ANESTHESIA FOR NON CARDIAC SURGERY IN PATIENTS WITH CORONARY STENTS

1. Dr. Mahesh Vakamudi Professor and Head Department of Anesthesiology, Critical Care and Pain Medicine (ISO 9001:2008 CERTIFIED) Sri Ramachandra University Chennai ANESTHESIA FOR NON CARDIAC SURGERY IN PATIENTS WITH CORONARY STENTS

2. Magnitude of the problem • 2 million patients undergo PCI annually • 90% of these patients receive one or more intracoronary stents • 5% of these patients will undergo non cardiac surgery in the first year after stenting

3. NUMBER Percutaneous coronary interventions > Coronary artery bypass surgeries Increase procedural success Stents commonly placed Decrease restenosis

4. Why this lecture? • In patients who have coronary stents, perioperative coronary stent thrombosis is a catastrophic complication • Non cardiac surgery, especially if surgery is performed immediately after stenting and particularly if dual antiplatelet therapy is discontinued – increases this risk • Maintain balance between risk of bleeding and stent thrombosis is our dilemma. • What do we do? That’s what this lecture is about

5. Which patients are prone for stent thrombosis? • Patients with a suboptimal angiographic result • Those with high risk lesions • Small vessels • Bifurcation lesions • Those with diabetes and renal failure • Those whose dual antiplatelet therapy has been stopped

6. Scoring system for LST Risk score for prediction of LST Low Medium High Very High 0 6 9 13 19

7. Why thrombosis? Early surgery STENT THROMBOSIS

8. Discontinuation of Aspirin and Clopidogrel Loss of anti-inflammatory protection by clopidogrel Rebound increase in COX 1 and TXB2 Loss of antiplatelet effect Increased thrombin and decreased fibrinolysis Stent thrombosis ⁺ & Surgery Prothrombotic state MI

9. Coronary angioplasty without stents Abrupt vessel collapse due to acute recoil and vasospasm Stent placement injures vessel wall and causes scar tissue growth inside the stent Stent restenosis Bare metal stents Prevent neointimal hyperplasia Delay endothelialization Drug eluting stents but Antiproliferative and immunosuppressive properties Late stent thrombosis Platform + Carrier (Stent + Drug)

10. Incidence of deaths Bare metal stents 8 out of 25 patients who underwent surgery within 2 weeks died – 7 of MI, 1 of bleeding None out of 15 patients who underwent surgery after 15 days died Kaluza GL, Joseph J, Lee JR, Raizner ME, Raizner AE. Catastrophic outcomes of noncardiac surgery soon after coronary stenting. J Am CollCardiol 2000;35:1288 –94.

11. Bare metal stents The risk of death, MI, or stent thrombosis was elevated for 6 weeks, not for just 2 weeks Of 27 patients who underwent non cardiac surgery within 3 weeks of BMS, 86% of those who stopped antiplatelets died Sharma AK, Ajani AE, Hamwi SM, et al. Major noncardiac surgery following coronary stenting: when is it safe to operate? Catheter CardiovascInterv 2004;63:141–5. Wilson SH, Fasseas P, Orford JL, et al. Clinical outcome of patients undergoing noncardiac surgery in the two months following coronary stenting. J Am CollCardiol 2003;42:234–40.

12. DES • First generation DES elute • Sirolimus • Paclitaxel • Second generation DES elute • Zotarolimus • Everolimus

13. Drug eluting stents McFadden et al. (19) reported DES thrombosis in 3 patients undergoing surgery late (343 to 442 days) after implantation. Nasser et al. (20) reported sirolimus-eluting stent (SES) thrombosis in 2 patients after surgery performed 4 and 21 months after SES implantation.

14. Avoid preoperative coronary stenting Avoid preoperative coronary revascularization, unless there exists a strong and proven indication Choose BMS if Surgery needed from 6 weeks to 12 months Bleeding diathesis Patient unable or unwilling to receive long term clopidogrel • Stent selection (BMS vs DES) Consider balloon angioplasty if surgery is needed within 6 weeks. Avoid stents • Delay surgery Choose DES if surgery is needed after 12 months BMS – 6 weeks DES – 12 months • Optimize antiplatelet therapy Continue antiplatelet therapy during surgery • Education and collaboration Surgeons anesthesiologists cardiologists

15. Avoiding revascularization • CARP trial • 510 stable patients with CAD undergoing major vascular surgery • Randomized to revascularization (by CABG or PCI) or no revascularization • Similar incidence of postoperative MI and 27 month survival in both the groups So, first ask the question: Is revascularization necessary?

16. Revascularization without stents (Balloon only) • Patients with acute coronary syndrome and those with profound ischemia on non invasive testing do need revascularization • Can be done without stents: Percutaneous balloon angioplasty • In this study, when surgery was done 11 days after PCI, only 1 patient died and 1 had an AMI Gottlieb A, Banoub M, Sprung J, Levy PJ, Beven M, Mascha EJ. Perioperative cardiovascular morbidity in patients with coronary artery disease undergoing vascular surgery after percutaneoustransluminal coronary angioplasty. J CardiothoracVascAnesth 1998;12:501– 6.

17. When surgery after Balloon angioplasty? • 2002 ACC AHA guidelines • Delaying noncardiac surgery for 6 to 8 weeks was discouraged because restenosis could have occurred • Performing noncardiac surgery too early after the PCI also may be risky because acute or subacute closure after balloon angioplasty usually occurs within hours to days after the procedure. • Delay surgery for 1 week after balloon angioplasty

18. If stenting can’t be avoided • Complex lesion or inability to achieve optimal result with balloon angioplasty • Choose the right stent • Surgery needed with 12 months: Choose BMS • Surgery can be delayed for > 12 mth: DES • BMS endothelialize more rapidly than DES • Sirolimus eluting stent preferable as it requires 3 mths of antiplatelet therapy than a paclitaxel eluting stent that requires 6 mths of clopidogrel

19. Delay surgery • 6 weeks BMS • 12 months DES

20. Major adverse cardiac events (%) Bare metal stents 10 Drug eluting stents 8 6 4 2 0 0 2 4 6 8 10 12 14 16 18 Time from stent until surgery (months)

22. What are the steps to prevent stent thrombosis in these patients coming for non cardiac surgery?

23. Periopantiplatelet therapy • Continue dual antiplateletthearpy during and after surgery • Discontinue clopidogrel but “bridge” the patient to surgery with Glycoprotein IIb/IIIa inhibitor or an antithrombin, and restart clopidogrel as soon as possible after surgery • Discontinue clopidogrel before surgery and restart it as soon as possible after surgery

24. Impact of aspirin on bleeding • Most studies in cardiac and vascular surgery • Safe in doses of 75 – 150 mg • Increases bleeding by a factor of 1.5, no effect on morbidity and mortality • Avoid in TURP and intracranial surgery (as bleeding in these situations can be life threatening) Continue aspirin monotherapy in elective non cardiac surgery

25. Option 1 : Continue therapy • Dental extractions • Cataract surgery • Dermatologic surgery

26. Option 2: Bridging therapy • Bridge using short acting antiplatelet or an anticoagulant • Platelet inhibitors are the more logical choice as stent thrombosis is a platelet mediated phenomenon • Cessation of heparin in a patient not on antiplatelets can cause rebound effect and stent thrombosis

27. Bridging therapy • A shortacting GP IIb/IIIa inhibitor (tirofiban or eptifibatide) or thrombin inhibitor, or both, is substituted for clopidogrel during the perioperative period • Role • Prevent platelet aggregation • Displace fibrinogen from GP IIb/IIIa receptors • Block signaling processes

28. Bridging therapy • Tirofiban and eptifibatide are administered parenterally • Have half-lives 2 h • Eliminated by renal clearance. • Infusion rate is reduced by half in patients with reduced renal function • Platelet function returns to 60%–90% of normal after the infusion is stopped for 6–8 h.

29. When bridging therapy? • Surgeries with high risk of bleeding • Intracranial • Spinal • Retinal

30. Other drugs • Reversible P2Y12 receptor antagonists are undergoing clinical trials • Cangrelor is a parenteral, reversible direct P2Y12 inhibitor • Half-life of 5–9 min allows 100% recovery of platelet function 1 h after the infusion is discontinued • 4 mcg/kg/min infusion achieves complete platelet inhibition when measured at 4 min • AZD6140 is an oral, reversible direct P2Y12 receptor antagonist with a half life of 12 hrs.

31. Problems with bridging therapy • Expensive • Logistically difficult • Exposes patients to risks associated with a prolonged hospitalization • Some claim that it confers no protection against intraoperative stent thrombosis

32. Option 3: Stop antiplatelets • Neurosurgery • Restart clopidogrel after surgery • 600 mg loading dose – Maximal inhibition of platelet aggregation in 2 – 4 hours (takes 6 hrs with 300 mg) • Reduces the incidence of hyporesponsiveness to platelets (which are activated due to surgery)

33. Anesthetic drugs metabolized by CYP3A4 like midazolam can irreversibly inhibit this enzyme which metabolizes clopidogrel into its active form, modulating its antiplatelet effect

34. Steps: Preoperative evaluation • Determine the type of stent: BES, SES, PES • When were stents implanted? • Determine location of stent in coronary circulation • How complicated was the revascularization? • Is there a previous history of stent thrombosis? • What antiplatelet regimen is being followed? • Determine co-morbidities? • What is the recommended duration of antiplatelet therapy for this patient? • Co-ordinate with cardiologist

35. Steps • Perform procedure in centers where there is 24 hr interventional cardiology coverage for emergency PCI

36. Intraop management • Tight hemodynamic control • Use of beta blockers • Good HR control • Good BP control • Decrease sympathetic outflow and therefore decrease platelet activation

37. Regional anesthesia in patients on antiplatelets • Advantages • Attenuation of hypercoagulable state • Systemically absorbed LA have antiplatelet effect • Follow ASRA guidelines • For patients receiving bridging therapy with eptifibatide or tirofiban, 8 h must elapse before a neuraxial blockade can be performed

38. Management of stent thrombosis • ST segment elevation acute myocardial infarction • Reperfusion • Thrombolytic therapy less effective than primary PCI • Platelet mediated phenomenon • Risk of bleeding • All that is required during PCI is aspirin and one dose of heparin or bivalirudin

39. Role of platelet transfusion • Transfused platelets are not inhibited by serum therapeutic levels of antiplatelets • The thrombogenic surface of stents may attract and activate donor platelets to an even greater extent than endogenous platelets Platelet transfusions to be avoided except in instances of life threatening bleeding

40. Algorithm for patients with DES for NCS Emergency Semi emergency Elective Assess risk of bleeding DES > 1 yr DES < 1 yr Low Intermediate High STOP Length of DAPT Stop Anti PLT Continue DAPT > 1 yr < 1 yr Assess risk of thrombosis Stop clopidogrel Continue LD aspirin Low High Proceed with surgery Hosp Admn ? IV Anti PLT

41. Education • In a survey of anesthesiologists, 63% were not aware of recommendations about the appropriate length of time between stent placement and a subsequent surgical procedure, and one-third recommended no delay or a delay of only 1 to 2 weeks, which is insufficient for BMS, and even more so for DES Patterson L, Hunter D, Mann A. Appropriate waiting time for noncardiac surgery following coronary stent insertion: views of Canadian anesthesiologists. Can J Anaesth 2005;52:440 –1

42. Take home points • Many patients come for non cardiac surgery after PCI • Stent thrombosis is a catastrophe • Remember the stepwise approach to the issue

43. Avoid preoperative coronary stenting • Stent selection (BMS vs DES) Thank you • Delay surgery • Optimize antiplatelet therapy • Education and collaboration