Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

Non-ST-Segment Elevation Acute Coronary Syndrome (NSTE-ACS ...

4,587 views

Published on

Non-ST-Segment Elevation Acute Coronary Syndrome (NSTE-ACS ...

  1. 1. <ul><li>Non-ST-Segment Elevation Acute Coronary Syndrome (NSTE-ACS) </li></ul>From the Committee on Post-Graduate Education, Council on Clinical Cardiology, American Heart Association Date Posted: July, 2004.
  2. 2. Non-ST-Segment Elevation Acute Coronary Syndrome (NSTE-ACS) Pathophysiology, Epidemiology, Risk Stratification, Evaluation, and Management Slides compiled and annotated by Glenn N. Levine, MD, with thanks to many, particularly Christopher P. Cannon, MD. The content of these slides is current as of July 2004 Future revisions will be posted on the American Heart Association website (www.americanheart.org)
  3. 3. Non-ST-Segment Elevation Acute Coronary Syndrome <ul><li>Pathology, Pathophysiology, and Epidemiology </li></ul><ul><li>Risk and Risk Stratification </li></ul><ul><li>Initial Therapies and Management </li></ul><ul><li>Platelets and Anti-Platelet Therapies </li></ul><ul><li>Anti-Thrombin Studies and Recommendations </li></ul><ul><li>Early Invasive Strategy </li></ul><ul><li>Peri- and Post-Discharge Medications and Management </li></ul>
  4. 4. Pathology, Pathophysiology, and Epidemiology
  5. 5. The Vulnerable Plaque Reproduced with permission from Falk E, et al. Circulation. 1998;92:657-671. Large Lipid Core Thin, Vulnerable, Fibrous Cap
  6. 6. Ruptured Plaque with Occlusive Thrombus Formation Reproduced with permission from Falk E, et al. Circulation. 1998;92:657-671. Thrombus Formation
  7. 7. Atherothrombosis: Thrombus Superimposed on Atherosclerotic Plaque Adapted with permission from Falk E, et al. Circulation. 1998;92:657-671. Slide reproduced with permission from Cannon CP. Atherothrombosis slide compendium. Available at: www.theheart.org.
  8. 8. Characteristics of Unstable and Stable Plaque Thin fibrous cap Inflammatory cells Few SMCs Eroded endothelium Activated macrophages Thick fibrous cap Lack of inflammatory cells Foam cells Intact endothelium More SMCs Adapted with permission from Libby P. Circulation . 1995;91:2844-2850. Slide reproduced with permission from Cannon CP. Atherothrombosis slide compendium. Available at: www.theheart.org. Unstable Stable
  9. 9. The Stable and Unstable Plaque Reproduced with permission from Yeghiazarians Y, Braunstein JB, Askari A, et al. Unstable angina pectoris. N Engl J Med. 2000;342:101-114.Copyright © 2000, Massachusetts Medical Society. All rights reserved.
  10. 10. ACS Pathophysiology Plaque Rupture, Thrombosis, and Microembolization Quiescent plaque Platelet-thrombin micro-emboli Plaque rupture Process Plaque formation Inflammation Multiple factors ? Infection Plaque Rupture ? Macrophages Metalloproteinases Thrombosis Platelet Activation Thrombin Marker Cholesterol LDL C-Reactive Protein Adhesion Molecules Interleukin 6, TNF  sCD-40 ligand MDA Modified LDL D-dimer, Complement, Fibrinogen, Troponin, CRP, CD40L Vulnerable plaque Macrophages Foam Cells Collagen  platelet activation TF  Clotting Cascade Lipid core Metalloproteinases Inflammation Courtesy of David Kandzari.
  11. 11. Systemic and Focal Plaque Rupture by IVUS in ACS Patients Undergoing PCI Adapted from Rioufol G, et al. Circulation. 2002;106:804-808. Slide courtesy of David Kandzari. Plaque rupture at site of culprit lesion Plaque rupture elsewhere than site of culprit lesion Plaque rupture in different artery than culprit lesion % % % Analysis of 72 Arteries (n=24 TnI-positive ACS Patients) % Plaque rupture 37.5 79.0 70.8 0 25 50 75 100
  12. 12. Frequency of multiple active plaque ruptures beyond the culprit lesion. Patients (%) 80% of Patients With  2 Plaques 0 5 10 15 20 25 30 0 1 2 3 4 5 N=24 Frequency of Multiple “Active” Plaques in Patients With ACS ACS indicates acute coronary syndrome. Adapted from Rioufol G, et al. Circulation. 2002;106:804-808. Slide reproduced with permission from Cannon CP. Atherothrombosis slide compendium. Available at: www.theheart.org.
  13. 13. Thrombus Formation and ACS UA NQMI STE-MI Plaque Disruption/Fissure/Erosion Thrombus Formation Non-ST-Segment Elevation Acute Coronary Syndrome (ACS) ST-Segment Elevation Acute Coronary Syndrome (ACS) Old Terminology: New Terminology:
  14. 14. Atherothrombosis* is the Leading Cause of Death Worldwide 1 *Atherothrombosis defined as ischemic heart disease and cerebrovascular disease. 1 The World Health Report 2001 . Geneva: WHO; 2001. Reprod.with permission from Cannon CP. Atherothrombosis slide compendium. Available at: www.theheart.org. 22.3 19.3 12.6 9.7 9 6.3 0 5 10 15 20 25 30 Atherothrombosis* Infectious Disease Cancer Injuries Pulmonary Disease AIDS Causes of Mortality (%)
  15. 15. 3.2 Million Hospital Admissions Coronary Atherosclerosis Acute Myocardial Infarction 1,153,000 Admissions 829,000 Admissions Hospitalizations in the US Due to Atherosclerotic Disease Cerebrovascular Disease 961,000 Admissions Vascular Disease Other Ischemic Heart Disease 280,000 Admissions From Popovic JR, Hall MJ. Advance Data . 2001;319:1-20. Slide reproduced with permission from Cannon CP. Atherothrombosis slide compendium. Available at: www.theheart.org.
  16. 16. * Based on data from the ARIC study of the National Heart, Lung, and Blood Institute, 1987-1994. Includes Americans hospitalized with definite or probable MI or fatal CHD, not including silent MIs. ACS indicates acute coronary syndrome; MI, myocardial infarction; ARIC, Atherosclerotic Risk in Communities; and CHD, coronary heart disease. From American Heart Association . Heart Disease and Stroke Statistics—2003 Update. Epidemiology of ACS in the United States <ul><li>Single largest cause of death </li></ul><ul><ul><li>515,204 US deaths in 2000 </li></ul></ul><ul><ul><li>1 in every 5 US deaths </li></ul></ul><ul><li>Incidence </li></ul><ul><ul><li>1,100,000 Americans will have a new or recurrent coronary attack each year and about 45% will die* </li></ul></ul><ul><ul><li>550,000 new cases of angina per year </li></ul></ul><ul><li>Prevalence </li></ul><ul><ul><li>12,900,000 with a history of MI, angina, or both </li></ul></ul>Slide reproduced with permission from Cannon CP. Atherothrombosis slide compendium. Available at: www.theheart.org.
  17. 17. Risk and Risk Stratification
  18. 18. GUSTO IIb: Correlation of 6-Month Mortality With Baseline ECG Findings in Patients With ACS GUSTO indicates Global Use of Strategies To Open Occluded Arteries in Acute Coronary Syndromes; ECG, electrocardiogram; ACS, acute coronary syndrome; and STEMI, ST-segment elevation myocardial infarction. Figure adapted with permission from Savonitto S, Ardissino D, Granger CB, et al. Prognostic value of the admission electrocardiogram in acute coronary syndromes. JAMA. 1999;281:707-713. Copyright © 1999, American Medical Association. All rights reserved. Slide reproduced with permission from Cannon CP. Atherothrombosis slide compendium. Available at: www.theheart.org. Cumulative Mortality (%) 0 2 4 6 8 10 0 30 60 90 120 150 180 Days From Randomization T-wave inversion ST  ACS STEMI with fibrinolytics
  19. 19. Braunwald Classification of Risk for Patients with Unstable Angina Available at: www.acc.org/clinical/guidelines/unstable/unstable.pdf. Normal Slightly elevated (TnT >0.01 but <0.1 ng/mL) Elevated (TnT or TnI >0.1 mg/mL) Cardiac Markers Normal or unchanged ECG during an episode of chest discomfort <ul><li>T-wave inversions >0.2 mV </li></ul><ul><li>Pathological Q waves </li></ul><ul><li>Angina at rest with transient ST-segment changes >0.05 mV </li></ul><ul><li>New or presumed new BBB </li></ul><ul><li>Sustained ventricular tachycardia </li></ul>ECG Age > 70 years <ul><li>Pulmonary edema </li></ul><ul><li>New or worsening MR murmur </li></ul><ul><li>S 3 or new/worsening rale </li></ul><ul><li>Hypotension, bradycardia, tachycardia </li></ul><ul><li>Age >75 years </li></ul>Clinical Findings New-onset or progressive CCS Class III or IV angina the past 2 weeks Prolonged (>20 min) rest angina, now resolved, with moderate or high likelihood of CAD Prolonged ongoing (>20 min) rest pain Character of Pain Prior MI, peripheral or cerebrovascular disease, CABG, or prior aspirin use Accelerating tempo of ischemic symptoms in preceding 48 hrs History Low Risk No high- or intermediate-risk feature but may have any of the following features: Intermediate Risk No high-risk feature but must have 1 of the following: High Risk At least 1 of the following features must be present: Feature
  20. 20. TIMI Risk Score <ul><li>Age > 65 years </li></ul><ul><li>> 3 CAD Risk Factors </li></ul><ul><li>Prior Coronary Stenosis >50 % </li></ul><ul><li>ST deviation </li></ul><ul><li>> 2 Anginal events < 24 hours </li></ul><ul><li>ASA in last 7 days </li></ul><ul><li>Elevated Cardiac Markers (CK-MB or troponin) </li></ul>Reproduced with permission from Antman EM, Cohen M, Bernink PJ, et al. The TIMI risk score for unstable angina/non-ST elevation MI: a method for prognostication and therapeutic decision making. JAMA. 2000;284:835-842. Copyright © 2000, American Medical Association. All rights reserved.
  21. 21. The TIMI Risk Score and Incidence of Adverse Ischemic Events in Patients with NSTE-ACS Reproduced with permission from Antman EM, Cohen M, Bernink PJ, et al. The TIMI risk score for unstable angina/non-ST elevation MI: a method for prognostication and therapeutic decision making. JAMA.. 2000;284:835-842. Copyright © 2000, American Medical Association. All rights reserved. 4.7 8.3 13.2 19.9 26.2 40.9 0 10 20 30 40 50 0/1 2 3 4 5 6/7 Number of Risk Factors Death, MI, or Urgent Revascularization (%)
  22. 22. Troponin I Levels and Mortality in Patients with NSTE-ACS 0 2 4 6 8 0- <0.4 0.4- <1.0 1.0- <2.0 2.0- <5.0 5.0- <9.0 >9.0 % Mortality at 42 Days Adapted with permission from Antman EA, Tanasijevic MJ, Thompson B, et al. Cardiac-specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes. N Engl J Med. 1996;335:1342-1349. Copyright © 1996, Massachusetts Medical Society. All rights reserved. Troponin I Level
  23. 23. Prognostic Value of Troponin T or I in ACS: A Meta-Analysis 1.9 6.7 6.4 20.8 0 5 10 15 20 25 Death Death/MI % RR 3.9 (2.9-5.3) RR 3.8 (2.6-5.5 ) Figure reproduced with permission from Heidenreich PA, Alloggiamento T, Melsop K, et al. The prognostic value of troponin in patients with non-ST elevation acute coronary syndrome: a meta-analysis. J Am Coll Cardiol. 2001;38:478-485. Slide modified with permission from Cannon CP. Atherothrombosis slide compendium. Available at: www.theheart.org. Neg Pos (Trop I + T)
  24. 24. B-type Natriuretic Peptide (BNP) and Mortality in ACS Patients Figure reproduced with permission from de Lemos JA, Morrow DA, Bentley JH, et al. The prognostic value of B-type natriuretic peptide in patients with acute coronary syndrome. N Engl J Med. 2001;345:1014-1021.Copyright © 2001, Massachusetts Medical Society. All rights reserved. Slide modified with permission from Cannon CP. Atherothrombosis slide compendium. Available at: www.theheart.org. 0 2 4 6 8 10 Mortality (%) 0 50 100 150 200 250 300 Days After Randomization P <.001 Quartile 4 (n=630) Quartile 3 (n=632) Quartile 2 (n=632) Quartile 1 (n=631)
  25. 25. Predictive Value of hs-CRP for Mortality from ACS in FRISC Substudy Figure reproduced with permission from Lindahl B, Toss H, Siegbahn A, et al. Markers of myocardial damage and inflammation in relation to long-term mortality in unstable coronary artery disease. FRISC Study Group. Fragmin during Instability in Coronary Artery Disease. N Engl J Med. 2000;343:1139-1147. Copyright © 2000, Massachusetts Medical Society. All rights reserved. Slide modified with permission from Cannon CP. Atherothrombosis slide compendium. Available at: www.theheart.org. Cumulative Probability of Death (%) Months CRP 2-10mg/l (n=294) 20 10 0 0 6 12 18 24 30 36 42 48 CRP >10mg/l (n=309) CRP <2mg/l (n=314)
  26. 26. Initial Therapies and Management
  27. 27. ACC/AHA Class I Recommendations for Initial Management and Anti-Ischemic Therapy <ul><li>Bed rest </li></ul><ul><li>Continuous ECG Monitoring </li></ul><ul><li>Supplemental O 2 to maintain SaO 2 >90% </li></ul><ul><li>NTG (IV or PO as dictated clinically) </li></ul><ul><li>Beta-blockers (PO and/or IV) </li></ul><ul><li>IV Morphine prn pain, anxiety, and/or CHF </li></ul><ul><li>IABP for hemodynamic instability </li></ul><ul><li>ACEI for persistent hypertension in patients with LV systolic dysfunction or CHF </li></ul>Available at: www.acc.org/clinical/guidelines/unstable/unstable.pdf.
  28. 28. Platelets and Anti-Platelet Therapies
  29. 29. Pathogenesis of Acute Coronary Syndromes: The integral role of platelets Plaque Fissure or Rupture Platelet Aggregation Platelet Activation Platelet Adhesion Thrombotic Occlusion
  30. 30. The Role of Platelets in Atherothrombosis Adhesion Aggregation 3 Reproduced with permission from Cannon CP. Atherothrombosis slide compendium. Available at: www.theheart.org. 1 Activation 2
  31. 31. <ul><li>Ticlopidine </li></ul><ul><li>Clopidogrel </li></ul><ul><li>Heparin </li></ul><ul><li>LMW Heparin </li></ul><ul><li>Direct Thrombin Inhibitors </li></ul><ul><li>Aspirin </li></ul>IIb/IIIa receptors fibrin The Platelet <ul><li>GP IIb/IIIa inhibitors </li></ul>ADP Epinephrine Collagen Arachidonic Acid Thrombin
  32. 32. Platelet Inhibition With GP IIb/IIIa Inhibitors Reproduced with permission from Yeghiazarians Y, Braunstein JB, Askari A, et al. Unstable angina pectoris. N Engl J Med. 2000;342:101-114. Copyright © 2000, Massachusetts Medical Society. All rights reserved.
  33. 33. placebo aspirin heparin ASA+hep 0 2 4 6 8 10 12 % Developing MI Treatment Treatment of Unstable Angina Results of a study from the Montreal Heart Institute Data from Theroux P, Quimet H, McCans J, et al. Aspirin, heparin, or both to treat acute unstable angina. N Engl J Med. 1988;319:1105-1111.
  34. 34. The Primary Composite End Point in the CURE Trial Reproduced with permission from Yusuf S, Zhao F, Mehta SR, et al . Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001;345:494-502. Copyright © 2001, Massachusetts Medical Society. All rights reserved. 2 4 6 8 10 12 14 % With Event Clopidogrel + Aspirin 3 6 9 Placebo + Aspirin Follow-up (months) P =.00009 0 12 20% RRR
  35. 35. CURE Bleeding Complications Data from Yusuf S, Zhao F, Mehta SR, et al . Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001;345:494-502.
  36. 36. CURE: Primary End Point in Subgroups Data from Yusuf S, Zhao F, Mehta SR, et al . Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001;345:494-502. 0.79 11.5% 14.3% ST Changes 0.81 10.7% 13.1% Enzyme Elevation 0.79 8.1% 10.1% No Post-Random Revascularization 0.81 11.4% 13.9% Post-Randomization Revascularization 0.79 8.8% 10.9% No Enzyme Elevation 0.80 7.0% 8.7% No ST Changes RR Plavix Placebo Subgroup
  37. 37. CURE Secondary End Points Data from Yusuf S, Zhao F, Mehta SR, et al . Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001;345:494-502. NA 0.93 8.8% 9.4% Refract Ischemia 0.0004 0.88 16.68% 19.02% CV Death/MI CVA/Ref Ischemia 0.03 1.34 3.6% 2.7% Major Bleeding NA 0.85 1.2% 1.4% Stroke <0.01 0.77 5.19% 6.68% MI NA 0.92 5.06% 5.4% CV Death 0.00005 0.80 9.28% 11.7% CV Death/ MI/CVA P Value RR Plavix Placebo Endpoint
  38. 38. PRISM-PLUS: MI/Death Event Rates 2 Days 7 Days 30 Days RR=43% P =0.006 8.3 4.9 RR=30% P =0.03 11.9 8.7 % Patients RR=66% P =0.01 2.6 0.9 Data from PRISM-PLUS Study Investigators. N Engl J Med. 1998;338:1488-1497. Placebo + heparin Aggrastat + heparin
  39. 39. PURSUIT Primary End Point Reproduced with permission from the PURSUIT Trial Investigators. Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes. Platelet glycoprotein IIb/IIIa in unstable angina: Receptor Suppression Using Integrilin Therapy. N Engl J Med. 1998;339:436-443. Copyright © 1998, Massachusetts Medical Society. All rights reserved.
  40. 40. PURSUIT Primary Composite End Point % With Death or MI 0 2 4 6 8 10 12 14 16 Integrilin 9.1% 7.6% 11.6% 10.1% 15.7% 14.2% (n=79) (n=66) (n=118) (n=103) Not powered for statistical analysis 96 Hrs 7 Days 30 Days Placebo Reproduced with permission from the PURSUIT Trial Investigators. Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes. Platelet glycoprotein IIb/IIIa in unstable angina: Receptor Suppression Using Integrilin Therapy. N Engl J Med. 1998;339:436-443. Copyright © 1998, Massachusetts Medical Society. All rights reserved. P=0.01 P=0.02 P=0.04
  41. 41. Subgroup Analyses from the PURSUIT Study Reproduced with permission from the PURSUIT Trial Investigators. Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes. Platelet glycoprotein IIb/IIIa in unstable angina: Receptor Suppression Using Integrilin Therapy. N Engl J Med. 1998;339:436-443. Copyright © 1998, Massachusetts Medical Society. All rights reserved.
  42. 42. Meta-Analysis of IV GP IIb/IIIa Inhibitors in NSTE-ACS: Death or MI at 30 Days PRISM 7.1% 5.8%* 0.80 0.60-1.06 PRISM-PLUS 12.0% 8.7% 0.70 0.50-0.98 13.6%* 1.17 0.80-1.70 PARAGON-A 11.7% 10.3% 0.87 0.58-1.29 12.3% 1.06 0.72-1.55 PURSUIT 15.7% 13.4% 0.83 0.70-0.99 14.2% 0.89 0.79-1.00 PARAGON-B 11.4% 10.6% 0.92 0.77-1.09 GUSTO-IV 8.0% (24h) 8.2% 1.02 0.83-1.24 (48h) 9.1% 1.15 0.94-1.39 Overall 11.8% 10.8% t 0.91 0.85-0.98 Odds Ratio Placebo IV Gp IIb/IIIa 95% CI Placebo Better Gp IIb/IIIa Better 0 1.0 2.0 Study P =.015 * Without heparin. † With/without heparin. (l), Low dose; (h), High-dose. Adapted with permission from Boersma E, Harrington RA, Moliterno DJ, et al. Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndrome: a meta-analysis of all major randomised clinical trials. Lancet. 2002;359:189-198. Slide reproduced with permission from Cannon CP. Atherothrombosis slide compendium. Available at: www.theheart.org.
  43. 43. GP IIb/IIIa Inhibitor NSTE-ACS Studies Analysis Risk-Adjusted Mortality at 30 Days Data from (1) Peterson ED, Pollack CV Jr, Roe MT, et al. Early use of glycoprotein IIb/IIIa inhibitors in non-ST-elevation acute myocardial infarction: observations from the National Registry of Myocardial Infarction 4. J Am Coll Cardiol. 2003;42:45-53 and (2) Boersma E, Harrington RA, Moliterno DJ, et al. Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndrome: a meta-analysis of all major randomised clinical trials. Lancet. 2002;359:189-198. Slide r eproduced with permission from Cannon CP. Atherothrombosis slide compendium. Available at: www.theheart.org. 0.5 2.0 1.0 NRMI 1 Boersma 2 0.83-1.01 0.91 0.79-0.97 0.88 95% CI Odds Ratio Odds Ratio for Mortality at 30 Days GP IIb/IIIa Inhibitor Favored (aspirin + heparin) Control Arm Favored (aspirin + heparin)
  44. 44. GP IIb/IIIa Therapy and Mortality (30 day) in Diabetics with NSTE-ACS 0.5 1.0 1.5 2.0 0 PARAGON A PARAGON B Pooled Relative Risk of Death (versus placebo Rx) GUSTO IV PRISM-PLUS PRISM PURSUIT Mortality: 6.2% vs. 4.6% OR=0.74 CI=0.59-0.92 P=0.007 Adapted with permission from Roffi M, et al. Circulation. 2001;104:2767-2771.
  45. 45. GP IIb/IIIa Dosing and Administration for Up-Front Therapy in Patients with NSTE-ACS <ul><li>Dosing: </li></ul><ul><ul><li>Integrilin: 180 mcg/kg bolus (over 1-2 min), then 2 mcg/kg/min continuous infusion </li></ul></ul><ul><ul><li>Aggrastat: Initial 0.4 mcg/kg/min for 30 min, then continuous infusion at 0.1 mcg/kg/min </li></ul></ul><ul><li>Always also treat with ASA and some form of heparin (UFH or LMWH) </li></ul><ul><li>Patients most commonly treated 2-4 days </li></ul><ul><li>Follow platelet count qD and D/C for significant fall </li></ul><ul><li>Adjust doses for renal insufficiency : </li></ul><ul><ul><li>Integrilin: For creatinine 2-4 mg/dL, decrease infusion to 1 mcg/kg/min; avoid if creatinine >4 mg/dL </li></ul></ul><ul><ul><li>Aggrastat: For CrCl < 30 mL/min, cut all doses in 1/2 </li></ul></ul>
  46. 46. ACC/AHA Recommendations for Antiplatelet Therapy in Patients with NSTE-ACS <ul><li>Class I </li></ul><ul><ul><li>ASA </li></ul></ul><ul><ul><li>Clopidogrel if ASA-allergic or intolerant </li></ul></ul><ul><ul><li>Clopidogrel in addition to ASA if early invasive approach not planned </li></ul></ul><ul><ul><li>Clopidogrel should be withheld for 5-7 days if CABG planned </li></ul></ul><ul><ul><li>GP IIb/IIIa inhibitor if cardiac cath and PCI planned </li></ul></ul><ul><li>Class IIa </li></ul><ul><ul><li>GP IIb/IIIa inhibitor in patients with high-risk features if invasive strategy not planned </li></ul></ul><ul><ul><li>GP IIb/IIIa inhibitor in patients receiving clopidogrel if cardiac cath and PCI planned </li></ul></ul><ul><li>Class IIb </li></ul><ul><ul><li>GP IIb/IIIa inhibitor in patients without high-risk features and PCI not planned </li></ul></ul><ul><li>Class III </li></ul><ul><ul><li>Abciximab in patients in whom PCI is not planned </li></ul></ul>Available at: www.acc.org/clinical/guidelines/unstable/unstable.pdf.
  47. 47. Contraindications to GP IIb/IIIa Rx <ul><ul><ul><li>Active or recent bleeding (4-6 weeks) </li></ul></ul></ul><ul><ul><ul><li>Severe hypertension (SBP >180-200 mm Hg; DBP >110 mm Hg) </li></ul></ul></ul><ul><ul><ul><li>Any hemorrhagic CVA (+/- intracranial neoplasm, AVM, or aneurysm) </li></ul></ul></ul><ul><ul><ul><li>Any CVA within 30 days – 2 years </li></ul></ul></ul><ul><ul><ul><li>Major surgery or trauma within 4-6 weeks </li></ul></ul></ul><ul><ul><ul><li>Thrombocytopenia ( <100,000/mm 3 ) </li></ul></ul></ul><ul><ul><ul><li>Bleeding diathesis/warfarin with elevated INR </li></ul></ul></ul><ul><ul><ul><li>(Doses must be avoided with renal insufficiency or failure) </li></ul></ul></ul>
  48. 48. Antithrombin Therapy Studies and Recommendations
  49. 49. RR: Death/MI ASA Alone 68/655=10.4% Heparin + ASA 55/698=7.9% 0.1 1 10 Summary Relative Risk 0.67 (0.44-0.1.02) Theroux RISC Cohen 1990 ATACS Holdright Gurfinkel Comparison of Heparin + ASA vs ASA Alone ASA indicates acetylsalicylic acid; RISC, Research on InStability in Coronary artery disease; ATACS, Antithrombotic Therapy in Acute Company Syndromes; RR, relative risk; and MI, myocardial infarction. Data from Oler A, Whooley MA, Oler J, et al. Adding heparin to aspirin reduces the incidence of myocardial infarction and death in patients with unstable angina: a meta-analysis. JAMA. 1996;276:811-815. Slide reproduced with permission from Cannon CP. Atherothrombosis slide compendium. Available at: www.theheart.org.
  50. 50. ESSENCE Results 30% 25% 20% 15% 10% 0 9 13 Days After Randomization 17 21 5 5% 25 29 Unfractionated Heparin Enoxaparin (Lovenox) Death, MI or Recurrent Angina P = 0.02 Risk Reduction 16.2% Adapted with permission from Cohen M, Demers C, Gurfinkel EP, et al. A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study Group. N Engl J Med. 1997;337:447-452. Copyright © 1997, Massachusetts Medical Society. All rights reserved.
  51. 51. Death, MI or Urgent Revascularization Unfractionated Heparin Enoxaparin (Lovenox) Days 20 16 12 8 4 2 4 6 8 10 12 14 0 p = 0.03 Relative Risk Reduction = 15% TIMI 11B: Enoxaparin vs. Heparin in NSTE-ACS Adapted from Antman EM, et al. Circulation. 1999;100:1593-1601. 1 6 . 7 % 1 4 . 2 %
  52. 52. Guidelines for the Use of Enoxaparin in Patients with NSTE-ACS <ul><li>1 mg/kg SQ q12 hours (actual body weight) </li></ul><ul><ul><li>An initial 30 mg IV dose can be considered </li></ul></ul><ul><li>Adjust dosing if CrCl <30 cc/min </li></ul><ul><ul><li>1 mg/kg SQ q24 hours </li></ul></ul><ul><li>Do not follow PTT; do not adjust based on PTT </li></ul><ul><li>Stop if platelets  by 50% or below 100,000/mm 3 </li></ul><ul><li>If patient to undergo PCI: </li></ul><ul><ul><li>0-8 hours since last SQ dose: no additional antithrombin therapy </li></ul></ul><ul><ul><li>8-12 hours since last SQ dose: 0.3 mg/kg IV immediately prior to PCI </li></ul></ul>
  53. 53. ACC/AHA Recommendations for Antithrombin Therapy in Patients with NSTE-ACS <ul><li>Class I </li></ul><ul><ul><li>Anticoagulation with subcutaneous LMWH or intravenous UFH should be added to antiplatelet therapy </li></ul></ul><ul><ul><li>Dose of UFH 60-70 U/kg (max 5000) IV followed by infusion of 12-15 U/kg/hr (initial max 1000 U/hr) titrated to aPTT 1.5-2.5 times control </li></ul></ul><ul><ul><li>Dose of enoxaparin 1 mg/kg subcutaneously q12 hr; the first dose may be preceded by a 30-mg IV bolus </li></ul></ul><ul><li>Class IIa </li></ul><ul><ul><li>Enoxaparin is preferable to UFH as an anticoagulant unless CABG is planned within 24 hours </li></ul></ul>Available at: www.acc.org/clinical/guidelines/unstable/unstable.pdf.
  54. 54. Early Invasive Strategy Studies and Recommendations in Patients with NSTE-ACS
  55. 55. TACTICS Months 4% 20% 16% 12% 8% 1 2 3 4 5 6 15.9% 19.4% Initial Medical Rx Early Cath + PTCA Adapted with permission from Cannon CP, Weintraub WS, Demopoulos LA, et al. Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban. N Engl J Med. 2001;344:1879-1887. Copyright © 2001, Massachusetts Medical Society. All rights reserved.
  56. 56. TACTICS Trial Results Based on Troponin Negative Troponin Positive Troponin 5% 10% 15% 20% 25% P=NS P<0.001 Adapted with permission from Cannon CP, Weintraub WS, Demopoulos LA, et al. Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban. N Engl J Med. 2001;344:1879-1887. Copyright © 2001, Massachusetts Medical Society. All rights reserved. Initial Medical Rx Early Cath + PTCA
  57. 57. TnT indicates troponin T; and ST, ST segment. Data from (1) Morrow DA, et al. JAMA. 2001;286:2405-2412 and (2) Cannon CP, et al. N Engl J Med . 2001;344:1879-1887. Slide reproduced with permission from Cannon CP. Atherothrombosis slide compendium. Available at: www.theheart.org. Benefit of Invasive Strategy by Troponin and ST Changes Death, MI, or Rehospitalization for ACS at 6 Months 12.4 25.0* 16.0 15.3* 0 5 10 15 20 25 30 TnT – TnT + CV Events (%) P =NS 15.1 24.5* 16.6 16.4* 0 5 10 15 20 25 30 No ST change ST change P =NS P <.001 P <.001 Conservative Invasive
  58. 58. The Primary Composite Ischemic End Point in RITA-3 Reproduced with permission from Fox KA, Poole-Wilson PA, Henderson RA, et al. Interventional versus conservative treatment for patients with unstable angina or non-ST-elevation myocardial infarction: the British Heart Foundation RITA 3 randomised trial. Randomised Intervention Trial of Unstable Angina. Lancet. 2002;360:743-751.
  59. 59. Meta-Analysis of Trials of Early Cardiac Cath and Revascularization Versus Initial Medical Therapy Alone in Patients with NSTE-ACS Reproduced with permission from Fox KA, Poole-Wilson PA, Henderson RA, et al. Interventional versus conservative treatment for patients with unstable angina or non-ST-elevation myocardial infarction: the British Heart Foundation RITA 3 randomised trial. Randomised Intervention Trial of unstable Angina. Lancet. 2002;360:743-751.
  60. 60. Invasive vs Conservative Strategy for UA/NSTEMI UA indicates unstable angina, NSTEMI, non–ST-segment myocardial infarction; ISAR, Intracoronary Stenting and Antithrombic Regimen Trial; RITA, Randomized Intervention Treatment of Angina; VANQWISH, Veterans Affairs Non-Q-Wave Infarction Strategies in Hospital study; MATE, Medicine vs Angioplasty for Thrombolytic Exclusions trial; TACTICS-TIMI18, Treat Angina with Aggrastat ® and Determine Cost of Therapy with Invasive or Conservative Strategy; and FRISC, Fragmin during InStability in Coronary artery disease. TIMI IIIB 2003 Conservative Invasive VANQWISH MATE FRISC II TACTICS- TIMI 18 VINO RITA-3 TRUCS ISAR- COOL Slide reproduced with permission from Cannon CP. Atherothrombosis slide compendium. Available at: www.theheart.org.
  61. 61. ACC/AHA Class I Recommendations for Invasive and Medical Strategies in Patients with NSTE-ACS <ul><li>Class I </li></ul><ul><ul><li>An early invasive strategy in patients with any high-risk indicators: </li></ul></ul><ul><ul><ul><li>Recurrent angina/ischemia at rest or with low-level activities </li></ul></ul></ul><ul><ul><ul><li>Elevated troponin </li></ul></ul></ul><ul><ul><ul><li>New or presumed new ST-segment depression </li></ul></ul></ul><ul><ul><ul><li>Recurrent angina/ischemia with CHF Sx and S 3 gallop, pulmonary edema, worsening rales, or new or worsening MR </li></ul></ul></ul><ul><ul><ul><li>High-risk findings on noninvasive stress testing </li></ul></ul></ul><ul><ul><ul><li>Depressed LVEF (<40%) </li></ul></ul></ul><ul><ul><ul><li>Hemodynamic instability </li></ul></ul></ul><ul><ul><ul><li>Sustained ventricular tachycardia </li></ul></ul></ul><ul><ul><ul><li>PCI with 6 months or prior CABG </li></ul></ul></ul><ul><ul><li>In the absence of any of the above high-risk indicators, either an early conservative or an early invasive strategy </li></ul></ul>Available at www.acc.org/clinical/guidelines/unstable/unstable.pdf.
  62. 62. Peri- and Post-Discharge Therapies and Risk Modification
  63. 63. MIRACL: Acute Statin Rx Cumulative Events 5% 10% 15% Time Since Randomization (weeks) 4 8 12 16 RR=0.84 P=0.048 Adapted with permission from Schwartz GG, Olsson AG, Ezekowitz MD, et al. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA. 2001;285:1711-1718. Copyright © 2001, American Medical Association. All rights reserved. 17.4% 14.8% Placebo High-dose statin
  64. 64. PROVE-IT TIMI-22 Trial Primary Results % with Event Months of Follow-up Pravastatin 40mg (26.3%) Atorvastatin 80mg (22.4%) 16% RR (P = 0.005) 30 25 20 15 10 5 0 Courtesy of and reproduced with permission from C.P. Cannon. 0 3 18 21 24 27 30 6 9 12 15
  65. 65. ACC/AHA Class I Recommendations for Long-Term Medical Therapy in Patients with NSTE-ACS <ul><li>Class I </li></ul><ul><ul><li>Aspirin 75-325 mg qD </li></ul></ul><ul><ul><li>Clopidogrel 75 mg qD when ASA is not tolerated because of hypersensitivity or GI intolerance </li></ul></ul><ul><ul><li>Combined ASA + clopidogrel for 9 months after NSTE-ACS </li></ul></ul><ul><ul><li>Beta blockers unless contraindicated </li></ul></ul><ul><ul><li>Lipid-lower agents and diet if LDL > 100-130 mg/dL </li></ul></ul><ul><ul><li>ACEI for patients with CHF, LV dysfunction (EF <40%), hypertension, or diabetes </li></ul></ul>Available at: www.acc.org/clinical/guidelines/unstable/unstable.pdf.
  66. 66. ACC/AHA Class I Recommendations for Long-Term Risk Factor Modification in Patients with NSTE-ACS <ul><li>Class I </li></ul><ul><ul><li>Specific instruction on smoking cessation </li></ul></ul><ul><ul><li>Specific instruction on optimal weight, diet, and daily exercise </li></ul></ul><ul><ul><li>Lipid-lowering therapy (statin) for LDL >100-130 mg/dL </li></ul></ul><ul><ul><li>A fibrate or niacin if HDL <40 mg/dL occurring as an isolated finding or in combination with other lipid abnormalities </li></ul></ul><ul><ul><li>Hypertension control to a BP of <130/85 mm Hg </li></ul></ul><ul><ul><li>Tight control of hyperglycemia in diabetics </li></ul></ul>Available at: www.acc.org/clinical/guidelines/unstable/unstable.pdf.

×