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Risk stratification and medical management of NSTE-ACS (UA/NSTEMI ) Dr Sajeer K T.

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Presentation on theme: "Risk stratification and medical management of NSTE-ACS (UA/NSTEMI ) Dr Sajeer K T."— Presentation transcript:

1 Risk stratification and medical management of NSTE-ACS (UA/NSTEMI ) Dr Sajeer K T

2 - Plaque rupture or erosion with super imposed non-occlusive thrombus -most common cause of UA/NSTEMI - Plaque rupture or erosion with super imposed non-occlusive thrombus -most common cause of UA/NSTEMI Other mechanism: - dynamic obstruction : spasm of epicardial coronary artery : dysfunction of coronary endothelium - Restenosis : post PCI interventions - Inflammation - Secondary UA: ↑ed O2 demand or ↓ed O2 supply (tachycardia, fever, hypotension, or anemia) Other mechanism: - dynamic obstruction : spasm of epicardial coronary artery : dysfunction of coronary endothelium - Restenosis : post PCI interventions - Inflammation - Secondary UA: ↑ed O2 demand or ↓ed O2 supply (tachycardia, fever, hypotension, or anemia) Pathophysiology

3 Non –occlusive thrombus UA/NSTEMI occlusive thrombus STEMI Stable plaque v/s unstable plaque

4 UA/NSTEMI definition Electrocardiographic ST-segment depression or prominent T- wave inversion and/or positive biomarkers of necrosis (e.g., Troponins) in the absence of ST-segment elevation and in an appropriate clinical setting (chest discomfort or anginal equivalent) - Anderson et al. JACC Vol. 50, No. 7, 2007 ACC/AHA UA/NSTEMI Guideline Revision August 14, 2007:e1–157

5 3 principal presentations of UA  Non–ST-elevation MI - presents as prolonged, more intense rest angina or angina equivalent  Non–ST-elevation MI - presents as prolonged, more intense rest angina or angina equivalent

6 Braunwald Clinical Classification of UA/NSTEMI - Braunwald E: Unstable angina: A classification. Circulation 80:410, 1989.

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8 Rationale for Risk Stratification 1) selection of the site of care: - coronary care unit - monitored step-down unit - outpatient setting 2) selection of therapy: - GP IIb/IIIa inhibitors - invasive management strategy Estimation of the Level of Risk - Focuses on history - Physical findings - ECG findings - Biomarkers of cardiac injury (Cardiac specific Troponin) - TIMI score

9 Clinical Indicators of Increased Risk in UA/NSTEMI

10 Braunwald Clinical Classification of UA/NSTEMI Data from TIMI III Registry: Scirica BM et al: Prognosis in the TIMI III Registry according to the Braunwald unstable angina pectoris classification. Am J Cardiol 90:821, 2002 P= P= 0.001

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12 ECG Indicators of Increased Risk Transient (i.e., <20 minutes) ST elevation, (10% of patients), portends a high risk of future cardiac events

13 Echocardiography RWMA coupled with ECG changes - high risk indicator. Echo identifies other parameters associated with adverse prognosis - LA dilatation - mitral regurgitation - diastolic dysfunction Assessment of LV systolic function, even with Troponin negative status is an important predictor of long term risk. ( class 1 recommendation)

14 Nuclear Cardiac Imaging An abnormal rest myocardial imaging indicates: - high risk of MI - cardiac death - need for revascularization over next 12 months Normal rest myocardial scan: - low risk patients

15 Risk assessment by cardiac Biomarkers Troponins - preferred marker Troponins - preferred marker

16 Troponin I Levels to Predict the Risk of Mortality in Acute Coronary Syndromes

17 Biomarkers contd… Markers of hemodynamic stress: - BNP& NT- proBNP Inflammation: - CRP - Myeloperoxidase - PAPP-A - Soluble CD-40 ligand - IL-6

18 Association between levels of BNP and mortality across the spectrum of acute coronary syndrome in the OPUS-TIMI 16 study.

19 C-Reactive protein (CRP) TIMI 11 A trial : CRP level ≥ 1.55 mg/dL had higher mortality rate, even those patients with negative troponin level (5.8% v/s 0.36%, p= 0.006) Patients with both elevated CRP and Troponin level had highest mortality rates ( 9.1%) FRISC II sub study CRP >10 mg/L : increased risk of cardiac vascular death at all troponin levels.

20 Cardiac markers Clinical Indicators of Increased Risk in UA/NSTEMI

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22 Combined risk assessment scores TIMI PURSUIT GRACE

23 Age ≥ 65 years At least 3 risk factors for CAD Prior coronary stenosis of ≥ 50% ST-segment deviation on ECG presentation( ST deviation >0.5 mm) At least 2 anginal events in prior 24 hours Use of aspirin in prior 7 days Elevated serum cardiac biomarkers 23 Variables Used in the TIMI Risk Score The TIMI risk score is determined by the sum of the presence of the above 7 variables at admission. 1 point is given for each variable. Primary coronary stenosis of 50% or more remained relatively insensitive to missing information and remained a significant predictor of events. - Antman EM, et al. JAMA 2000;284:835–42

24 The TIMI risk score for unstable angina/non–ST elevation MI: A method for prognostication and therapeutic decision- making. JAMA 284:835, 2000.

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27 GRACE registry & GRACE score A global registry of ACS patients from 94 hospitals in 14 countries. GRACE score: Can be used to predict the cumulative risk of death or myocardial infarction in the period from admission to hospital to six months after discharge The tool is simple and applicable to patients across the complete spectrum of acute coronary syndrome

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30 Later Risk Stratification and Management Low-risk patients: - early stress testing is performed ( Exercise ECG -1 st choice non-invasive test) Intermediate risk patients: managed with an early conservative strategy (free of ischemia and heart failure for a minimum of 2 to 3 days ) stress testing Sub maximal protocol Target workload =5 METS, 70 % MPHR or symptom limited

31 Stress echo - in patients with resting STD (≥0.1 mV) - LV hypertrophy - Bundle branch block - Intraventricular conduction defect - Preexcitation, or digoxin. Pharmacologic stress testing with imaging: ( when physical limitations preclude adequate exercise stress ) (e.g., arthritis, amputation, severe peripheral vascular disease, severe chronic obstructive pulmonary disease, or general debility).

32 ACC/AHAA Recommendations for Non-invasive Risk Stratification

33 Medical Management of NSTE-ACS (UA/NSTEMI )

34 Algorithm for management of NSTEACS

35 Anti ischemic therapy and analgesic therapy – Bed rest with continuous ECG monitoring – Supplemental oxygen ( if spo2<90% or respiratory distress). – sublingual nitrate every 5 min for a total of 3 doses. – IV NTG in first 48 hrs ( at the rate of 10 mcg/kg/min ) - persistent ischemia - HF - hypertension class 1

36 Nitrates should not be administered to patients with:  Systolic pressure < 90 mm Hg or ≥ to 30 mm Hg below baseline  Severe bradycardia(< 50 bpm)  Tachycardia (> 100 bpm) in the absence of symptomatic heart failure  Suspected RV infarction.  Who have received a phosphodiesterase

37 Anti ischemic therapy contd.. Oral beta-blocker therapy when hemodynamically stable ( within the 1st 24 h) Contraindications: 1) signs of HF 2) low out put state( SBP<90,oliguria,HR<50) 3) other relative contraindications to beta blockade. (PR > 0.24 s, 2 nd or 3 rd degree AV block, active asthma or reactive airway disease). class 1

38 38 COMMIT Trial ( Lancet 2005;366:1622–32.) - 45,852 patients within 24 h acute MI ― 93% STEMI or LBBB, 7% had NSTEMI - Utility of IV beta blockade followed by oral was tested (Up to 15 mg IV → 50 mg po metoprolol daily v/s placebo) - No decrease of composite primary outcomes ― death, reinfarction, or cardiac arrest - M odest reduction in re- infarctions and VF  Risk of cardiogenic shock especially with initial hemodynamic instability

39 Nondihdropyridine calcium channel blockers - Verapamil - Diltiazem Contraindications for CCBs: Severe LV dysfunction Summary : definitive evidence for a benefit of CCBs in UA/NSTEMI is predominantly limited to symptom control.  DAVIT STUDY - ( Eur Heart J 1984; 5: )  Diltiazem Reinfarction Study - ( N Engl J Med 1986; 315: )

40 ACEI & ARBs ACE inhibitor (orally within 1st 24 h) in patients with - pulmonary congestion - LVEF ≤ 40% contraindications: - hypotension (SBP < 100 mm Hg or < 30mm Hg below baseline) - known contraindications to ACEIs ARBs: if intolerance to ACEI

41 Antiplatelet therapy

42 Aspirin : as soon as possible ( mg) - (non enteric formulation orally or chewed). -Continued indefinitely(75-162mg/d ) in pts who tolerate it. Clopidogrel : - loading dose -300mg - daily maintenance dose 75mg - Continued for at least 1 month and ideally up to 1 year. class 1

43 Four randomized trials showing the benefit of aspirin in UA/NSTEMI, in which the incidence of death or MI was reduced by more than 50% in each of the four trials. The doses of aspirin in the four trials were 325 mg, 1300 mg, 650 mg, and 75 mg daily, indicating no difference in efficacy for aspirin across these doses (Data from Lewis HD, et al: N Engl J Med 309:396, 1983; Cairns JA, et al: N Engl J Med 313:1369, 1985; Theroux P, et al: N Engl J Med 319:1105, 1988; RISC Group: Lancet 349:827, 1990.)

44 Clopidogrel dosage: initial loading dose of 300 to 600 mg clopidogrel is followed by a maintenance dose of 75 mg/day. Initiation with only 75 mg daily will achieve the target level of platelet inhibition after 3 to 5 days. Loading dose of 300 mg will achieve effective platelet inhibition within 4 to 6 hours. Use of a 600-mg loading dose achieves a steady-state level of platelet inhibition after just 2 hours.

45 Benefit of clopidogrel in reducing cardiovascular death, MI, or stroke to 1 year in the CURE trial conducted in patients with UA/NSTEMI and in patients managed medically, with PCI or CABG. The Clopidogrel in Unstable angina to prevent Recurrent ischemic Events [CURE] Trial. Circulation 110:1202, 2004

46 -rapidly acting, more potent thienopyridine. -associated with less respose variability than clopidogrel Dosage : Prasugrel 60 mg should be given promptly and not later than 1 hour after PCI once coronary artery anatomy is defined. Duration and maintenance dose : Prasugrel 10 mg daily Duration : Up to 12 months Contraindications : Elderly ≥ 75 years, Body weight <60 kg Prior history of TIA or stroke PRAUGREL

47 Prasugrel Comparison of efficacy (top) and safety (bottom) in the TRITON–TIMI 38 trial, which compared Prasugrel with clopidogrel in patients with ACS undergoing PCI. Comparison of prasugrel and clopidogrel on the development of stent thrombosis. ARC = Academic Research Consortium. TRITON TIMII 38 Trial

48 GPIIb/IIIa Inhibitor Upstream strategy: Eptifibatide or tirofiban is administered in the ED or hospital for medical stabilization usually in an anticipation for an early invasive approach. Adjunctive strategy: Use either Eptifibatide or Abciximab as adjunctive therapy immediately before PCI

49 The routine upstream administration of GP IIb/IIIa inhibitors did not improve the primary outcome of death or myocardial infarction (MI) at 30 days and significantly increased bleeding. EARLY ACS trial ( in 9492 pts with UA/NATEMI) Upstream glycoprotein (GP) IIb/IIIa inhibitor V/S Adjunctive strategy GP IIb/IIIa inhibitor

50 Anti coagulant therapy recommendations Class I Conservative strategy: - UFH or Enoxaparin - Fondaparinux ( preferable in pts with increased risk of bleeding) Enoxaparin or fondaparinux preferable to UFH unless CABG is planned with in 24 hrs Class IIa Invasive strategy: - UFH - Enoxaparin - Bivalirudin

51 Unfractionated heparin (UFH) - ACC/AHA Guidelines recommend weight adjusted dose : 60 units/kg bolus (maximum 4000 u) : 12 units/kg/hr infusion (1000 units/hour). - Most of trials continued therapy for 2 to 5 days. - (Optimal duration of anticoagulation remain undefined.)

52 Systematic overview of death/MI at 30 days including patients enrolled in six trials comparing enoxaparin with UFH. Overall, a significant reduction in death or MI was observed (10.1% vs 11.0%) ( Petersen JL, et al. Efficacy and bleeding complications among patients randomized to enoxaparin or unfractionated heparin for antithrombin therapy Non STE ACS: a systematic overview. JAMA 2004;292:89, 96) UFH v/s Enoxaparin

53 Fondaparinux OASIS- 5 trial: The rate of major bleeding was reduced significantly— almost by half—in the fondaparinux arm (Fondaparinux arm 2.2%) versus (4.1% enoxaparin arm). In patients undergoing PCI, fondaparinux has associated with more than a 3 fold increased risk of catheter-related thrombi. It is recommended only in patients at a higher risk of bleeding who are managed conservatively

54 Bivalirudin. Composite ischemia end point at 30d Ischemia end point by clopidogrel loading before PCI at 30d Ischemia end point by clopidogrel loading before PCI at 30d Ischemia end point by No clopidogrel loading before PCI at 30d Ischemia end point by No clopidogrel loading before PCI at 30d Major bleeding at 30 days ACUITY TRIAL Bivalirudin alone UFH+ GPIIb/IIa Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial was a complex trial performed in 13,819 patients with UA/NSTEMI, all of whom underwent cardiac catheterization within 72 hours

55 Treatment strategies and interventions 1. Early invasive strategy: Routine CAG PCI, CABG, Medical Mx 2. Conservative approach: Medical Mx Recurrent Ischemia (at rest /on noninvasive stress test) Revasularization

56 High risk clinical events  Recurrent angina/ischemia at rest with low-level activities despite intensive medical therapy  Elevated cardiac TnT or TnI  New/presumably new ST- segment depression  Signs/symptoms of heart failure or new/worsening mitral regurgitation  High-risk findings from noninvasive testing  Hemodynamic instability  Sustained ventricular tachycardia  PCI within 6 months  Prior CABG  High risk score (e.g., TIMI, GRACE)  - LVEF < 40%)

57 Meta-analysis of the benefit of a routine invasive versus “selective” invasive (i.e., conservative) strategy for patients with unstable angina or NSTEMI on the rate of death, myocardial infarction, or rehospitalisation through follow-up. J Am Coll Cardiol 2006; 48:1319.

58 Medical therapy BMS group DES group ASA mg/d indefinitely & Clopidogrel 75 mg/d for at least 1 month and ideally up to 1 year ASA mg/d (1 month) ↓ mg/d (indefinitely) & Clopidogrel 75 mg/d or Prasugrel 10 mg/d (for at least 1 year) ASA mg/d (SES-3months) (PES-6months) ↓ mg/d (indefinitely) & Clopidogrel 75 mg/d Or prasugrel 10mg for at least 1 year Long term Antiplatelet therapy Class I

59 Lipid Management Lipid management should include assessment of a fasting lipid profile for all patients, within 24 h of hospitalization. High dose statins in the absence of contraindications, regardless of baseline LDL-C and diet modification, should be given to post-UA/NSTEMI patients, including post revascularization patients. LDL goal: <100mg/dl <70 mg/dl reasonable (classIIa)

60 Meta analysis of intensive v/s standard statin therapy, showing a highly significant 16% reduction in the risk of coronary death or MI (p<0.0001)

61 The benefit of intensive statin therapy initiated early after acute coronary syndrome (ACS) in the PROVE IT–TIMI 22 trial. A significant reduction in events is seen in the first 30 days. J Am Coll Cardiol 46:1405, 2005.)

62 Patients with UA/NSTEMI Aspirin, clopidogrel, UFH/enoxaparin, beta blocker, nitrates. High risk +Troponin, ST▲’s, TIMI score≥3 Recurrent Ischemia, CHF, Prior Revascularization Low risk Normal ECG Negative Markers TIMI score 0- 2 GpIIb/IIIa inhibitor Conservative strategy Invasive strategy summary

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