Presentation on theme: "Risk stratification and medical management of NSTE-ACS (UA/NSTEMI )"— 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 Pathophysiology- Plaque rupture or erosion with super imposed non-occlusive thrombus-most common cause of UA/NSTEMIOther mechanism:- dynamic obstruction: spasm of epicardial coronary artery: dysfunction of coronaryendothelium- Restenosis : post PCI interventions- Inflammation- Secondary UA:↑ed O2 demand or ↓ed O2 supply(tachycardia, fever, hypotension, oranemia)
4 UA/NSTEMI definitionElectrocardiographic ST-segment depression or prominent T-wave inversionand/or positive biomarkers of necrosis (e.g., Troponins)in the absence of ST-segment elevationand 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 intenserest angina or angina equivalent
6 Braunwald Clinical Classification of UA/NSTEMI Braunwald E: Unstable angina: A classification. Circulation 80:410, 1989.
8 Rationale for Risk Stratification 1) selection of the site of care:- coronary care unit- monitored step-down unit- outpatient setting2) selection of therapy:- GP IIb/IIIa inhibitors- invasive management strategyEstimation 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 P= 0.057P= 0.001Data 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
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 adverseprognosis- LA dilatation- mitral regurgitation- diastolic dysfunctionAssessment of LV systolic function, even with Troponin negativestatus is an important predictor of long term risk.( class 1 recommendation)
14 Nuclear Cardiac Imaging An abnormal rest myocardial imagingindicates:- high risk of MI- cardiac death- need for revascularization over next 12 monthsNormal rest myocardial scan:- low risk patients
15 Risk assessment by cardiac Biomarkers Troponins - preferred marker
16 Troponin I Levels to Predict the Risk of Mortality in Acute Coronary Syndromes
17 Markers of hemodynamic stress: Biomarkers contd…Markers of hemodynamic stress:Inflammation:- CRP- Myeloperoxidase- PAPP-A- Soluble CD-40 ligand- IL-6- BNP& NT- proBNP
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= )Patients with both elevated CRP and Troponin levelhad highest mortality rates ( 9.1%)Topol hand bookFRISC II sub studyCRP >10 mg/L : increased risk of cardiac vasculardeath at all troponin levels.
20 Cardiac markers Clinical Indicators of Increased Risk in UA/NSTEMI
23 Variables Used in the TIMI Risk Score Age ≥ 65 yearsAt least 3 risk factors for CADPrior coronary stenosis of ≥ 50%ST-segment deviation on ECG presentation( ST deviation >0.5 mm)At least 2 anginal events in prior 24 hoursUse of aspirin in prior 7 daysElevated serum cardiac biomarkersThe 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.
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 ormyocardial infarction in the period from admission tohospital to six months after dischargeThe tool is simple and applicable to patients across the complete spectrum of acute coronary syndrome
30 Later Risk Stratification and Management Low-risk patients:- early stress testing is performed( Exercise ECG -1st 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 testingSub maximal protocolTarget workload =5 METS, 70 % MPHR or symptom limited
31 - in patients with resting STD (≥0.1 mV) - LV hypertrophy 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
35 Anti ischemic therapy and analgesic therapy Bed rest with continuous ECG monitoringSupplemental 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- hypertensionclass 1
36 Nitrates should not be administered to patients with: Systolic pressure < 90 mm Hg or ≥ to 30 mm Hgbelow baselineSevere bradycardia(< 50 bpm)Tachycardia (> 100 bpm) in the absence ofsymptomatic heart failureSuspected RV infarction.Who have received a phosphodiesterase
37 Anti ischemic therapy contd.. class 1Oral beta-blocker therapy when hemodynamicallystable ( within the 1st 24 h)Contraindications:1) signs of HF2) low out put state( SBP<90,oliguria,HR<50)3) other relative contraindications to beta blockade.(PR > 0.24 s, 2nd or 3rd degree AV block,active asthma or reactive airway disease).
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- Modest 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 dysfunctionSummary :definitive evidence for a benefit of CCBs in UA/NSTEMI ispredominantly limited to symptom control.DAVIT STUDY ( Eur Heart J 1984; 5: )Diltiazem Reinfarction Study ( N Engl J Med 1986; 315: 423-9)
40 ACEI & ARBsACE 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 ACEIsARBs: if intolerance to ACEI
42 Antiplatelet therapy class 1 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.Meta-analysis pooled data from 195 trialsInvolving more than 143,000 patients22% reduction in the odds of vascular death, MI, or stroke with antiplatelet therapyAn analysis from the CURE trial suggested that there was no difference in the rate of thrombotic events according to ASA dose, but there was a dose-dependent increase in bleeding in patients receiving ASA (plus placebo): the major bleedingrate was 2.0% in patients taking less than 100 mg of ASA,2.3% with 100 to 200 mg, and 4.0% with greater than 200mg per d (243,376). Therefore, maintenance doses of 75 to162 mg of ASA are preferred.
43 ISIS-2) trial led to the recommendation that ASA be initiated immediately in the ED once the diagnosis of ACS is made or suspected.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 CURE trial :12,562 patients with UA/NSTEMI presenting with in 24 hrsClopidogrel 300mg loading >>>75mg/d v/s placeboAll patients received ASASignificant reductions in the rate of in-hospital severe ischemia and revascularization and need for IV GPIIb/IIIa inhibitors.Strong evidence for addition of clopidogrel to ASA on admission in management of patients in whom a non-interventional approach is intended.Useful approach in hospitals that do not have a routine policy about early invasive proceduresBenefit 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 PRAUGREL-rapidly acting , more potent thienopyridine. -associated with less respose variability than clopidogrelDosage :Prasugrel 60 mg should be given promptly and notlater than 1 hour after PCI once coronary arteryanatomy is defined.Duration and maintenance dose :Prasugrel 10 mg dailyDuration : Up to 12 monthsContraindications :Elderly ≥ 75 years,Body weight <60 kgPrior history of TIA or stroke
47 Prasugrel TRITON TIMII 38 Trial 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.
48 GPIIb/IIIa InhibitorUpstream strategy:Eptifibatide or tirofiban is administered in the ED orhospital for medical stabilization usually in ananticipation for an early invasive approach.Adjunctive strategy:Use either Eptifibatide or Abciximab as adjunctivetherapy immediately before PCI
49 EARLY ACS trial( in 9492 pts with UA/NATEMI)Upstream glycoprotein (GP) IIb/IIIa inhibitorV/SAdjunctive strategy GP IIb/IIIa inhibitorThe 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.
50 Anti coagulant therapy recommendations Class IConservative 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 hrsClass IIaInvasive 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 remainundefined.)
52 UFH v/s EnoxaparinSystematic 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)
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. ACUITY TRIAL UFH+ GPIIb/IIaBivalirudin aloneIschemiaend point byNo clopidogrel loading before PCI at 30dMajor bleeding at 30 daysComposite ischemia end point at 30dIschemiaend point by clopidogrel loading before PCI at 30dAcute 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 CAGPCI, CABG, Medical Mx2. Conservative approach:Medical MxRecurrent Ischemia (at rest /on noninvasive stress test)Revasularization
56 High risk clinical events Recurrent angina/ischemia at restwith low-level activities despiteintensive medical therapyElevated cardiac TnT or TnINew/presumably new ST-segment depressionSigns/symptoms of heart failure or new/worsening mitral regurgitationHigh-risk findings from noninvasive testingHemodynamic instabilitySustained ventricular tachycardiaPCI within 6 monthsPrior CABGHigh 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 Long term Antiplatelet therapy Class IMedical therapyBMS groupDES groupASA mg/d indefinitely&Clopidogrel 75 mg/d for at least 1 month and ideally up to 1 yearASA 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/dOrprasugrel 10mg for at least 1 year
59 Lipid ManagementLipid management should include assessment of a fasting lipidprofile for all patients, within 24 h of hospitalization.High dose statins in the absence of contraindications, regardlessof baseline LDL-C and diet modification, should be given topost-UA/NSTEMI patients, including post revascularizationpatients.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.)