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NSTEMI AND ANTITHOMBOTICS 1

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  • Some basics, some reviews, some new.
    Review of litterature backing up what we do
    All based on Sept 2000 AHA-ACC recommendations on UA and NTSEMI with addition of last year trials and practical points.
  • Backbone of my lecture
    www.acc.org
  • Various progression of acute coronary syndrome
  • 25% progress to Q-wave MI ie transmural infarction
  • Combination of 5 components leading to myocardial ischemia
    Mechanical + dynamic obstruction, inflammation, acute thrombosis and incr demand
    Most common UA: atherosclerosis and unstable plaque (60 + 30%)
    Printzmetal angina: atheroscledoris and vasospasm (30 + 60%)
  • Clinical markers fro high-intermediate-low risk for UA patient
    Dated 1994
    No clinical correlation
    Still in 2000 guideline
    Age>70
    Biphasic + troponin level
    High risk = real positivity
  • Biphasic T waves in leads V2 and V3 or symmetric, often deeply inverted T waves in leads V2 and V3.
  • Troponin essay are antibody against specific part of the troponin molecule
  • Relationship of troponin to mortality.
    Same for troponin T
    ?high trop normal CKs
    Ck still gold standard for early reinfarction
    Use trop I at the RVH and trop T at the MGH
  • Normal, abnormal, high (0.01-0.099-0.1)
  • Lancet editorial of this week says the same thing…
  • Clear difference between true Mi and only UA but since clinically a continuum + potential difficulty at “educating” the MDs.
  • 41 yo woman, 3 days post liposuction
  • You diagnosed it, ltes treat it
    Management of UA/NSTEMI
    Let’s walk through it…
    Nothing new
    Oxygen: only if sign of cyanosis or O2 sat below 90%
  • Diltiazem if B-blocker contraindicated + no depressed LV function
    ACEi if -hypertensive despite nitrate/b-blocker in the face of CHF –depressed systolic function
    -diabetes
    All level B or C evidence.
    CCB after maxed out on nitrates and b-Blockers
    IABp for sevre ongoing or recurrent ischemia despite maximal medical management.
    Long acting Nondihydropyridne instead of b-BLOCKERS
    Dihydropyridine : Nefidipine, amlodipine.
  • No evidence to back inclusion of high risk features.
  • 4 modes of action
    B-blocker to prevent incr HR thereby incr MVO2
    Use unless contraindication (viagra)
    Ceiling of 200u/min (300-400 X 3-4 weeks have not incr methg)
    ISSIS-4 Gissi-3 failed to show improved survival.
  • No RCT
    Endothelin-1 causes platelets activation
    EP-1 which degrades endothelin 1 concentration (2.5 – 1.7 products) (2.5), (0.8 –1.3 by-products) (0.9)
    68 QwMI and 29 volunteers
  • No study to back iv vs po form
  • No good trial, just expert opinion
  • Great drug! But…
  • Adalat and norvasc
    Short acting adalat only when appropriatly B-blocked
    Danish study group on verapamil in Myocardial infarction
    Holland interuniversity nifedipine/metoprolol trial
    Good if already on B-blocker
  • Plavix and ticlid
  • Needs ISIS-2 study; 1988 ASA or streptokinase or both or neither
  • Primary outcome:MI, stroke, death
    Second number: Primary outcome + refractory ischemia
    After 3000 pts, switch from (no ST change or + hx of CAD) to (+ st changes or + markers)
    Not in McGill due to Gp2b3a + angio available… answer from all the cardiologists I asked to
  • Theroux used fixed dose heparin,
    ASA did not had anything more except risk of bleeding
    460 pts
  • F2 (thrombin is most important) but f10 also is necessary
    Prediction is what is important
  • Pentasaccharide binds to antithrombin, needs >18 saccharides to inactivate thrombin
  • Dalteparin (Fragmin): nonsignifcant incr end point at day 6 but subgroup analysis showed decr mortality at 6 days (6% vs 2.5%) and 40 days (14.2 vs 7.4%) in trop positive patients.
    Essence: enoxaparin (lovenox): 16.6% vs 19.8% at 14 days but non-weight adjusted UFH
    only 46% properly anticoagulated at 24hr.
    TIMI 11B: iv bolus LMWH + sc, MI-death at 8 days non-significant (6.9 to 5.7%)
    ST changes or + markers after first 700 pts (hx of CAD and CP was initially included.
    Composite end-point (14.5 to 12.5%) in 3910 pts
  • Resume of antithrombotics trials: can notice decreasing effects of added therapy on overall risk ratio.
    ASA vs placebo
    Addition of heparin
    Addition og GPIIb/IIIa
  • Conflicting results between Gusto2b and Timi9b
  • Prevents progression of white clot to red clots by preventing platelets aggregation through fibrinogen to form thrombus
  • Composite end points
  • Very good numbers for PCI and hard to dispute but irrelevant to ER
    Focus is on prism-plus and pursuit
    Overall 2% absolute decrease death or MI
  • 3200 pts
    On average, PTT was around 80
  • Subgroup analysis showing good for + markers
    Same for trop T
    Independent of revascularization procedures (PCI or CABG)
    Heparin with + trop do worst (on right)
  • 1900 pts
    Composite end-point:MI, death, refractory ischemia
    Non-weight based heparin
    NNT: 20 to 25
  • 22 end-points: 3 strong <0.01, 8 weaker 0.01 to 0.05
  • Major bleed: 5 gr of Hgb
    Cath rate:
    North America 79%
    Western Europe 58%
    Eastern Europe 20%
  • GP2b/3a if no cath lab???
  • Not proof that everything is time dependent as in thrombolysis
  • Risk factors for CAD: HTN, diabetes, current smoker, family hx of CAD, hypercholesterolemia
    Coronary stenosis: still valid model if do not know the answer
    Severe anginal symptoms: 2 or more episodes within 24 hrs
    CKMD or troponin
  • People (some cardiologist) want o use GP 2b/3a inh when score is 5 or above
  • Subgroup analysis of UFH vs LMW heparin; different slope
  • Level 5 since database group was comparing UFH to LMW heparin…
  • Personnalize TIMI risk program
    Do it slowly
  • Considering side-effects…
  • From international group
    ECG changes or hx of CAD (no markers)
    Fairly good but not perfect: B-blocker 40% miss, 15% decr mortality = 6% gain
    Nitrates is highlighted because if CP + heparin + nitro = GP2b/3a inh
  • TACTICS: 97% cath vs 51% cath = 520 extra pts got cath
    CEP: death, MI, readmission for ACS within 6 months
  • 11% at 6 months
  • 1 nothing
    2 stented
    3 stent or CABG
    4 CABG
  • Just to let you know
  • Is it really justify???
  • ? Definition of UA vs NSTEMI
  • Cocaine coronary blood flow: from 140 to 120 (down to 100 with propranolol)
  • Transcript

    • 1. NSTEMI and antithrombotics Dr. Gilbert Boucher R4 Emergency Medicine McGill
    • 2. Goals • Review definitions of Non-ST-elevation Myocardial infraction and related items. • Prognostic factors. • Current therapies. • Special cases.
    • 3. What's New? October 4 , 2001 Practice Guidelines: Atherosclerotic Cardiovascular Disease September 1 , 2001 Practice Guidelines: Atrial Fibrillation April 27 , 2001 Practice Guidelines: Percutaneous Coronary Intervention April 27 , 2001 Expert Consensus Document: Catheterization Laboratory Standard April 3 , 2001 Consensus Conference Report: Care of the Patient with Adult Congenital Heart Disease April 2 , 2001 Expert Consensus Document: Standards for Acquisition, Measurement and Reporting of Intravascular Ultrasound Studies March 1, 2001 Teaching Slides: ACC/AHA Guidelines for the Management of Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction January 1, 2001 Consensus Conference Report: Mechanical Cardiac Support 2000: Current Applications and Future Trial Design November 1, 2000 Clinical Competence Statement: Invasive Electrophysiology Studies, Catheter Ablation, and Cardioversion October 1, 2000 Clinical Competence Statement: Stress Testing September 1, 2000 Practice Guidelines: Management of Patients with Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction September 1, 2000 Consensus Conference Report: Myocardial Infarction Redefined—A Consensus Document of the Joint European Society of Cardiology/American College of Cardiology Committee for the Redefinition of Myocardial Infarction July 1, 2000 Expert Consensus Document: Electron-Beam Computed Tomography for the Diagnosis and Prognosis of Coronary Artery Disease June 1, 2000 Training Statement: Adult Cardiovascular Medicine (COCATS) Revised 6/00 Task Force #5: Training in Nuclear www.acc.org
    • 4. ACUTE CORONARY SYNDROMEACUTE CORONARY SYNDROME No ST ElevationNo ST Elevation ST ElevationST ElevationST ElevationST Elevation Unstable Angina NQMI QwMI Myocardial Infarction NSTEMI
    • 5. Myocardial infarction: acute, evolving, recent Typical rise and gradual fall (troponin) or more rapid rise and fall (CK-MB) of biochemical markers of myocardial necrosis with at least one of the following: – a) ischemic symptoms; – b) development of pathologic Q waves on the ECG; – c) ECG changes indicative of ischemia (ST segment elevation or depression); or – d) coronary artery intervention (e.g., coronary angio- plasty).
    • 6. ACC/AHA Guidelines • NSTEMI is an acute process of myocardial ischemia with sufficient severity and duration to result in myocardial necrosis. • The initial ECG in patients with NSTEMI does not show ST-segment elevation. • NSTEMI is distinguished from UA by the detection of cardiac markers indicative of myocardial necrosis in NSTEMI and the absence of abnormal elevation of such biomarkers in patients with UA. Definition: NSTEMIDefinition: NSTEMI
    • 7. Definition: unstable angina • Unstable angina—an acute process of myocardial ischemia that is not of sufficient severity and duration to result in myocardial necrosis. – Do not release biomarkers indicative of myocardial necrosis into the blood.
    • 8. UA/NSTEMI 3 PRESENTATIONS Rest Angina* Angina occurring at rest and prolonged, usually > 20 minutes New-onset Angina New-onset angina of at least CCS Class III severity Increasing Angina Previously diagnosed angina that has become distinctly more frequent, longer in duration, or lower in threshold (i.e., increased by > 1 CCS)class to at least CCS Class III severity. * Pts with NSTEMI usually present with angina at rest. Braunwald Circulation 80:410; 1989
    • 9. CAUSES OF UA/NSTEMI Thrombosis Thrombosis Mechanical Obstruction Mechanical Obstruction Dynamic Obstruction Dynamic Obstruction Inflammation/ Infection Inflammation/ Infection  MVO2  MVO2 Braunwald, Circulation 98:2219, 1998 . .
    • 10. Wellens’ syndrome
    • 11. The simplified criteria for Wellens' syndrome are as follows: Prior history of chest pain Little or no cardiac enzyme elevation No pathologic precordial Q waves Little or no ST-segment elevation No loss of precordial R waves Biphasic T waves in leads V2 and V3 or symmetric, often deeply inverted T waves in leads V2 and V3 . Wellens' criteria are quite specific for left anterior descending artery disease. All of the patients (n=180) in his 1988 study had more than 50% narrowing of the left anterior descending artery (mean=85% narrowing) with complete or near-complete occlusion in 59%.
    • 12. Troponins • I vs T… – Troponin I does not accumulate in renal failure – Different assays of same troponin have different values due to different isotopes of antibodies • Very sensitive – Estimate that 30% of patients with U/A are now diagnosed with NSTEMI due to elevated troponins • High correlation with death, being primary cardiac or not…
    • 13. N Engl J Med 1996;335:1342–9.
    • 14. Troponemia • Clin Chem 2000 46: 650-657. – 46 pts with septic shock – 36-50% had + trops – 12 pts nonsurvivors: negative autopsy for necrosis – Associated with severe LV dysfunction. • Clin Chem 2001 47: 412-417 – 244 pts, chronic hemodialysis, troponin T – Higher trops or increasing trops associated with death. • 6%, 43%, and 59% total death. • in 0%, 14%, and 24% cardiac death
    • 15. Troponitis… • Clin Chem 1999:National Academy of Clinical Biochemistry Standards of Laboratory Practice: Recommendations for the Use of Cardiac Markers in Coronary Artery Diseases • Troponin I can be falsely elevated due to fibrin clot, heterophilic antibodies. • Use of 2 cut-offs point would require too much physician education… – AHA needs to better define NSTEMI due to important implication of being diagnosed with MI.
    • 16. Figure 1. Plot of the appearance of cardiac markers in blood vs time after onset of symptoms. Peak A, early release of myoglobin or CK-MB isoforms after AMI; peak B, cardiac troponin after AMI; peak C, CK-MB after AMI; peak D, cardiac troponin after unstable angina. Data are plotted on a relative scale, where 1.0 is set at the AMI cutoff concentration.
    • 17. Other markers • Delta values at 2 hours could proved to be very sensitive. – 2 hour delta CK-MB 88% sens vs delta trop I 61% • Specificity of 96% • ?early marker for more aggressive treatment Am J Emerg Med - 2000 Jan • CRP: JACC 1998 Jun out of TIMI-11a – Neg trop but pos CRP = 5.8% death – Neg trop and neg CRP = 0.36% death – Pos trop and CRP = 9.1% death
    • 18. Recommended • Class I: – Aspirin, Nitrate, B-blockers, morphine, O2 (prn). – Nondihydropyridine (cardizem/verapamil). – ACEi for specifics. • Class 2a: – ACEi for all. – Long-acting CCB for recurrent ischemia. – IABP if all fails. • Class 2b: – Extended form of Nondihydropyridine. – Short acting dihydropyridine in the presence of B-
    • 19. Oxygen • For: – Cyanosis – Resp distress – High risk features • Consume resources • Evidence is lacking.
    • 20. Nitrates: Decr MVO2, incr coronaries oxygenation Actions – Dilate venous bed: decr preload and ventricular wall tension. – Smaller dilatation of arterial system: decr afterload and ventricular wall tension. • Need B-blocker – Dilatation of atherosclerotic coronaries – Decreased platelets adhesiveness. • For – ischemia despite nitro X 3 and iv B-blockade – high-risk patients (non-hypotensive). • Prethrombolytics: 35% mortality reduction.
    • 21. Morphine • Potent anxiolytic and analgesic action • Potentially beneficial – Venous dilatation – Decr HR – Decr sBP (Decr MVO2) – Activates neutral endopeptidases • Ann Emerg Med. May 2001;37:445-449. • Nausea and vomiting in 20% • Hypotension • Meperidine if allergic
    • 22. Beta-blockers • Decr sBP • Decr SA node rate, contractility, AV node conduction. • Incr diastole filling time. • iv form for high-risk pts/on going pain. • Oral for intermediate/low risks patients. • No preferred agents except better if B-blocker without ISA (metoprolol, atenolol, propramolol, esmolol).
    • 23. B-blockers • Contraindications (consensus): – 1st degre AV block >24 msec – 2nd or 3rd degre AV block without pacemaker – Asthma – Severe LV dysfunction with CHF • Caution with: – COPD – Bradycardia <50 – Hypotension <90 • Goal is bpm of 50-60 unless side-effects
    • 24. B-blockers • 13% reduction of progression of UA to AMI. • Extrapolate data from use in AMI, recent MI, stable angina, heart failure.
    • 25. Calcium channel blockers • Inhibit vasculature SM contracture – Coronary vasodilatation • Inhibit myocardial muscle contraction • AV block • Slow sinus node
    • 26. Calcium channel blockers • Dihydropyridines: nifedipine and amlodipine – peripheral vasodilatation • Verapamil: DAVIT study (3200 pts) – Only favorable trend • Nifedipine: HINT study (500 pts) – Incr MI by 16%, decr by 20% if with metoprolol – But… metoprolol alone decr by 24%!!! • Diltiazem showed trends of improved outcome – CKMB level, reinfarction rate – Same mortality • … except in LV dysfunction ACS
    • 27. Calcium channel blockers • Conclusion: – Good symptom reliever – Trend of improved outcome with non- dihydropyridine agents • To use if unable to use B-blockers
    • 28. Antiplatelet agents • Aspirin ASAP! – Thienopyridine (clopidogrel or ticlopidine) if hypersensitivity of major GI intolerance
    • 29. Aspirin • Cyclooxygenase-1 inhibitor – Prevents thromboxane A2 formation • Dosing: 160 mg or 325 mg – Based on ISIS-2 which definetly established its efficacy. • Can use pr route.
    • 30. Adenosine diphosphate inhibitors • Clopidogrel acts faster than ticlopidine. • Ticlodipine: Gi se, neutropenia, TTP • Clopidogrel: minimal rash and diarrhea – 11 TTP within 14 days (3 millions pts) • CURE study: NEJM Aug 2001 – 12000 pts, plavix 300mg po – 9.3 vs 11.4, 16.5 vs 18.8 – ST changes or + markers – No GP2b3a inh or angio
    • 31. Plavix: Safety if angio or used with Gp2b3A inh • Lancet August 2001: PCI-CURE study • 2600 pts. • Plavix 300mg loading • No increased bleeding problem whether plavix +/- GPIIb/IIIa inh were used. • Better outcome before an after PCI.
    • 32. Other po agents • Sulfinpyrazone • Dipyridamole • Prostacyclin • Oral GP IIB/IIIA inhibitor: – 4 studies: 1 PCI, 3 NSTEMI • 2 increased mortality • None presently recommended
    • 33. Anticoagulants • UFH • LMW heparin • Hirudin
    • 34. UFH • Activates antithrombin III – Inactives thrombin (f2), f9a and f10a • Molecular weight: 5 000 to 30 000 D • Binds to various proteins, cells , endothelium • Unpredictable. – Weight adjusted dosage • Incr need in DM and smoking, lower with age • Theroux et al. N Engl J Med 1988;319:1105– 11. – MI rate of 12% down to 0.8% in UA
    • 35. LMW heparin • Molecular weight of 4200 to 6000 D • Factor Xa to thrombin inhibition ratio of 1.9 to 3.8 • Only 25-50% have >18 saccharides – both f2 and 10 inhibition – Rest inhibits only factor Xa
    • 36. LMW heparin: ? better
    • 37. Also… • Can only reverse about 60% of anticoagulation with protamine • Increase rate of minor bleeding (9.1% vs 2.5%) • Cannot monitor ACT during PCI, needs to stop 12 hours pre CABG. • Not for renal failure patients (GFR<30cc/min) • Decreased incidence of HIT. • >100kg: ?maximum of dosing vs study dosing – Enoxaparin 100mg sc bid vs weight all the way as in TIMI 11B
    • 38. But going to cath lab… • Start UFH without bolus 6 hours after last dose. • If go to cath lab, consider pt fully anticoagulated when giving heparin boluses – unable to monitor. • If on UFH, wait 1 hour then give LMW heparin dose.
    • 39. Hirudin • Direct thrombin inhibtor. • For patients with HIT or history of. • Binds directly to catalytic site of thrombin without going through antithrombin III • TIMI 7: better than ASA alone in UA… • Mild improvement compared to UFH but increase in bleeding, no benefit in STEMI. • Meta-analysis shows OR of 0.90
    • 40. Platelet GP IIb/IIIa Receptor Antagonists • Activation of platelets leads to configurational change increasing affinity for fibrin and other ligands • Necessary final step to platelets aggregation. • Needs 80% blockade to achieve potent antithrombotic effects
    • 41. GP IIb/IIIa Receptor Antagonists. • Abciximab (reopro): non-specific binding – Unclear significance • Eptifibatide (integrilin), tirofiban (aggrastat): very specific binding achieve >80% within 5 minutes • Different antagonists can bind at different sites and can paradoxically activates the GPIIb/IIIa receptor – ?what is happening with the oral form.
    • 42. GP IIb/IIIa Receptor Antagonists • 4 main studies • 2 positives • High-risk features • 11.7% vs 8.7%, • 15.7% vs 14.2%
    • 43. Numbers… • PRISM:Platelet Receptor Inhibition in Ischemic Syndrome Management. – heparin (non-weight based) vs tiroban X 48hrs ECG changes or enzymes or very strong hx of CAD Composite end-point better at 48hr but only trend at 30 days. MI/death: non-significant at 48 hrs but + at 30 days (3.6 vs 2.3%).
    • 44. PRISM: Lancet 1999 • Figure 1: Adjusted hazard ratios (95% CI) for treatment with tirofiban by troponin I quartiles • Figure 2: Event-rate curves (mortality, myocardial infarction) for 30-day follow- up for patients with + troponin
    • 45. Numbers… • Prism-plus: Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms • THE study • ST changes or + enzymes • Tiroban alone dropped due to too much mortality – 4.6% vs 1.1 and 1.5%??? (remember PRISM study) • At 7 days, composite end-point: 17.9% vs 12.9% • 22% CEP reduction at 30 days (absolute 3.8%)
    • 46. Numbers… • PURSUIT: Eptifibatide – Platelet Glycoprotein IIb/IIIa in Unstable Angina:Receptor Suppression Using Integrilin Therapy. – 11 000 pts – + ECG changes or enzymes rise • Death or MI at 30 days: 15.7% vs 14.2% – 9.1% vs 7.6% at 4 days – 11.6% vs 10.1% at 7 days – Major bleed increased by 1.5% • Cath rate overall: 60%
    • 47. Real Numbers! • GUSTO IV:Lancet June 2001 • Abciximab: 7800 pts without PCI • Same mortality at 30 days: 8-9% – Despite all sorts of subgroup analysis…
    • 48. Antithrombotics: 1, 2 or 3 agents??? •  
    • 49. Cardiogenic shock… BAD!!! • Circulation 1999: GUSTO IIb • 200 pts with NSTEMI and shock – Incidence of 2.5% • 73% mortality • But median time to shock 76 hrs… – 9.6 hrs in STEMI
    • 50. Last words: • Journal of Emergency Medicine October 2000: – “The effect of early ED treatment with GPIIb/IIIa inhibitors has never been formally studied until now”. – EARLY trial will compare early ED, vs late CCU vs catheterization laboratory
    • 51. TIMI score • JAMA, August 16, 2000 • Databases of ESSENCE and TIMI11B • 12 variables, 7 significants – Age > 65yo – 3 risk factors for CAD – Prior coronary stenosis of > 50% – St deviation – Severe angina symptoms – ASA use within 7 days – Elevated serum cardiac markers
    • 52. Figure 1. TIMI Risk Score   Rates of all-cause mortality, myocardial infarction, and severe recurrent ischemia prompting urgent  revascularization through 14 days after randomization were calculated for various patient subgroups based on  the number of risk factors present in the test cohort (the unfractionated heparin group in the Thrombolysis in  Myocardial Infarction [TIMI] 11B trial; n = 1957) (see Table 1). Event rates increased significantly as the TIMI risk  score increased (P<.001 by     2  for trend). •GP IIb/IIIa inh for score 5 or above???
    • 53. Figure 2. Validation of TIMI Risk Score and Assessment of Treatment Effect According to Score   Rates of all-cause mortality, myocardial infarction, and severe recurrent ischemia prompting urgent revascularization through 14 days  after randomization were calculated for the enoxaparin and unfractionated heparin groups in the Thrombolysis in Myocardial Infarction  (TIMI) 11B trial and the Efficacy and Safety of Subcutaneous Enoxaparin in Unstable Angina and Non-Q-Wave MI trial (ESSENCE),  based on the TIMI risk score. The pattern of increasing event rates with increasing TIMI risk score was confirmed in all 3 validation  cohorts (P<.001 by     2  for trend). C statistics were 0.65 for the unfractionated heparin group and 0.61 for the enoxaparin group in TIMI  11B; and 0.65 for the unfractionated heparin group and 0.59 for the enoxaparin group in ESSENCE. The rate of increase in events as  more risk factors were present was significantly lower in the enoxaparin group in both studies (for TIMI 11B, P = .01; for ESSENCE, P = . 03). Positive values for absolute risk difference (ARD) and number needed to treat to prevent 1 event (NNT) indicate calculations favoring  enoxaparin, while negative values indicate calculations favoring unfractionated heparin.
    • 54. As Dr. Lang would said… • Auto-validation on its own cohort • Retrospective • Specific (but large) group • That would make it a level…4 if we want to use  it as a Clinical decision rule to know whether or  not to use GP IIb/IIIa inhibitors.               
    • 55. TIMI Risk Calculator For Unstable Angina In the blue column, please enter the patient's age, and then answer each clinical question with a Y (for yes) or an N (for no). The patient's risk appears at the bottom of the blue column.  TIMI Risk Score for UA/NSTEMI Entry Score Age   1 History of Hypertension (Y or N)   0 History of Diabetes (Y or N)   0 Current Smoker (Y or N)   0 Hypercholesterolemia (Y or N)   0 Family history of Coronary Artery Disease (Y or N)   0 Prior angiographic stenosis >50% (Y or N)   0 Severe anginal symptoms (>= 2 episodes rest pain in past 24 hrs) (Y or N)   0 Use of aspirin within the last 7 days (Y or N)   0 Elevated cardiac markers (either CKMB or cardiac troponin) (Y or N)   0 ST deviation (horizontal ST depression or transient ST elevation >= 1 mm) (Y or N)   0 Total Risk Score (0-7) 1 Risk of Death/MI/Urgent Revascularization by 14 Days (%) 4.70%
    • 56. Cost $$$$ • Tiroban: 950$/3 days • Abciximab: 2000$/treatment – But how come we are almost never using  streptokinase anymore… are we  reasonable???
    • 57.     What about: Plavix vs  GP IIb/IIIa? 18.8% vs 16.5% 17.9 vs 12.9% JUST a thought …
    • 58. But back to standard of care… The classics: How do we do? • In-hospital drugs treatment (%), 1998                                       USA         Canada  World Intravenous heparin  79  88 73 Aspirin  91  92  92 B-blockers  57  73  63 Calcium antagonists  59  53  53 Intravenous nitrates  68  40 51
    • 59. Angio: stat or later • TACTICS: N Engl J Med 2001; 344:1879-1887, Jun  21, 2001 2220 patients, within 48 hours vs selectively all got ASA, heparin, GPIIb/IIIa inh 15.9% vs 19.4% at 6 months 6% more CABG, 520 extra caths/1100 pts MI: 4.8% vs 6.9% • Pre GPIIb/IIIa inhibitors: TIMI3b (1995) • Early 18.1% vs 16.2% late • Decr length of stay • VANQWISH Investigators: 920 pts • Early 7.8% vs 3.3% late at hospital discharge
    • 60. More does not equal better • Lancet 1998; 352: 507–14 • 8 000 pts, various countries (Brazil, USA,  Canada, Australia, Hungary, Poland) – 59% vs 21% angio rate – Same overall MI/death rate: 4.7% at 7 days • Late angio: decreased rate of overall  cardiovascular event (including stroke) despite  higher recurrent angina
    • 61. What do we find anyway on  angio… • Typically shows the following profile: – 1) no severe epicardial stenosis in 10% to 20% – 2) 1-vessel stenosis in 30% to 35% – 3) multivessel stenosis in 40% to 50% – 4) significant (.50%) left main stenosis in 4% to 10%.
    • 62. Next: early statin???!!!… • Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) • JAMA April 2001 • 2000 pts • Atorvastatin 80mg/d between 24 and 96hrs of  admission. • 17.4% vs 14.8% at 4 months, mostly recurrent  symptomatic ischemia requiring rehospitalization.
    • 63. Risk stratification Noninvasive stress testing in low- risk patients who have been free of ischemia at rest or with low-level activity and of CHF for a minimum of 12 to 24 h. (Level of Evidence: C)
    • 64. Risk stratification • Stress test only if free of: – ST-segment abnormalities – bundle-branch block – LV hypertrophy – Intraventricular conduction defect – Paced rhythm – Preexcitation – Digoxin effect. Otherwise need imaging: echo or
    • 65. Special groups • Women: more atypical symptoms – ?better outcome in UA then men • Elderly: More disease • Diabetics: Increased risk for any ACS • Post-CABG: low threshold angio • All same protocols and numbers…
    • 66. Cocaine users • Coronary vasospasms – Worsen by minimal atherosclerosis – Reversed by CCB – ST-changes in 38% of pts in detox centers • Detoxify by cholinesterase in liver and plasma – Less available in infants or elderly • Increased platelets sensibility • Decrease antithrombin III and protein C
    • 67. Cocaine users as per AHA • NTG and CCB for ST changes • Angio if persistent ST elevation or if  thrombus found – Thrombolysis if not available • B-blockers if sBp > 150 or HR > 100 – Labetolol preferred
    • 68. B-blockers for cocaine  users??? Annals of Internal Medicine. Jun 1990  30 volunteers • In cath lab • Cocaine followed by propranolol • No change in Hr or BP but: – 50% incr in coronary resistance with 20% decr in flow No mention of benzos???????
    • 69. Conclusion • Troponemia is a bad sign. • Lots of studies/numbers out there • Stratification is probably the way to go to  target selected population but can we  rely on present evidences…
    • 70. Questions?