Antiplatelet Therapy and Cardiac Surgery: A Challenge? The use of aspirin and clopidogrel in cardiac surgery

Transcription

1 Jeroen De Haes Promotor: Dr. Poortmans Antiplatelet Therapy and Cardiac Surgery: A Challenge? The use of aspirin and clopidogrel in cardiac surgery

2 Overview Indications of DAPT Pharmacology Aspirin P2Y 12 Receptorblockers Perioperative use Benefit Risk Practical Recommendations

3 Indications for DAPT CHARISMA Trial: No benefit in primary prevention No benefit in stable CAD CURE trial: Benefit for NSTEMI or Unstable Angina without PCI CLARITY-TIMI 28 trial: Benefit of DAPT auxiliary to thrombolytics PCI-CURE trial/ CREDO trial: Benefit of DAPT for STEMI Multiple Trials/ FDA: BMS 1 years or at least 1 month DES: at least 1 year

4 Pharmacology: ASPIRIN COX- 1 inhibition Preventing platelet activation and aggregation Impair Secondary Haemostasis Influences interaction between platelets, neutrophils and erythrocytes Augments endothelial functions Aspirin inhibition of COX-1 decreases TXA2 production. Source: Gasparyan, A. Y. et al. J Am Coll Cardiol 2008;51:

5 Pharmacology: P2Y 12 Receptor Inhibitors General Preventing ADP binding to P2Y 12 Receptor Inhibition of activation, aggregation and thrombin generation Inhibition of CRP and TNF release Inhibition of platelet-neutrophil aggregates Clopidogrel Prodrug Slow onset and variable inhibition Prasugrel Prodrug More rapid and less variable inhibition Higher risk for bleeding Ticagrelor Reversible Fast onset and off-set More consistent inhibition Mahla E, Metzler H, Tantry U et al. Controversies in oral antiplatelet therapy in patients undergoing aortocoronary bypass surgery. The Annals of Thoracic Surgery 2010; 90(3):

6 Perioperative use of Aspirin: Benefits vs Risk BENEFITS Lower all cause mortality in secondary prevention Sung et al. Decrease in post-op MI after cardiac surgery and in-hospital mortality Hastings et al Cardioprotective effect immediately post-op in CABG setting RISKS Rebound Phenomenon Bieving et al./ Vial et al.: Dose dependent Increased risk of cardiovascular events O Riodan et al: Cessation has gloomy prognosis Increased bleeding risk POISE-2: 23% relative increase Burger et al: Increase bleeding complications, not severity

7 Perioperative use of Clopidogrel: Benefits vs Risk BENEFITS Reduction of cardiovascular ischemic events ACUITY trial: stopping clopidogrel 5 days before surgery Miceli et al: Time frame of 5 days RISKS Increased bleeding risk ACUITY trialdependent on timing of last dose CURRENT-OASIS 7:Effect of loading dose Increased Mortality and Post-op MI Siller-Matula et al: related to increased bleeding Vorobcsuk et al: similar results Miceli et al: cessation less then 5 days

8 Miceli A, Duggan SMJ, Aresu G, de Siena PM, Romeo F, Glauber M, et al. Combined clopidogrel and aspirin treatment up to surgery increases the risk of postoperative myocardial infarction, blood loss and reoperation for bleeding in patients undergoing coronary artery bypass grafting. Eur J Cardiothorac Surg [Internet]. 2013;43(June 2012):722 8

9 Miceli A, Duggan SMJ, Aresu G, de Siena PM, Romeo F, Glauber M, et al. Combined clopidogrel and aspirin treatment up to surgery increases the risk of postoperative myocardial infarction, blood loss and reoperation for bleeding in patients undergoing coronary artery bypass grafting. Eur J Cardiothorac Surg [Internet]. 2013;43(June 2012):722 8

10 Perioperative use of Prasugrel and Ticagrelor Prasugrel TRITON-TIMI 38: greater bleeding risk than clopidogrel group Lower 13 month mortality Ticagrelor PLATO trial: no raise in CABG related bleeding Lower rate of post CABG mortality Siller-Matula JM, Petre a., Delle-Karth G, Huber K, Ay C, Lordkipanidze M, et al. Impact of preoperative use of P2Y12 receptor inhibitors on clinical outcomes in cardiac and non-cardiac surgery: A systematic review and meta-analysis. Eur Hear J Acute Cardiovasc Care [Internet]. 2015

11 Practical recommendations: Cessation of drugs Aspirin: Continued in perioperative surgery except for high-bleeding risk surgeries ACC/AHA guideline: stop Aspirin 7-10days before cardiac surgery Guideline by European Journal of Cardio-Thoracic surgery: Stop aspirin 2-10 days before elective cardiac surgery Urgent cardiac surgery: continue aspirin up to the day of surgery Restart Aspirin as soon as possible post-operative Clopidogrel/Ticagrelor: Stop 5-7 days before elective cardiac surgery Urgent CAGB: stop 24hours if possible Bridging therapy with GP IIb/IIIa receptor inhibitors: requires further research Prasugrel: Stop 7-10 days before elective cardiac surgery

12 Practical recommendations: Reduction of blood loss Prophylatic Platelet transfusion Rapid reversal Risk of reversal of clinical benefit Use of Antifibrinolytics Aprotinin: renal dysfunction and end-organ damage Tranexamic acid: reduces blood loss, need for transfusion and re-operation Can be used safely In vitro platelet function testing: Additional studies recommended Recognizing patients had higher bleeding risk Fixing optimal window for surgery Predictive value and guide for transfusion

13 Cannon CP, Mehta SR, Aranki SF. Balancing the benefit and risk of oral antiplatelet agents in coronary artery bypass surgery.ann Thorac Surg [Internet]. 2005;80:

14 Questions & Discussion

15 References 1. Francesco F, FabianaR, AngiolilloDJ. Management of antiplatelet therapy in patients with coronary artery disease requiring cardiac and noncardiac surgery. Circulation. 2013;128: Hastings S, Myles P, McIlroy D. Aspirin and coronary artery surgery: a systematic review and meta-analysis. Br J Anaesth [Internet]. 2015;115: Available from: 2. Siller-Matula JM, Petre a., Delle-Karth G, Huber K, Ay C, Lordkipanidze M, et al. Impact of preoperative use of P2Y12 receptor inhibitors on clinical outcomes in cardiac and non-cardiac surgery: A systematic review and meta-analysis. Eur Hear J Acute Cardiovasc Care [Internet]. 2015; Available from: Cannon CP, Mehta SR, Aranki SF. Balancing the benefit and risk of oral antiplatelet agents in coronary artery bypass surgery. Ann Thorac Surg [Internet]. 2005;80: Available from: 3. Biancari F, Airaksinen KEJ, Lip GYH. Benefits and risks of using clopidogrel before coronary artery bypass surgery: Systematic review and meta-analysis of randomized trials and observational studies. J Thorac Cardiovasc Surg [Internet]. The American Association for Thoracic Surgery; 2012;143(3): e4. Available from: Dunning J, Versteegh M, Fabbri A, Pavie A, Kolh P, Lockowandt U, et al. Guideline on antiplatelet and anticoagulation management in cardiac surgery. Eur J Cardio-thoracic Surg. 2008;34: Mahla E, Metzler H, Tantry US, Gurbel P a. Controversies in oral antiplatelet therapy in patients undergoing aortocoronary bypass surgery. Ann Thorac Surg [Internet]. Elsevier Inc.; 2010;90(3): Available from: Miceli A, Duggan SMJ, Aresu G, de Siena PM, Romeo F, Glauber M, et al. Combined clopidogrel and aspirin treatment up to surgery increases the risk of postoperative myocardial infarction, blood loss and reoperation for bleeding in patients undergoing coronary artery bypass grafting. Eur J Cardiothorac Surg [Internet]. 2013;43(June 2012): Available from: 5. Reaume KT, Regal RE, Dorsch MP. Indications for dual antiplatelet therapy with aspirin and clopidogrel: Evidence-based recommendations for use. Ann Pharmacother. 2008;42: Gerstein NS, Schulman PM, Gerstein WH, Petersen TR, Tawil I. Should More Patients Continue Aspirin Therapy Perioperatively? Ann Surg. 2012;255(5): Cao C, Indraratna P, Ang SC, Manganas C, Park J, Bannon PG, et al. Should clopidogrel be discontinued before coronary artery bypass grafting for patients with acute coronary syndrome? A systematic review and meta-analysis. J Thorac Cardiovasc Surg [Internet]. Elsevier Inc.; 2014;148(6): Available from: 8. Fitchett D, Mazer CD, Eikelboom J, Verma S. Antiplatelet therapy and cardiac surgery: Review of recent evidence and clinical implications. Can J Cardiol [Internet]. Canadian Cardiovascular Society; 2013;29(9): Available from: 9. Ma X, Ma C, Yan Y, Qian Z, Zheng X. Safety and efficacy outcomes of preoperative aspirin in patients undergoing coronary artery bypass grafting: a systematic review and meta-analysis. J Cardiovasc Pharmacol Ther [Internet]. 2014;19(324): Available from: Vorobcsuk A, Aradi D, Farkasfalvi K, Horváth IG, Komócsi A. Outcomes of patients receiving clopidogrel prior to cardiac surgery. Int J Cardiol [Internet]. Elsevier Ireland Ltd; 2012;156(1): Available from: Bellemain-Appaix A, O Connor S a, Silvain J, Cucherat M, Beygui F, Barthélémy O, et al. Association of clopidogrel pretreatment with mortality, cardiovascular events, and major bleeding among patients undergoing percutaneous coronary intervention: a systematic review and meta-analysis. JAMA [Internet]. 2012;308(23): Available from: Fox K a a, Mehta SR, Peters R, Zhao F, Lakkis N, Gersh BJ, et al. Benefits and risks of the combination of clopidogrel and aspirin in patients undergoing surgical revascularization for non- STelevation acute coronary syndrome: The clopidogrel in unstable angina to prevent recurrent ischemic events (CURE) trial. Circulation. 2004;110: Kapetanakis EI, Medlam D a., Petro KR, Haile E, Hill PC, Dullum MKC, et al. Effect of clopidogrel premedication in off-pump cardiac surgery: Are we forfeiting the benefits of reduced hemorrhagic sequelae? Circulation. 2006;113: