Acute Coronary Syndrome. ACC/AHA 2002 Guidelines

Transcription

1 Acute Coronary Syndrome ACC/AHA 2002 Guidelines

2 ACS Unstable Angina Non ST elevation MI ST elevation MI

3 ACS UA and Non STEMI described in these guidelines Management of STEMI described in separate guidelines

4 ACS UA and Non-STEMI share pathophysiology and clinical presentations Differ in presence or absence of biomarker evidence for myonecrosis UA patients without biomarker or EKG abnormalities will have a higher probability of non-cardiac pain

5 Scope of Problem 5.3 million ER visits/year with chest pain 1.5 million hospitalizations/year 60% patients are over 65 years 46% female

6 Mortality of Patients With ACS: GRACE Registry % Mortality UA NSTEMI STEMI n=24,055 n=16, In Hospital Hospital 6 Months Goldberg. Am J Cardiol ;93:288.

7 Pathophysiology of ACS Progressive mechanical obstruction Non-occlusive thrombus on pre-existing plaque Inflammation Dynamic obstruction (vasospasm) Secondary to extrinsic precipitating condition

8 Pathophysiology of ACS

9 Pathophysiology of ACS

10 Pathophysiology of ACS

11 Pathophysiology of ACS Buffon, A, et al. NEJM, July 4, 2002, 347:5-12

12 Presentations of ACS Rest angina New-onset angina Increasing angina

13 ACS Many patients initially diagnosed with possible ACS will ultimately be found to be free of ischemic disease Important in deciding how aggressive to be at outset

14 Risk Stratification High likelihood of ischemia History: symptoms similar to prior episode, previously diagnosed CAD Exam: transient MR, low BP, rales, diaphoresis EKG: new ST deviations or T-wave inversions Markers: troponin, ck-mb s

15 Risk Stratification Intermediate likelihood of ischemia History:Chest or left arm discomfort, age >70, diabetes Exam: extracardiac vascular disease EKG: Q-waves, ST or T wave abnormalities not demonstrated to be new Markers: normal

16 Risk Stratification Low likelihood of ischemia History: pleuritic, sharp, focal, brief, or prolonged pain; radiation to legs Exam: chest wall tenderness EKG: normal or non-specific Markers: normal

17 7 point score TIMI Risk Score Age>65 3 or more CAD risk factors Prior CAD by cath ST segment deviation 3 episode angina in 24 hours ASA use within 7 days Positive markers

18 TIMI Risk Score Validated to correlate with risk of death, reinfarction, recurrent ischemia in 3 trials Increasing benefit of newer strategies and invasive strategies with increasing score Tempo of angina and prior MI most potent predictors of death

19 Cardiac Biomarkers Creatine Kinase CK-MB CK-MB index Troponin TnI and TnT Prognostic importance Myoglobin

20 Cardiac Biomarkers

21 Cardiac Biomarkers Troponin Prognostic Ability CAPTURE trial of abciximab Tn positive: 23.9% placebo vs.9.5% treated Tn negative: 7.5% placebo vs. 9.4% treated trop + trop - placebo abcix

22 ACS Hospital Management

23 Anti-ischemic Therapy Class I Bedrest, EKG monitoring Nitrates Pulse oximetry and oxygen prn Morphine for pain, congestion, agitation Beta blockers CCB if Beta blockers contraindicated ACE-I for HTN with LV dysfunction, CHF or diabetes

24 Anti-ischemic Therapy Class II a CCB if chest pain persists ACE-I for all ACS patients IABP for patients with persistent severe ischemia Class II b CCB instead of Beta blocker Immediate release CCB with Beta blocker Class III Nitrate within 24 hours of ED drug Immediate release CCB without Beta blocker

25 Antiplatelet and Anticoagulation Therapy

26 ASA in UA/NSTEMI Death or MI % of Patients Plac. ASA 0 Plac. ASA 0 Plac. ASA 0 Plac. ASA Lewis et al. NEJM 1983;309: Cairns, etal. NEJM 1985;313: Theroux, etal. NEJM 1988;319: RISC Group.Lancet 1990;336:

27 ATC 2002: Indirect Comparisons ASA Doses on Vascular Events in High Risk Patients ASA Dose # Trials OR mg 34 19% mg 19 26% mg 12 32% <75 mg 3 13% Overall 65 23% Antiplatelet Better Antithrombotic Trialists Collaboration BMJ 2002; 324:71-86 Antiplatelet Worse

28 Randomized Trials of Aspirin in UA/NSTEMI Trial ASA Treatment Length of Follow-up RRR P Value Veterans Affairs Study (1983) 325 mg/d * 3 mo 41%.004 Canadian Study (1985) 325 mg 4x daily 18 mo 30%.072 Montreal Heart Study (1988) 650 mg first dose, 325 mg/d 6 d 63%.04 RISC (1990) 75 mg for 3 months* 13 mo 64%.0001 ATC meta-analysis (2002) Various regimens* Various 46%.0001

29 CURE Study Primary End Point MI/Stroke/CV Death Cumulative Hazard Rate Placebo + ASA* Clopidogrel + ASA* 20% Relative Risk Reduction P = N = 12, Months of Follow-Up The CURE Trial Investigators. N Engl J Med. 2001;345:

30 PCI CURE: Benefit of Pre-treatment with Clopidogrel at 30 Days Cumulative Hazard Rate * In combination with standard therapy Cardiovascular death, MI, or urgent revascularization Placebo + ASA* Days of follow-up Mehta, SR. et al for the CURE Trial Investigators. Lancet. August 2001;21: % 4.5 % Clopidogrel + ASA* 30% RRR P = 0.03 N = 2658

31 PCI-CURE Overall Long-term Results CV Death or MI from randomization to end of follow-up 0.15 Placebo + ASA* Cumulative Hazard Rate * In addition to other standard therapies. Clopidogrel + ASA* 12.6% 8.8% P = N = Days of follow-up Mehta et al for the CURE Investigators. Lancet. 2001;358: % Relative Risk Reduction

32 Cure Study: Bleeding Results to 1 Year Event Clopidogrel + ASA* n = 6,259 Placebo + ASA* n = 6,303 P value Major bleeding 3.7% 2.7% Life-threatening bleeding 2.2% 1.8% 0.13 Other major bleeding 1.6% 1.0% Minor bleeding 5.1% 2.4% <0.001 *Other standard therapies were used as appropriate. Life-threatening and other major bleeding. The CURE Trial Investigators. N Engl J Med. 2001;345: PLAVIX Prescribing Information

33 IIb/IIIa Inhibitors in ACS

34 IIb/IIIa Inhibitors in ACS % Death or MI at 30 Days Trial drug placebo IIb/IIIa RR P PRISM + Tiro PRISM Tiro PURSUIT Epti PARAGON Lami GUSTO IV Abcix All ACS <0.001

35 Platelet GP IIb/IIIa Inhibitors in ACS 30-Day Mortality: Benefit in Diabetics Trial PURSUIT PRISM N Diabetics N Nondiabetics PRISM-PLUS PLUS GUSTO IV PARAGON A PARAGON B Pooled P= ,072 P=.99 Roffi. Circulation ;104: GP IIb/IIIa Better Placebo Better GP IIb/IIIa Better Placebo Better

36 Summary of Efficacy and Safety of Antiplatelet Therapy in UA/NSTEMI Death or MI (%) Major Bleeding (%) Therapy N Drug Control RR Drug Control RR ASA % % Clopidogrel 12, % % GP IIb/IIIa 31, % % Mehta. J Am Coll Cardiol ;41:79S.

37 Antiplatelet and Anticoagulation Class I: Antiplatelet Therapy ASA on presentation and indefinitely Clopidogrel for patients intolerant of ASA For non-pci patients, clopidogrel on presentation and then 1-9 months For PCI patients, clopidogrel for 1-9 months Hold clopidogrel 5-7 days before CABG

38 Antiplatelet and Anticoagulation Class I: Anticoagulation Subcutaneous LMWH or IV UFH should be added to antiplatelet therapy with ASA and/or clopidogrel A platelet GP IIb/IIIa antagonist should be added to patients for whom PCI is anticipated

39 Antiplatelet and Anticoagulation Class IIa Eptifibatide or tirofiban should be administered, in addition to ASA and LMWH or UFH, to patients with continuing ischemia, an elevated troponin or with other high-risk features in whom an invasive management strategy is not planned

40 Antiplatelet and Anticoagulation Class IIa Enoxaparin is preferable to UFH unless CABG is planned within 24 h A platelet GP IIb/IIIa antagonist should be administered to patients already receiving heparin, ASA, and clopidogrel in whom catheterization and PCI are planned. The GP IIb/IIIa antagonist may also be administered just prior to PCI

41 Antiplatelet and Anticoagulation Class IIb Eptifibatide or tirofiban, in addition to ASA and LMWH or UFH, to patients without continuing ischemia who have no other high-risk features and in whom PCI is not planned

42 Antiplatelet and Anticoagulation Class III 1. Intravenous fibrinolytic therapy in patients without acute ST-segment elevation, a true posterior MI, or a presumed new left bundle-branch block 2. Abciximab administration in patients in whom PCI is not planned

43 % Pts TIMI 11B: Early Phase Death/MI/Urgent Revasc UFH (n=1957) ENOX (n=1953) 7.3 % 5.5 % RRR 24% P= Hours from Randomization Antman, Circulation 1999;100:

44 SYNERGY Trial Subcutaneous enoxaparin (n = 4993) or intravenous unfractionated heparin (n = 4985) in patients with ACS anticipating invasive evaluation The primary end point occurred in 14.0% (696/4993) of patients assigned to enoxaparin and 14.5% (722/4985) of patients assigned to unfractionated heparin (p = N.S.) JAMA ; 292: 45-54, July 7, 2004

45 SYNERGY Trial

46 SYNERGY Trial More bleeding was observed with enoxaparin, with a statistically significant increase in TIMI major bleeding (9.1% vs. 7.6%, P =.008) Enoxaparin may be appropriate in patients anticipating conservative therapy and UFH appropriate in patients anticipating invasive therapy

47 Risk Stratification

48 Risk Stratification Antman,EM, et al. NEJM, 1996; 335:1342-9

49 Antiplatelet and Anticoagulation

50 Conservative Vs. Invasive Strategies Conservative Strategy: Coronary angiography reserved only for patients with recurrent ischemia or strongly positive stress test Invasive Strategy: Patients routinely recommended for coronary angiography and revascularization

51 Conservative Vs. Invasive Strategies

52 Conservative Vs. Invasive Strategies Routine vs. Selective Invasive Strategies in Patients with Acute Coronary Syndromes: A Collaborative Meta Analysis of Randomized Trials total of 7 trials (N = 9212 patients) Overall, death or MI was reduced from 14.4% in the selective group to 12.2% in the invasive group significant reduction in MI alone of 9.4% vs. 7.3% JAMA. 2005;293:

53 Invasive vs. Conservative Strategy for UA/NSTEMI 2003 ISAR-COOL RITA-3 VANQWISH MATE TIMI IIIB VINO TRUCS TACTICS- TIMI 18 FRISC II Conservative Invasive # Pts:

54 Conservative Vs. Invasive Strategies Class I: Invasive strategy for the following Recurrent ischemia at rest/minimal activity Elevated Troponin ST depression CHF Ejection Fraction less than 40% Hemodynamic instability Sustained ventricular tachycardia PCI within 6 months Prior CABG

55 Conservative Vs. Invasive Strategies Class I In the absence of these findings, either an early conservative or an early invasive strategy in hospitalized patients without contraindications for revascularization. (Level of Evidence: B)

56 Conservative Vs. Invasive Strategies Class II a Early invasive strategy in patients with repeated presentations for ACS despite therapy and without evidence for ongoing ischemia or high risk. (Level of Evidence: C)

57 Conservative Vs. Invasive Strategies Class III Coronary angiography in patients with extensive comorbidities (e.g., liver or pulmonary failure, cancer), in whom the risks of revascularization are not likely to outweigh the benefits. Coronary angiography in patients with acute chest pain and a low likelihood of ACS. Coronary angiography in patients who will not consent to revascularization regardless of the findings.

58 Conservative Vs. Invasive Strategies de Winter et al. NEJM Sep 15, 2005

59 Conservative Vs. Invasive Strategies Incidence of the Failure of Medical Therapy According to the Number of Risk Factors Present on Admission Yeghiazarians, Y. et al. N Engl J Med 2000;342:

60 Post-Hospital Care Goals of continued medical therapy Prognostic benefits: ASA, Beta blockers, lipid agents, ACE-I s for low EF Control of ischemia: nitrates, Beta blockers, calcium channel blockers Treatment of risk factors: HTN, smoking, lipids, diabetes

61 Post-Hospital Care Class I Drugs required in the hospital to control ischemia should be continued after hospital discharge in patients who do not undergo coronary revascularization All patients should be given sublingual or spray NTG and instructed in its use. Before discharge, patients should be informed about symptoms of AMI and should be instructed in how to seek help if symptoms occur

62 Class I Post-Hospital Care Aspirin 75 to 325 mg per d in the absence of contraindications Clopidogrel 75 mg daily when ASA is not tolerated because of hypersensitivity or gastrointestinal intolerance. The combination of ASA and clopidogrel for 9 months after UA/NSTEMI Beta-blockers in the absence of contraindications

63 Class I Post-Hospital Care Lipid-lowering agents and diet in post-acs patients with low-density lipoprotein (LDL) cholesterol of greater than 130 mg per dl Lipid-lowering agents if LDL cholesterol level after diet is greater than 100 mg per dl ACEIs for patients with CHF, LV dysfunction (EF less than 0.40), hypertension, or diabetes

64 ACE-I and CAD Risk of MI, Stroke, or CV Death HOPE/HOPE-TOO Study Investigators, Circulation. 2005;112:

65 Post-Hospital Care Intensive Vs. Moderate Lipid Lowering With Statins After ACS Cannon et al. NEJM April 8, 2004

66 Post Hospital Care Role of Inflammation Ridker et al. NEJM Jan 6, 2005

67 Post Hospital Care Other Agents That Target Inflammation Methylprednisolone therapy did not improve the short-term outcome Soluble P-selectin glycoprotein ligand-1 immunoglobulin showed no reduction of infarct size Two different antibodies to leukocyte integrin CD11b/CD showed no reduction of infarct size Pexelizumab, a monoclonal antibody against C5, also failed in 2 trials

68 Post Hospital Care Future of Lipid Lowering Effect of Recombinant ApoA-I Milano on Coronary Atherosclerosis in Patients with Acute Coronary Syndrome ApoA-I Milano is a variant of apolipoprotein A-I identified in individuals in rural Italy who exhibit very low levels of HDL A recombinant ApoA-I Milano/phospholipid complex (ETC-216) produced significant regression of coronary atherosclerosis as measured by IVUS Nissen, SE, et al. JAMA. 2003;290:

69 Performance Matters! Relationship Between Process and Outcome 7 6 % In-Hospital Mortality <65% 65%-75% 75%-80% >80% Hospital Composite Adherence Quartiles