risks and guide the timing of noncardiac surgery has not been studied in clinical trials.
      • Cao D
      • Chandiramani R
      • Capodanno D
      • et al.
      Non-cardiac surgery in patients with coronary artery disease: risk evaluation and periprocedural management.
      Novel approaches for prediction and management of perioperative risk of bleeding and thrombosis are necessary to reduce complications.
      Postoperatively, oral antiplatelet therapy should be resumed as soon as permissible (within 24-72 hours if possible), based on the anticipated surgical bleeding risks, while carefully balancing the risks of stent thrombosis and postoperative myocardial ischemia. Ideally, after an interruption, antiplatelet agents should be resumed with a postoperative loading dose, as bleeding risks permit, to ensure rapid resumption of platelet inhibition.

      Conclusions

      During preoperative evaluation, providers should carefully assess thrombotic risks based on the clinical and anatomical characteristics of patients with coronary stents and the type of stents. Thrombotic and bleeding risks should guide the decisions on timing of nonemergent noncardiac surgery in these patients. Cardiovascular disease specialists should be involved in the perioperative care of patients at high thrombotic risk and guide decisions on perioperative management of antiplatelet therapy. Unless contraindicated due to extreme surgical bleeding risks, antiplatelet monotherapy (usually aspirin) should be continued in the perioperative period in patients with coronary stents. Thoughtful, coordinated care of patients with coronary stents is important to reduce the incidence of perioperative myocardial ischemic events.

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