1. CARE OF NSTEMI PATIENTS LATEST GUIDELINES Rick Barney MD FACEP Emergency Medicine Beloit Memorial and University of Wisconsin

2. New NSTEMI Guidelines by ACC/AHA Released August 6th 2007 www.americanheart.org

3. NSTEMI Protocols not followed well STEMI- straight forward and well followed NSTEMI- no hospital agreement, under use of available treatment, no agreement even amongst cardiologists

4. Following ACC/AHA Guidelines Significantly Reduces Risk of Mortality Bhatt DL, et al. JAMA. 2004;292(17):2096-2104. Incidence of in-hospital mortality was lower with adherence to ACC/AHA Guidelines 32.4%↓ (P < 0.001)

5. NSTEMI- Definition Coronary symptoms with ST segment depression, or T wave inversions (new) and/or elevated biomarkers (Troponin preferred)

6. Nitro Recommendation If new angina pattern, call 911 if one single nitro has not helped. Take 2nd and 3rd dose while waiting for EMS arrival If typical stable angina pattern, still recommend call for help if three nitro doses 5 minutes apart does not help.

7. Aspirin and Pre-Hospital 12 lead ECG Aspirin should be given immediately to all patients who may have a coronary Syndrome. Only reason to not give is a true allergy. Strong recommendation for pre-hospital 12 lead analysis

8. Positive Biomarkers are critical to ED Care Latest studies show patients with positive Troponins do best with early invasive management, Clopidogrel, anticoagulation, and glycoprotien II b III a inhibition.

9. USE OF BETA BLOCKERS COMMIT Trial shows some risk in using IV Metoprolol. For NSTEMI-use IV if hyperdynamic, otherwise PO within 24 hours of arrival

10. Morphine results in higher mortality for NSTEMI patients Due to blocking pain, yet ischemia still present Due to hypotension Due to decreased myocardial perfusion Many now use Fentanyl instead

11. Early Invasive Management Improves Outcomes NSTEMI- thus high risk patients in general do better if treated aggressively in ED, then to cath lab in 4-24 hours. 18% death or MI reduction. Even studies on stabilization and later treatment are predicated on aggressive ED treatment In general, this includes Clopidogrel, anticoagulant, and Glycoprotein II B III A Inhibition

12. 2007 Anti-platelet Guidelines Nothing new on Aspirin- continue to use Recommend Clopidogrel or II B III A OR Use both Clopidogrel and II B III A Using both makes more scientific sense as drugs work differently. Some patients are partial or non-responders to Clopidogrel.

13. Anti-Platelet Therapy Clopidogrel is irreversible. Will delay CABG 3-5 days. Integrelin is reversible once infusion is shut off. Anti-platelet therapy is critical to success and is under- utilized Coordinated, standard approach at your institution is desirable. ISAR-REACT 2 study shows adding Glycoprotein IIBIIIA

14. The Central Role of the Platelet in NSTE ACS

15. Thrombin Fibrin Mesh Fibrinogen cross links to form platelet-rich thrombus Activation of GP IIb-IIIa TxA 2 ADP AT III* Factor Xa LMWH Thrombolytics ASA Clopidogrel Platelet Activation Agonist degranulation Prothrombin Platelet recruitment and aggregation Formation of mature thrombus Plasma clotting cascade Intrinsic Pathway Bivalirudin UFH *AT III = antithrombin III. Stein B, et al. J Am Coll Cardiol. 1989;14(4):813-836; DeJong MJ, et al. Crit Care Nurs Clin N Am. 1999;11(3):355- 371; White HD. Am J Cardiol. 1997;80(4A):2B-10B. Sites of Antithrombotic Drug Action Coagulation cascade Platelet cascade GP IIb-IIIa inhibitors Other agonists

16. Results from cross-linking of platelets by fibrinogen at platelet receptors GP IIb-IIIa at site of plaque rupture Platelet Fibrinogen Ruptured plaque GP IIb-IIIa NSTE ACS is generally caused by partially occlusive, platelet-rich thrombus in a coronary artery Unobstructed lumen Thrombus Artery wall Van de Werf F. Thromb Haemost. 1997;78(1):210-213; Moser M, et al. J Cardiovasc Pharmacol. 2003;41(4): 586-592; Reprinted with permission from Davies MJ. Heart. 2000;83(3):361-366. © BMJ Publishing Group Ltd. 2005. The Role of the Platelet in Non-ST-segment Elevation Acute Coronary Syndrome (NSTE ACS)

17. The Thrombus in STEMI Results from stabilization by fibrin mesh of a platelet aggregate at site of plaque rupture platelet RBC* fibrin mesh STEMI is generally caused by a completely occlusive fibrin-rich thrombus in a coronary artery *RBC = red blood cell. GP IIb-IIIa inhibitors are not indicated for STEMI. Van de Werf F. Thromb Haemost. 1997;78(1):210-213; White HD. Am J Cardiol. 1997;80(4A):2B-10B; Davies MJ. Heart. 2000;83(3):361-366.

18. Microembolization in Unstable Angina Courtesy of C. Michael Gibson, MS, MD, Director TIMI Data Coordinating Center, Brigham & Women’s Hospital, Associate Chief of Cardiology, Interventional Cardiologist, Beth Israel Deaconess Medical Center, Harvard Medical School.

19. Variable Clopidogrel Response At 5 Days UA Patients* (n = 32) At 4 Hours Healthy Volunteers † (n = 25) Responders 47% Responders 72% Low responders 32% Nonresponders 16% Nonresponders 22% Low responders 12% *Received an oral loading dose of 300 mg of clopidogrel followed by 75 mg daily; † Received a 450-mg loading dose of clopidogrel. The use of clopidogrel in this study was not consistent with applicable FDA-approved Prescribing Information. Gurbel PA, et al. Circulation. 2003;107(23):2908-2913; Lau WC, et al. Circulation. 2004;109(2):166-171. Response measured after elective coronary artery stent implantation

20. GP IIb-IIIa Inhibitors Are an ACC/AHA Guidelines IA Recommendation Braunwald E, et al. J Am Coll Cardiol. 2002;40(7):1366-1374. CAUTIONARY INFORMATION  No clopidogrel within 5-7 days prior to CABG surgery  No enoxaparin within 24 hours prior to CABG surgery  No abciximab, if PCI is not planned RECOMMENDED TREATMENT REGIMEN  Aspirin (IA); clopidogrel if aspirin is contraindicated (IA)  LMWH or UFH (IA)  GP IIb-IIIa inhibitor (IA)  Beta blocker (IB)  Nitrates (IC) PCI or CABG SURGERY IF CORONARY ANATOMY IS SUITABLE (IA) SEND FOR CATHETERIZATION & REVASCULARIZATION WITHIN 24-48 HOURS AT PRESENTAION HIGH-RISK FEATURES  Signs of ischemia at rest > 20 minutes AND ST-segment depression and/or elevated cardiac biomarkers LEVELS OF EVIDENCELEVELS OF EVIDENCE RANK I.Evidence and/or agreement that treatment is effectiveA. Based on large, randomized trials IIa.Weight of evidence favors useB. Based on smaller trials or careful analyses IIb.Usefulness less well establishedC. Based on expert consensus III.Evidence and/or agreement that treatment is not effective

21. Changes in Cardiac Arrest Management

22. Pharmacology No improvements evident based on science with drugs to improve outcome Epinephrine every 5 minutes No added benefit to Vasopressin Amiodarone and Lidocaine equal effectiveness

23. Defibrillation Primary treatment for V-fib at 3 minutes and under Should be delayed until good CPR for 2 minutes if down time over 3 minutes Biphasic should be used AED’s good in 3 minutes, bad after One shock only with no pulse checks after

24. Vascular Access Avoid ET drugs whenever possible Peripheral IV’s OK Central IV’s slightly better, but compression interruption frequent with placement Interosseous recommended when peripheral IV’s not obtainable

25. Pathophysiology of V-Fib Arrest

30. How Compressions move blood

34. What about AED’s? Great in first 3 minutes. Must be in community. Deadly after this as delay to shock is over 30 seconds. Manual defib required after 3 minutes.

35. Defibrillation No more stacked shocks Takes too long All shocks maximum energy. EMS probably should not use AED’s Biphasic increases efficacy

36. Pulse Checks Deadly!! Only check pulses when rhythm appears to have converted thru CPR on ECG or signs of life ECC says check before shock delivered after 5 cycles of 30:2 CPR

37. What about intubation? In first 6 minutes, not a priority (V-fib) ASAP in PEA and Asystole. Understand that positive pressure breaths decrease cardiac output. Some air exchange from CPR plus gasping. Once intubated, 1 second breaths,six per minute. NO MORE.

38. Airway Combitube or ET equivalent RSA Mentality-view and see cords place ET, otherwise immediate Combitube first try.

39. Protocol Dispatch instructs CCC If good CPR on EMS arrival, shock max X1 If no or poor CPR, immediate compressions

40. Protocol OP airway Non-rebreather face mask @ 90+% 200 compressions IV access Epinephrine 1mg IVP Vasopressin 40 units IVP ASAP One shock, 3-5 seconds, no pulse checks.

41. Protocol Begin second round of 200 compressions Amiodarone 300mg IVP Shock X1 at max joules No pulse checks, not off chest more than 5 seconds.

42. Protocol Begin 3rd round of compressions Epinephrine 1mg IVP Shock X1 after 200 compressions

43. Protocol During 4th round of compressions place definitive airway without halting compressions on first attempt.

44. Protocol 200 compressions alternating epinephrine with antidysrhythmic drug and shock X1. Remain on scene and work until pulse or non- shockable rhythm.

45. 48% Neuro-intact survivors!! 10% before new protocol

46. QUESTIONS??