The Department of Anesthesiology Grand Round Series Perioperative management of antiplatelet therapy in patients with coronary artery stents Esi Rhett, MD Davide Cattano, MD PhD March 19, 2009
Disclaimer • No financial interest • Patient verbal consent has been obtained • All patient’s information has been de-identified and the use of it is restricted to quality improvement of medical practice
Learning Objectives • Understand the value of preoperative cardiac evaluation and risk stratification and the clinical indication for antiplatelet therapy. • Basic knowledge of platelet function and coagulation. • How aspirin and clopidogrel work • Understand the current ACC/AHA and ASA guidelines on the use of thromboprophylaxis and coronary stents and the limitations. • How to (ideally) approach the patient on antiplatelet therapy • Introduction to the concept of resistance to antiplatelet medications • Future projects
Introduction • Heart disease continues to be the #1 cause of morbidity and mortality in the United States and western nations. • Acute coronary syndrome- conditions related to myocardial ischemia ranging from stable angina to Q-wave myocardial infarction. (1.6 million Americans: 700,000 unstable angina and 900,000 divided btwn STEMI and NSTEMI) • Percutaneous coronary intervention (balloon angioplasty and stent placement) offers patients improved quality of life by decreasing angina and risk for myocardial infarction and death.
Introduction • “A major concern after successful coronary artery stent placement is the potential for acute stent thrombosis, with subsequent myocardial infarction and death.” American Society of Anesthesiologists. “Practice Alert for the Perioperative Management of Patients with Coronary Stents.” Anesthesiology 2009; 110(1): 22-23.
Introduction • To prevent stent thrombosis, cardiologists recommend dual antiplatelet medications consisting of a combination of aspirin and a thienopyridine usually clopidogrel. • However, when these patients present for surgery, there is a fear that platelet dysfunction can cause surgical site bleeding.
Why are these patients on antiplatelet therapy anyway? • Percutaneous Coronary Intervention is inherently thrombogenic because it disturbs the artery walls. • Drug eluting stents slowly release medications to prevent reendotheliaztion of the artery wall, this leaves tissue factor exposed where the coagulation cascade and platelet aggregation can occur. • Surgery is thrombogenic because it causes tissue damage and inflammation.
The patient: • “Mr. Smyth,” 36 year old Caucasian man • Presented to the Anesthesia Clinic December 2008, repeat anterior cervical 6 and 7 decompression with fusion • MedHx: HTN, dyslipidemia, DM II for 3 years, cervical herniated disc, ACS in 2003, 2008 • In March 2003, when he was only 31 years old, he had an episode of unstable angina, angiogram revealed a >95% occlusion in the LAD and received a sirolimus drug eluting stent.
The patient cont: • PSx: March 2008, first anterior cervical 6-7 disc decompression with fusion, uneventful hospital course. • He reported had “another MI” 3/25/08 in Dallas. • Meds: clopidogrel, aspirin (last dose one week before clinic visit), ramipril, metoprolol, glucophage, atorvostatin, and hydrocodone-acetaminophen • Social: non smoker, occ ETOH
What other information do you need to determine the patient’s risk for surgery? • He is unable to give any family history of cardiac disease or premature cardiac death because he is adopted. • He tolerates some physical activity; he is able to do work around the house and climb stairs without any chest pain or shortness of breath. • Cath(5/08) LAD stent patent with multiple other vessel with disease but recommend medical management for now • ECHO: EF 60-65% • EKG: normal sinus rhythm, no evidence of ST changes or Q waves
What other information do you need to determine the patient’s risk for surgery? • Vital signs: T96.5, B/P 123/79, P78, 97% on RA • Laboratory data significant for elevated glucose of 196mg/dL, Hb 13.7, all other labs wnl.
Would you want to stop his clopidogrel and aspirin for this procedure again? • Plan A: stop both clopidogrel and ASA • Plan B: continue both clopidogrel and ASA • Plan C: Admit the patient for short term antiplatelet therapy • Plan D: cancel the surgery
American Society of Anesthesiologists. “Practice Alert for the Perioperative Management of Patients with Coronary Stents.” Anesthesiology 2009; 110(1): 22-23.2007 Science Advisory • Drug Eluting stents (DES)- delay non cardiac surgery with high risk bleeding for 12 months, thienopyridine and ASA for 12 months • Bare Metal Stents (BMS)- delay elective non-cardiac surgery a minimum of 1 month (4-6 weeks depending on type of BMS), ASA 4-6 weeks • (Angioplasty alone delay for 3 weeks)
Fleisher LA, et al. “ACC/AHA 2007 Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery: Executive Summary.” J Am Coll Cardiol 2007; 50(17): 1707-1732. • “In patients who have received drug-eluting coronary stents and who must undergo urgent surgical procedures that mandate the discontinuation of the thienopyridine therapy, it is reasonable to continue aspirin if at all possible and restart the thienopyridine as soon as possible.”
Vascular spasm Platelet plug (primary hemostasis) Blood coagulation (secondary hemostasis) Platelet Plug3 Stages 1.Adhesion 2. Release of platelet granules 3.Aggregation Hemostasis • Morgan and Mihkail, Hepatic Physiology and Anesthesia p783-785
Resistance to antiplatelet therapy • Resistance and differences in response to antiplatelet medication has been known and investigated in recent years. • Clopidogrel is a prodrug that must be converted to the active form by cytochrome-p450 enzymes
Clopidogrel Nonresponsiveness Correlation with CYP3A4 Enzyme Activity 5.0 4.0 3.0 2.0 1.0 0 Nonresponders (25%) 100 80 9 Responders (75%) 2.7 1.0 80 37 20 1.9 0.7 60 Aggregation (%) 14CO2 exhaled/h (%) 40 20 0 Platelet aggregation 4 hours post clopidogrel* CYP3A4** activity *450 mg PO (P=0.0002); **P=0.15 Lau WC et al. J Am CollCardiol. 2003;41:225A.
Major questions • How do we test antiplatelet therapy response? • When (If) to stop antiplatelet therapy? • When to restart? • How much to restart: maintenance dose v loading dose? • What happens after 2 and 12months?
Platelet Function Monitoring • Clinical tests: Bleeding time , Platelet Funcion Assay-100, platelet aggregometry and the TEG • Thromboelastogram: advantage of being able to monitor ASA and thienopyridines and other GPIIb/IIIa inhibitors Gurbel PA, Becker RC, et al. “Platelet Function Monitoring in Patients with Coronary Artery Disease.” J Am Coll Cardiol 2007; 50(19): 1822-1834. Review.
What happened to Mr. Smyth? • Surgeons will not like idea of continuing antiplatelet medications. • When the surgeon was asked to consider maintaining at least the ASA, he refused. He did accepted restarting ASA the same day post op and the clopidogrel 48 hrs later.
What happened to Mr. Smyth? • Surgery proceeded without incident and he was discharged after a uneventful hospital course. • He was given aspirin 81mg chewable in house. • It is unknown when (or if) he restarted the clopidogrel. • Follow-up phone call showed a disconnected number…
Drug Eluting stents: Delay surgery for 12 months if possible to complete therapy Continue ASA and restart clopidogrel ASAP Bare Metal Stents: Delay for 2 months Continue ASA and restart clopidogrel ASAP Conclusions Memorial Hermann Hospital: UT system proposal
Perioperative management of antiplatelet agents in noncardiac surgery. Eur J Anaesthesiol. 2009 Mar;26(3):181-7. Links • Llau JV, Lopez-Forte C, Sapena L, Ferrandis R. • Department of Anaesthesiology and Critical Care Medicine, University Clinic Hospital, Valencia, Spain.
Up and coming research… • Dr. Ali Denktas and Dr. Evan Pivalizza • Safety Implications of Patients receiving Preoperative Antiplatelet therapy with Clopidgrel and/or Aspirin:Investigation of Thrombelastograph Platelet Mapping to objectively assess Platelet Inhibition and subsequent use to guide individual patient management. PI Evan Pivalizza, CO-PI Davide Cattano. • Perioperative management of antiplatelet therapy (Clopidogrel); retrospective chart review. PI Ali Denktas, CO-PI Davide Cattano.