perioperative antiplatelet therapy

1. PERIOPERATIVE ANTIPLATELET THERAPY SHOUTEH CHANG COLLEGE OF MEDICINE, NATIONAL TAIWAN UNIVERSITY Sep. 24 th, 2007

3. Antiplatelet agents - Aspirin

4. Antiplatelet agents - Aspirin Low Dose Aspirin: inhibits platelet cyclooxygenase to reduce the level of TXA2 compared to PGI2

5. Antiplatelet agents - Aspirin

6. Antiplatelet agents - Clopidogrel Inhibit the ADP pathway of platelets Irreversible block the ADP receptor on platelets Reduce platelet aggregation Duration: 7-10 days

7. Antiplatelet agents - Clopidogrel Decrease the risk of MI in unstable angina Coronary stent thrombosis Recurrent stroke Increase the risk of spontaneous hemorrhage Indications: Non-responders and allergic to aspririn Dual antiplatelet therapy Unstable coronary plaque Re-endothelialization phase of coronary stents

8. Antiplatelet agents – GP IIb/IIIa antoagonists Inhibit the common final process of platelet aggregation Abciximab, Eptifibatide, Tirofiban Prevention of immediate thrombosis of coronary stents Effective platelet aggregability restored in 48hrs

9. Antiplatelet agents – Statins HMG-CoA reductase Reduce LDL Increased stability of atherosclerotic lesions Anti-inflammation Increase NO production Decrease vascular smooth muscle proliferation Diminish platelet aggregation and re-stenosis rate after PCI

10. Antiplatelet agents – Statins Methods: 100 patients 20 mg/day atorvastatin or placebo for 45 ds, randomized, double-blind Irrespective of [cholesterol] Vascular surg. ave. 30 ds Prospective f/p 6 mths The CV events: death from cardiac cause, nonfatal MI, UA, and stroke.

11. Percutaneous coronary revascularization 2658 pts PCI Randomized Placebo+Aspirin, Clopidogrel+Aspirin 31% reduction of cardiovascular mortality or MI rate in Clopidogrel group

12. Percutaneous coronary revascularization The optimal timing for elective noncardiac surgery (NCS) after coronary stenting :uncertain 27 pts: NCS within 3 weeks of coronary stenting 6/7 in whom thienopyridine discontinued: died of stent thrombosis 1/20, thienopyridine continued: died The frequency of perioperative hemorrhage :similar whether or not the antiplatelet agent was continued. 20 pts: NCS more than 3 weeks following stenting Only 1 perioperative died

13. Percutaneous coronary revascularization Types: BMS: Bare metal stents DES: Drug-eluting stents Revascularization: Based on Pathology DES: dual therapy for 1 yr Aspirin: a life long treatment for both

14. Postoperative myocardial infarction

15. Withdrawal of antiplatelet agents Withdrawal 7-10 ds before a surgical procedure? Rebound effect on stopping antiplatelet agents: Pro-thrombotic effects Excessive thromboxane A2 and decreased fibrinolysis Secondary prevention for CAD Cardiac complication rate (X3) Risk higher with coronary stents (X15) More dangerous in the perioperative period

16. Withdrawal of antiplatelet agents – Stent thrombosis Predictors: Major: Stopping antiplatelet agents Others: stenting of small vessels, multiple lesions, long stents, bifurcation lesions, suboptimal stent result, low ejection fraction, advanced age, renal failure, DM Long term dual antiplatelet therapy High mortality rates Abrupt interruption of a high-output vessel DES: inhibit collateral growth

17. Hemorrhagic risks On Aspirin Surgical bleeding ? 2.5-20% No increase in surgical mortality or morbidity Post-op intracerebral hematoma ?in neurosurgery On dual therapy S urgical bleeding ? 30% No increase in surgical mortality or morbidity Except intracranial surgery

18. Possible approaches

19. Possible approaches Aspirin For secondary prevention Lifelong, never be stopped before surgery For primary prevention Safely withdrawn, no more than 7 days before surgery Clopidogrel Stop in high surgical hemorrhagic risk Stop in low CV risk

20. Possible approaches

21. Possible approaches – platelet transfusion Hemostatis: 50% normal function platelets On Clopidegral New platelets may be inhibited by drug in the circulation Clopidegral half life:4hr On abciximab Platelet function returns in 48hrs On Tirofiban and eptifibatid Platelet function returns in 2hrs

22. Possible approaches – possible substitutes Heparin Efficient in unstable angina, NSTEMI NSAID Ibuprofen, indobufen Reversible, completely recovered within 24 hrs GP-IIb/IIIa inhibitor Shortacting

23. Postoperative PCI Treatment of CAD be restarted ASAP post OP Routine monitor cardiac enzyme: silent ischemia ST elevation: PCI and coronary angiography Dilatation Stenting: problematic due to hypercoagulability and post-op acute systemic inflammatory syndrome Impossible to use thrombolysis, GP IIb/IIIa in the first 24-48 hrs

24. Take Home Message Risk of coronary thrombosis after antiplatelet drugs withdrawal>>Surgical bleeding if continued In secondary prevention, aspirin is a lifelong therapy and should never be stopped Clopidogrel: until the coronary stents are fully endothelialized 3 mths for BMS 1 yr for DES

25. Reference [1]. Perioperative antiplatelet therapy: the case for continujing therapy in patients at risk of myocardial infarction, Br. J. Anaesth. 99(3): 316-28(2007) [2]. Basic and Clinical Pharmacology, 9th edition, 554-555, 568-569, 578-582 [3]. www.gravitywaves.com/chemistry/CHE452 [4]. Am J Health-Syst Pharm, 2002 [5]. Perioperative myocardial infarction—aetiology and prevention, Br. J. Anaesth. 2005 95: 3-19 [6]. Perioperative myocardial injury: individual and population implications, Br. J. Anaesth. 2004 93: 3-8 [7]. http://www.clevelandclinic.org/heartcenter/pub/news/hot/crp2.htm [8]. Reduction in cardiovascular events after vascular surgery with atorvastatin ,J. of Vasc. Surg. pp. 967-975 [9]. Major Noncardiac Surgery Following Coronary Stenting, Catheter Cardiovasc Interv 2004;63:141–145.

26. Thank You For Your Attention