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NSTEMI Acute Coronary Syndromes Patrick Hildbrand.

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Presentation on theme: "NSTEMI Acute Coronary Syndromes Patrick Hildbrand."— Presentation transcript:

1 NSTEMI Acute Coronary Syndromes Patrick Hildbrand

2

3 Trends and Prognosis in NSTEMI Furman MI, JACC 2001, 37: Hospital 1 year

4 Hospital Outcome by Final Diagnosis

5

6 Trends and Prognosis Diagnosis and Risk assessment Initial Management Treatment < Long-Term Management Summary of Treatment Approaches NSTEMI Acute Coronary Syndromes

7 Diagnosis

8 Chest Pain

9 ECG Kaul P, JACC 2001, 38:64-71

10 Biochemistry

11 Risk Stratification

12 Summary Diagnosis and Risk assessment Diagnosis and short-term risk stratification should be based on a combination of Clinical history Symptoms ECG and (10 minutes, 6h, 24h and before hospital discharge) Biomarkers (admission and after 6-12 h) Risk score results Echocardiography is recommended to rule out differential diagnosis Patient without recurrence of pain, normal ECG findings and negative troponins tests > non invasive stress testing

13 Trends and Prognosis Diagnosis and Risk assessment Initial Management Treatment < Long-Term Management Summary of Treatment Approaches NSTEMI Acute Coronary Syndromes

14 Therapeutic Options Anti-ischemic agents Anti-coagulants UFH or LMWH Factor-Xa inhibitors (Fondaparinux) Direct Thrombin inhibitors (Bivalirudin) Anti-platelet agents ASA Clopidrogel GP IIb/IIIa Inhibitors Revascularization NSTEMI

15 Anti-Ischemic Agents Aim: Decrease myocardial oxygen consumption and/or induce vasodilatation Betablockers are recommended in absence of contraindications (hypertension and tachycardia; cave inferior MI, acute LV dysfunction) (IB) Nitrates are effective in symptom relief in the acute management of angina episodes (IC) (Cave: Phospodiesterase-5-inhibitors, RV MI) Calcium channel blockers provide symptom relief in patients already receiving betablockers and nitrates; patient with contraindication to betablockers; vasospastic angina (Ic) Nifedipine or other dihydropyridine should not be used (IIIC) unless combined with betalockers (IIa-B)

16 Anti-ischemic agents Anti-coagulants UFH or LMWH Factor-Xa inhibitors (Fondaparinux) Direct Thrombin inhibitors (Bivalirudin) Anti-platelet agents ASA Clopidrogel GP IIb/IIIa Inhibitors Revascularization NSTEMI

17 UFH LMWH UFH 33% RR

18 Enoxaparin (©Clexane) vs UFH NON REVASC. GP IIb/IIIa Inhibitors GP IIb/IIIa Inhibitors

19 Enoxaparin was non-inferior to UFH in Reducing death or MI in the Synergy Trial Synergy 14% versus 14.5% p=n.s.

20 Factor-Xa inhibitors (Fondaparinux, © Arixtra) Oasis 5 Trial Death, MI or refractory ischemia through day 9

21 Oasisi 5: Major bleeding through d9

22 Relation between bleeding and mortality in OASIS 5 Bleeding carries a high risk of death Prevention of bleeding is as important as prevention of ischemic events and results in a significant rate reduction of death > Risk stratification of bleeding should be part of the decision making process

23 Direct thrombin inhibitors (Bivalirudin, ©Angiox) UFH/LMWH

24 Acuity Trial Primary Endpoint Measures Net clinical outcome Cave: hematoma > 5cm never used in any other definition

25 Summary Anti-coagulants Anticoagulation is recommended for all Patient in addition to anti- platelet therapy Anticoagulation should be selected to the risk of both ischemic and bleeding events Choice of the anticoagulants (UFH, LMWH, fondaparinux and bivalirudin should depend on the strategy. Urgent invasiv UFH (I-C), Enoxaparin (IIa- B) or bivalirudin (I-B) Non-urgent situation Fondaparinux efficacy/safety profile (I-A) Enoxaparin only if bleeding risk is low (IIa-B) >> not LMWH (other then Enoxaparin) / UFH

26 Anti-ischemic agents Anti-coagulants UFH or LMWH Factor-Xa inhibitors (Fondaparinux) Direct Thrombin inhibitors (Bivalirudin) Anti-platelet agents ASA Clopidrogel GP IIb/IIIa Inhibitors Revascularization NSTEMI

27 Anti-platelet agents

28 ASA GI intolerance 5-40%, bleeding >0.9% in CAPRIE

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

30 PCI-CURE Study: CV Death or MI Cumulative Hazard Rate Clopidogrel + Aspirin* (n=1313) 31% Relative Risk Reduction Placebo + Aspirin* (n=1345) Median time to PCI Days of Follow-Up 12.6% 8.8% P=0.002 *In combination with standard therapy. Mehta SR, et al. Lancet. 2001;358:

31 GP IIb/IIIa Inhibitors Tirofiban Eptifibatide Abciximab Lamifibane

32 Acuity timing

33 Summary GP IIb/IIIa Inhibitors Intermediate to high risk (DM, ST segment depression and Troponin pos.) patients, either eptifibatide or tirofibane for initial early treatment is recommended in addition to oral antiplatelet agents (IIa-A) Patient not pre-treated with GP IIb/IIIa inhibitors and proceeding to PCI; abciximab is recommended (IA) GpIIb/IIIa inhibitors must be combined with anticoagulation I-A Bivaluridin may be used as an alternative to GPIIb/IIIa inhibitors plus UFH/LMWH (IIa-B) GPIIb/IIIa inhibitors only for invasive strategy

34 Coronary revascularization Revascularization for NSTEMI is performed to relieve angina relieve ongoing myocardial ischemia prevent progression to MI or death 30-38% single vessel 44-59% mutlivessel disease (TIMI-3B, FRISC-2)

35 Anti-ischemic agents Anti-coagulants UFH or LMWH Factor-Xa inhibitors (Fondaparinux) Direct Thrombin inhibitors (Bivalirudin) Anti-platelet agents ASA Clopidrogel GP IIb/IIIa Inhibitors Revascularization NSTEMI

36 Coronary revascularization

37 Randomized trials comparing early invasive (dark bars) vs. conservative strategy (open bars)

38 Relative Mortality Benefit with the Revascularization vs. Gradient in Rates of Revascularization Between both Randomization Arms

39 Summary Invasive vs. Conservative Strategies New data coming from long-term follow up of RITA-3 and FRISC-2 and Mehta meta-analysis show significant risk reduction for death and „death & MI“ at long-term follow up Early hazard shown in ICTUS Trial Early hazard shown in Mehta meta-analysis ICTUS, Lancet 2007 FRISC 2, Lancet 2000 RITA 3 Lancet 2005 Metha JAMA 2005

40 Summary Treatment Approaches

41 Summary Therapeutic Options Anti-ischemic agents Anti-coagulants UFH or LMWH Factor-Xa inhibitors (Fondaparinux) Direct Thrombin inhibitors (Bivalirudin) Anti-platelet agents ASA Clopidrogel GP IIb/IIIa Inhibitors Revascularization NSTEMI

42 Trends and Prognosis Diagnosis and Risk assessment Initial Management Treatment < Long-Term Management Summary of Treatment Approaches NSTEMI Acute Coronary Syndromes

43 Long-term Post-PCI Management What are our targets ? Prevention of stent thrombosis/restenosis Prevention of plaque rupture

44 ATC 2002: Indirect Comparisons ASA Doses on Vascular Events in High Risk Patients mg34 19% mg19 26% mg12 32% <75 mg 3 13% Overall65 23% Antiplatelet Better Antiplatelet Worse ASA Dose # Trials OR Antithrombotic Trialists’ Collaboration BMJ 2002; 324:71-86

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

46 PCI-CURE Study: CV Death or MI Cumulative Hazard Rate Clopidogrel + Aspirin* (n=1313) 31% Relative Risk Reduction Placebo + Aspirin* (n=1345) Median time to PCI Days of Follow-Up 12.6% 8.8% P=0.002 *In combination with standard therapy. Mehta SR, et al. Lancet. 2001;358:

47 Events Saved vs Life-threatening Bleeding Over Time: Net Clinical Benefit of Clopidogrel Yusuf S et al for the CURE Trial Investigators. Circulation. 2003;107:966

48 ACE-Inhibitors HOPE HOPE: N Engl J Med. 2000;342: P<.001 RRR=22% Follow-Up (days) Patients Reaching Composite End Point [MI, Stroke, CV Death] (%) Ramipril Placebo CV Death, MI, or Cardiac Arrest (%) Placebo annual event rate: 2.4% Perindopril Placebo P=.0003 RRR=20% Years N = 12, EUROPA:. Lancet. 2003;362: PEACE:N Engl J Med. 2004;351: Placebo Trandolapril Incidence of Primary End Point (%) Years After Randomization EUROPA PEACE

49 Leading and Lagging Hospitals Quartiles: Discharge Care # LVEF < 40% * Known hyperlipidemia Peterson et al, ACC 2004

50 Discharge Clopidogrel Use in CRUSADE CRUSADE DATA: Q 4, 2004 – Q 3, 2005 (n=35,897)

51 Proven (  mortality or  death/MI/stroke) Medical Therapies Following (large*) MI Treated with Stent TreatmentRRRAbs benefitCost/mo + Aspirin 1 23%2.4%1.00 Statin 2 (simvastatin)13%1.8% Eplerenone 3 15%2.3% ACE-I* 4 (ramipril)13%1.1%55.99  blockers* 5 (carvedilol)23%3.0% Clopidogrel** 6 27%3.0% Total>70%$ ISIS-2, Lancet HPS, Lancet, Pitt NEJM 2003;348; ACE-I Acute MI Collaborators Overview, Circulation 1998 (ant MI); HOPE. 5. CAPRICORN, Lancet, CREDO, JAMA, 2002 ** death, MI, stroke; all others death costs from january 2007

52 Improving Adherence, Outcome, and Cost by Providing EBM Coverage Post MI: Health Insurance Perspective Choudhry N. Health Affairs 2007;26: After 5 years of medicine coverage with good adherence to prevention - $6,500 saved per patient

53 Disease Modifying Drugs in Atherothrombosis Statins Prevent CV events Prevent progression of CAD Prevents development of DM ACE-Inhibitors/ARB’s Prevent CV events Prevent renal dysfunction in DM Clopidogrel Prevents CV events

54 Long-term Post-PCI Management There are two key targets in the post-PCI management The lesion and the patient ! The use of ASA with clopidogrel should be used in all patients with PCI Long-term use of the combination appears at least to be safe up to about 3 years Important other therapies include statins, ACE/ARB, and beta-blockers There are two key targets in the post-PCI management The lesion and the patient ! The use of ASA with clopidogrel should be used in all patients with PCI Long-term use of the combination appears at least to be safe up to about 3 years Important other therapies include statins, ACE/ARB, and beta-blockers

55 Trends and Prognosis Diagnosis and Risk assessment Initial Management Treatment < Long-Term Management Summary of Treatment Approaches NSTEMI Acute Coronary Syndromes

56 Clinical Outcomes for Patients Stratified by Age (Invasive Vs Conservative Strategies) from TACTICS– TIMI-18 Trial

57 Outcomes According to Degree of Renal Function Impairment in NSTE- ACS Patients in GRACE Registry Special Conditions & Populations chronic Kidney Disease

58 Special Conditions& Populations Diabetes Treatment Effect on 30-day Mortality Among Diabetic Patients with NSTEMI from Six Randomized Clinical Trials

59 Special Conditions& Populations Diabetes

60 Non-ST-segment Elevation Acute Coronary Syndromes Anti-ischemic agents Anti-coagulants UFH or LMWH Factor-Xa inhibitors (Fondaparinux) Direct Thrombin inhibitors (Bivalirudin) Anti-platelet agents ASA Clopidrogel GP IIb/IIIa Inhibitors Revascularization NSTEMI ?

61 Timing of Intervention Few studies have shown superiority of very early intervention vs. deferred intervention ISAR-COOL (small sample size) JAMA 2003 Many trials have shown early hazard with early intervention vs. deferred intervention ICTUS trial NEJM 2005 Mehta meta-analysis JAMA 2005 Grace and Crusade registries Heart 2007, Arch Intern Med 2006 > Timing of intervention recommended on the basis of risk stratification

62 Risk Stratification

63 Summary Management Strategy

64 Summary Long-Term Management

65


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