acute coronary syndrome dr. s.a. moezzi acs overview overview of acs overview of acs assessment of...
TRANSCRIPT
Acute Coronary Acute Coronary SyndromeSyndrome
Dr. S.A. moezziDr. S.A. moezzi
ACS OverviewACS Overview
Overview of ACSOverview of ACS Assessment of “Likelihood of ACS”Assessment of “Likelihood of ACS” Early Risk StratificationEarly Risk Stratification Invasive vs Conservative StrategyInvasive vs Conservative Strategy PharmacotherapyPharmacotherapy Long-term Therapy/Secondary PreventionLong-term Therapy/Secondary Prevention
Scope of the ProblemScope of the Problem
5 million ER visits nationwide for CP5 million ER visits nationwide for CP 800,000 experience an MI each year800,000 experience an MI each year
213,000 die from their event213,000 die from their event ½ of those die before reaching the ER½ of those die before reaching the ER
Pre-CCU, mortality for MI was >30%Pre-CCU, mortality for MI was >30% Fell to 15% with CCUFell to 15% with CCU
With current interventions, in hospital mortality of With current interventions, in hospital mortality of STEMI is 6-7%STEMI is 6-7%
Overview of ACS
Acute Coronary Syndromes*
1.57 Million Hospital Admissions - ACS
UA/NSTEMI† STEMI
1.24 million Admissions per year
0.33 million Admissions per year
*Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA.Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171.
Acute Coronary Syndrome (ACS)Acute Coronary Syndrome (ACS)
Definition:Definition: The spectrum of acute ischemia The spectrum of acute ischemia related syndromes ranging from UA to MI related syndromes ranging from UA to MI with or without ST elevation with or without ST elevation that are that are secondary to acute plaque rupture or plaque secondary to acute plaque rupture or plaque erosion.erosion.
[----[----UAUA------------------NSTEMINSTEMI--------------------STEMISTEMI----]----]
Decreased O2 Supply
•Flow- limiting stenosis
•Anemia
•Plaque rupture/clot
Increased O2 Demand
O2 supply/demand mismatch→Ischemia
Myocardial ischemia→necrosis
Pathophysiology ACS
Asy
mpt
omat
ic
Ang
ina
Myo
card
ial I
nfar
ctio
n
Pathophysiology of Stable Angina and ACSPathophysiology of Stable Angina and ACS
Pathophysiology of ACSPathophysiology of ACSEvolution of Coronary ThrombosisEvolution of Coronary Thrombosis
Unstable Unstable AnginaAngina STEMISTEMI NSTEMINSTEMI
Non occlusive thrombus
Non specific ECG
Normal cardiac enzymes
Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis
ST depression +/- T wave inversion on ECG
Elevated cardiac enzymes
Complete thrombus occlusion
ST elevations on ECG or new LBBB
Elevated cardiac enzymes
More severe symptoms
STEMISTEMI
Name 3 situations in which you cannot Name 3 situations in which you cannot diagnose STEMIdiagnose STEMI
STEMISTEMI
Name 3 situations in which you cannot Name 3 situations in which you cannot diagnose STEMIdiagnose STEMI
Left Ventricular HypertrophyLeft Ventricular Hypertrophy Chronic or Rate Dependent LBBBChronic or Rate Dependent LBBB Paced RhythmPaced Rhythm
Diagnosis of ACSDiagnosis of ACS
At least 2 of the At least 2 of the followingfollowing History ( angina or angina History ( angina or angina
equivalent)equivalent) Acute ischemic ECG changesAcute ischemic ECG changes Typical rise and fall of cardiac Typical rise and fall of cardiac
markersmarkers Absence of another identifiable Absence of another identifiable
etiologyetiology
Likelihood of ACS by Hx/PELikelihood of ACS by Hx/PE
History/ExaminationHistory/Examination Pain in Chest or Left ArmPain in Chest or Left Arm CP RadiationCP Radiation
Right ShoulderRight Shoulder Left ArmLeft Arm Both Left & Right ArmBoth Left & Right Arm
DiaphoresisDiaphoresis 33rdrd Heart Sound Heart Sound SBP < 80 mm HgSBP < 80 mm Hg Pulmonary Crackles Pulmonary Crackles
Panju AA. Panju AA. JAMA.JAMA. 1998;280:1256. 1998;280:1256.
Suggesting AMISuggesting AMILR 2.7LR 2.7
LR 2.9 (1.4-6.0)LR 2.9 (1.4-6.0)
LR 2.3 (1.7-3.1)LR 2.3 (1.7-3.1)
LR 7.1 (3.6-14.2)LR 7.1 (3.6-14.2)
LR 2.0 (1.9-2.2)LR 2.0 (1.9-2.2)
LR 3.2 (1.6-6.5)LR 3.2 (1.6-6.5)
LR 3.1 (1.8-5.2)LR 3.1 (1.8-5.2)
LR 2.1 (1.4-3.1)LR 2.1 (1.4-3.1)
Likelihood of ACS by Hx/PELikelihood of ACS by Hx/PE
Clinical Examination – Clinical Examination – Pleuritic Chest PainPleuritic Chest Pain Sharp or Stabbing PainSharp or Stabbing Pain Positional Chest PainPositional Chest Pain Reproducible Chest PainReproducible Chest Pain
Panju AA. Panju AA. JAMA.JAMA. 1998;280:1256. 1998;280:1256.
Against AMIAgainst AMI
LR 0.2 (0.2-0.3)LR 0.2 (0.2-0.3)
LR 0.3 (0.2-0.5)LR 0.3 (0.2-0.5)
LR 0.3 (0.2-0.4)LR 0.3 (0.2-0.4)
LR 0.2-0.4LR 0.2-0.4
Risk Stratification by ECGRisk Stratification by ECG
Simple, quick, noninvasive toolSimple, quick, noninvasive tool Universally available, cheapUniversally available, cheap Correlates with risk and prognosisCorrelates with risk and prognosis Guides treatment decisionsGuides treatment decisions Can identify alternative causes Can identify alternative causes
Risk Stratification by ECGRisk Stratification by ECG
ECG Findings and Associated LR for AMIECG Findings and Associated LR for AMI New ST-E New ST-E >> 1mm 1mm LR 5.7-53.9LR 5.7-53.9 New Q wavesNew Q waves LR 5.3-24.8LR 5.3-24.8 Any ST-EAny ST-E LR 11.2 (7.1-17.8)LR 11.2 (7.1-17.8) New Conduction DefectNew Conduction Defect LR 6.3 ( 2.5-15.7)LR 6.3 ( 2.5-15.7) New ST-DNew ST-D LR 3.0-5.2LR 3.0-5.2
NORMAL ECGNORMAL ECG LR 0.1-0.4LR 0.1-0.4
Panju AA. Panju AA. JAMA.JAMA. 1998;280:1256. 1998;280:1256.
Risk Stratification by ECGRisk Stratification by ECG
1-8% AMI have a normal ECG1-8% AMI have a normal ECG
Only Approx 50%Only Approx 50% of AMI patients have of AMI patients have diagnostic changes on theirdiagnostic changes on their initial initial ECG ECG
Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40.Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40.
Risk Stratification by ECGRisk Stratification by ECG
1 ECG cannot exclude AMI1 ECG cannot exclude AMI
Brief sample of a dynamic processBrief sample of a dynamic process
Small regions of ischemia or infarction may be Small regions of ischemia or infarction may be missedmissed
Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40.Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40.
How Sensitive is the ECG Alone?How Sensitive is the ECG Alone?
How Predictive is NTG response?How Predictive is NTG response?
Timing of Release of Various Biomarkers After Timing of Release of Various Biomarkers After Acute Myocardial InfarctionAcute Myocardial Infarction
Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5.
1.01.7
3.4 3.7
6.0
7.5
0
1
2
3
4
5
6
7
8
0 to <0.4 0.4 to <1.0 1.0 to <2.0 2.0 to <5.0 5.0 to <9.0 9.0
Cardiac troponin I (ng/ml)
Mo
rtal
ity
at 4
2 D
ays
831 174 148 134 50 67
%%
%%
%
%
Risk Stratification by TroponinRisk Stratification by Troponin
National Academy of Clinical Biochemistry Laboratory Medicine National Academy of Clinical Biochemistry Laboratory Medicine ((NACBNACB) and the Joint ) and the Joint ESC/ACCF/AHA/WHF ESC/ACCF/AHA/WHF Task Force for the Task Force for the
Redefinition of Myocardial Infarction Redefinition of Myocardial Infarction
• • Cardiac troponin is the Cardiac troponin is the preferred preferred marker for the diagnosis marker for the diagnosis of MI and for risk stratification. CK-MB by mass assay is an of MI and for risk stratification. CK-MB by mass assay is an
acceptable acceptable alternativealternative when troponin in not available. when troponin in not available. • • CK-MB was preferred by the NACB for the detection of CK-MB was preferred by the NACB for the detection of
reinfarctionreinfarction early after the index eventearly after the index event increased increased sensitivity and specificity of cTn sensitivity and specificity of cTn should make it the should make it the
marker of choice it is unnecessary to obtain both values.marker of choice it is unnecessary to obtain both values. Cardiac troponins I and T are Cardiac troponins I and T are equally equally usefuluseful..
Non ACS causes of Troponin ElevationNon ACS causes of Troponin Elevation1.1. Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac
surgery, after-interventionalsurgery, after-interventional closure of ASDs)closure of ASDs)2.2. Congestive heart failure (acute and chronic)Congestive heart failure (acute and chronic)3.3. Aortic valve disease and HOCM with significant LVHAortic valve disease and HOCM with significant LVH4.4. HypertensionHypertension5.5. Hypotension, often with arrhythmiasHypotension, often with arrhythmias6.6. Noncardiac surgery Noncardiac surgery 7.7. Renal failureRenal failure8.8. Critically ill patients, especially with diabetes, respiratory failureCritically ill patients, especially with diabetes, respiratory failure9.9. Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms)Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms)10.10. HypothyroidismHypothyroidism11.11. Coronary vasospasm, including apical ballooning syndromeCoronary vasospasm, including apical ballooning syndrome12.12. Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, 13.13. Post-PCI Post-PCI 14.14. Pulmonary embolism, severe pulmonary hypertensionPulmonary embolism, severe pulmonary hypertension15.15. SepsisSepsis16.16. Burns, especially if TBSA greater than 30%Burns, especially if TBSA greater than 30%17.17. Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and sclerodermaInfiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma18.18. Acute neurologic disease, including CVA, subarchnoid bleedsAcute neurologic disease, including CVA, subarchnoid bleeds19.19. Rhabdomyolysis with cardiac injuryRhabdomyolysis with cardiac injury20.20. Transplant vasculopathyTransplant vasculopathy21.21. Vital exhaustionVital exhaustion
Modified from Apple FS, et al Heart J. 2002;144:981-986.
Combined Sensitivities for ACSCombined Sensitivities for ACS
Unstable angina/NSTEMI cardiac Unstable angina/NSTEMI cardiac carecare
Evaluate for Evaluate for conservative vs. invasiveconservative vs. invasive strategy strategy based upon:based upon:
Likelihood of actual ACSLikelihood of actual ACS Risk stratification by Risk stratification by TIMI risk scoreTIMI risk score ACS risk categories per AHA guidelinesACS risk categories per AHA guidelines
LowLowIntermediateIntermediate
HighHigh
TIMI Risk Score
Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days
TIMI Risk ScoreTIMI Risk Score
T: Troponin elevation (or CK-MB elevation)H: History or CAD (>50% Stenosis)R: Risk Factors: > 3 (HTN, Hyperlipidemia, Family Hx, DM II, Active Smoker) E: EKG changes: ST elevation or depression 0.5 mm concordant leadsA2:Aspirin use within the past 7 days; Age over 65T: Two or more episodes of CP within 24 hours
Deciding between Early Invasive vs a Conservative StrategiesDeciding between Early Invasive vs a Conservative Strategies
Definitive/Possible ACSDefinitive/Possible ACSInitiate ASA, BB, Nitrates, Initiate ASA, BB, Nitrates, Anticoagulants, TelemetryAnticoagulants, Telemetry
Early Invasive StrategyEarly Invasive Strategy
• TIMI Risk Score TIMI Risk Score >>33• New ST segment New ST segment deviationdeviation• Positive biomarkersPositive biomarkers
Conservative StrategyConservative Strategy
•TIMI Risk Score <3 (Esp. Women)TIMI Risk Score <3 (Esp. Women)•No ST segment deviationNo ST segment deviation•Negative BiomarkersNegative Biomarkers
Coronary angiographyCoronary angiography(24-48 hours)(24-48 hours)
Recurrent Signs/SymptomsRecurrent Signs/SymptomsHeart failureHeart failureArrhythmiasArrhythmias
Remains StableRemains Stable↓↓
Assess EF and/or Stress TestingAssess EF and/or Stress Testing↓↓
EF<40% OR Positive stressEF<40% OR Positive stressGo to AngiographyGo to Angiography
•Hemodynamic instabilityHemodynamic instability•Elecrical instabilityElecrical instability•Refractory anginaRefractory angina•PCI in past 6 monthsPCI in past 6 months•CABGCABG•EF <40%EF <40%
Specifics of Early Hospital CareSpecifics of Early Hospital Care
Anti-Ischemic TherapyAnti-Ischemic TherapyAnti-Platelet TherapyAnti-Platelet TherapyAnticoagulant TherapyAnticoagulant Therapy
Early Hospital CareEarly Hospital CareAnti-Ischemic TherapyAnti-Ischemic Therapy
Class IClass I Bed/Chair rest and TelemetryBed/Chair rest and Telemetry OxygenOxygen (maintain saturation >90%) (maintain saturation >90%) NitratesNitrates (SLx3 Oral/topical. IV for ongoing iscemia, heart (SLx3 Oral/topical. IV for ongoing iscemia, heart
failure, hypertension)failure, hypertension) Oral Oral BB-blockers-blockers in First 24-hours if no contraindications. in First 24-hours if no contraindications.
(IV (IV BB-blockers class IIa indication)-blockers class IIa indication) Non-dihydropyridine Non-dihydropyridine Ca-channel blockersCa-channel blockers for those with for those with
contraindication fo B-blockerscontraindication fo B-blockers ACE inhibitorsACE inhibitors in first 24-hours for heart failure or in first 24-hours for heart failure or
EF<40% (Class IIa for all other pts) (EF<40% (Class IIa for all other pts) (ARBsARBs for those for those intolerant)intolerant)
StatinsStatins
Early Hospital CareEarly Hospital CareAnti-Ischemic TherapyAnti-Ischemic Therapy
Class IIIClass III Nitrates if Nitrates if BP<90 mmHg or RV infarctionBP<90 mmHg or RV infarction Nitrates within 24-hrs of Nitrates within 24-hrs of SildenafilSildenafil or 48 hrs of or 48 hrs of TadalafilTadalafil Immediate release dihydropyradine Ca-blockersImmediate release dihydropyradine Ca-blockers in the in the
absence of B-Blocker therapyabsence of B-Blocker therapy IV ACE-inhibitorsIV ACE-inhibitors IV IV BB-blockers-blockers in patients with acute HF, Low output state in patients with acute HF, Low output state
or cardiogenic shock, PR interval >0.24 sec, 2or cardiogenic shock, PR interval >0.24 sec, 2ndnd or 3 or 3rdrd degree heart block, active asthma, or reactive airway degree heart block, active asthma, or reactive airway diseasedisease
NSAIDS and Cox-2 inhibitorsNSAIDS and Cox-2 inhibitors
Early Hospital CareEarly Hospital CareAnti-Platelet TherapyAnti-Platelet Therapy
Class IClass I AspirinAspirin (162-325 mg), non enteric coated (162-325 mg), non enteric coated ClopidogrelClopidogrel for those with Aspirin for those with Aspirin
allergy/intolerance (300-600 mg load and 75 mg/d)allergy/intolerance (300-600 mg load and 75 mg/d) GI prophylaxis if a Hx of GI bleedGI prophylaxis if a Hx of GI bleed GP IIb/IIIa inhibitorsGP IIb/IIIa inhibitors should be evaluated based on should be evaluated based on
whether an invasive or conservative strategy is usedwhether an invasive or conservative strategy is used GP IIb/IIIa inhibitors recommended for all GP IIb/IIIa inhibitors recommended for all diabeticsdiabetics
and all patient in early invasive armand all patient in early invasive arm
secondary preventionsecondary prevention
At present, the United States Food and Drug At present, the United States Food and Drug Administration recommends daily doses Administration recommends daily doses of 75 of 75 to 325 mgto 325 mg, ,
the 2006 American College of Cardiology the 2006 American College of Cardiology /American Heart Association (ACC/AHA) /American Heart Association (ACC/AHA) guidelines on recommends daily doses of guidelines on recommends daily doses of 75 to 75 to 162 mg 162 mg for secondary prevention [38]. for secondary prevention [38].
The ACCP recommends a daily dose of The ACCP recommends a daily dose of 75 to 75 to 100 mg100 mg
Early Hospital CareEarly Hospital CareAnticoagulant TherapyAnticoagulant Therapy
Class IClass I Unfractionated HeparinUnfractionated Heparin EnoxaparinEnoxaparin BivalarudinBivalarudin FondaparinuxFondaparinux
Relative choice depends on invasive vs Relative choice depends on invasive vs conservative strategy and bleeding riskconservative strategy and bleeding risk
Early Hospital CareEarly Hospital CareStatin TherapyStatin Therapy
MIRACL TrialMIRACL TrialInclusion CriteriaInclusion Criteria 3086 patients with Non ST ACS3086 patients with Non ST ACS Total cholesterol <270 mg/dlTotal cholesterol <270 mg/dl No planned PCINo planned PCI Randomized to Randomized to Atorvastatin vs PlaceboAtorvastatin vs Placebo Drug started at 24-96 hoursDrug started at 24-96 hours
Statin Evidence: MIRACL StudyStatin Evidence: MIRACL Study
Relative risk = 0.84P = .04895% CI 0.701-0.999
Atorvastatin
Placebo
0
5
10
15
0 4 8 12 16
Time Since Randomization (weeks)
Cu
mu
lati
ve In
cid
ence
(%
)
Time to first occurrence of:• Death (any cause)• Nonfatal MI• Resuscitated cardiac arrest• Worsening angina with new
objective evidence and urgent rehospitalization
17.4%
14.8%
Primary Efficacy Measure
Schwartz GG, et al. JAMA. 2001;285:1711-1718.
Statin Evidence: MIRACL StudyStatin Evidence: MIRACL Study
0
0.5
1
1.5
2
0 4 8 12 16
Time Since Randomization (weeks)
Cu
mu
lati
ve In
cid
ence
(%
)
Relative risk = 0.49P = .0495% CI 0.24-0.98
Atorvastatin
Placebo
Fatal and Nonfatal Stroke
Waters DD, et al. Circulation. 2002;106:1690-1695. S24
All-Cause Death or Major CV Events in All Randomized Subjects
00 33 1818 2121 2424 2727 303066 99 1212 1515
% with
Event
Months of Follow-up
Pravastatin 40mgPravastatin 40mg(26.3%)(26.3%)
Atorvastatin 80mgAtorvastatin 80mg(22.4%)(22.4%)
16% RR16% RR
(P = (P = 0.005)0.005)
3030
2525
2020
1515
1010
55
00
PROVE-IT TrialPROVE-IT Trial
Summary of PROVE-IT Results Summary of PROVE-IT Results
In patients recently hospitalized within 10 days for an In patients recently hospitalized within 10 days for an acute coronary syndrome: acute coronary syndrome:
““Intensive” high-dose LDL-C loweringIntensive” high-dose LDL-C lowering (median LDL-C 62 (median LDL-C 62 mg/dL) compared to “moderate” standard-dose lipid-lowering mg/dL) compared to “moderate” standard-dose lipid-lowering therapy (median LDL-C 95 mg/dL) therapy (median LDL-C 95 mg/dL) reduced the risk of all cause reduced the risk of all cause mortality or major cardiac events by 16%mortality or major cardiac events by 16% (p=0.005) (p=0.005)
BenefitsBenefits emerged emerged within 30 dayswithin 30 days post ACS with continued benefit post ACS with continued benefit observed throughout the observed throughout the 2.5 years of follow-up2.5 years of follow-up
Benefits were consistent across all cardiovascular endpoints, Benefits were consistent across all cardiovascular endpoints, except stroke, and most clinical subgroups except stroke, and most clinical subgroups
Invasive vs Conservative Invasive vs Conservative StrategiesStrategies
Invasive vs Conservative Strategy Invasive vs Conservative Strategy Clinical TrialsClinical Trials
TIMI IIIB (94)
ConservativeStrategy Favored
N=920
InvasiveStrategy Favored
N=7,018
VANQWISH (98)
MATE
FRISC II (99)
TACTICS-TIMI 18 (01)
VINO
RITA-3 (02)
TRUCS
ISAR-COOL
ICTUS (05)
No differenceNo differenceN=2,874N=2,874
Weight ofWeight ofthe evidencethe evidence
How Early is Early?How Early is Early?
Secondary PreventionSecondary PreventionClass I IndicationsClass I Indications
AspirinAspirin Beta-blockers:Beta-blockers: (all pts, slow titration with moderate to (all pts, slow titration with moderate to
severe failuresevere failure ACE-Inhibitors: ACE-Inhibitors: CHF, EF<40%, HTN, DMCHF, EF<40%, HTN, DM (All pts-Class IIa) (All pts-Class IIa) ARBARB when intolerant to ACE. when intolerant to ACE.
(Class IIa as alternative to ACEI)(Class IIa as alternative to ACEI)Aldosterone blockade:Aldosterone blockade: An ACEI, CHF with either An ACEI, CHF with either
EF<40% or DM and if CrCl>30 ml/min and KEF<40% or DM and if CrCl>30 ml/min and K<<5.0 5.0 mEq/LmEq/L
StatinsStatins Standard Risk Factor ManagementStandard Risk Factor Management
Long-Term Antithrombotic Therapy at Hospital Discharge after UA/NSTEMI
Medical Therapy without Stent
Bare Metal Stent Group
Drug Eluting Stent Group
ASA 162 to 325 mg/d for at least 1 month, then 75 to 162 mg/d indefinitely
(Class I, LOE: A)
&Clopidogrel 75 mg/d for at least 1 month and up to 1
year (Class I, LOE:B)
Add: Warfarin (INR 2.0 to 2.5) (Class IIb, LOE: B)
Continue with dual antiplatelet therapy as
above
Yes
No
Indication for Anticoagulation?
ASA 75 to 162 mg/d indefinitely (Class I,
LOE: A)
&
Clopidogrel 75 mg/d at least 1 month (Class I, LOE: A) and up to 1 year (Class I, LOE: B)
ASA 162 to 325 mg/d for at least 3 to 6
months, then 75 to 162 mg/d indefinitely (Class I, LOE: A)
&
Clopidogrel 75 mg/d for at least 1 year (Class I, LOE: B)
Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 11. INR = international normalized ratio; LOE = level of evidence.
UA/NSTEMI Patient
Groups at Discharge
New
Secondary PreventionSecondary PreventionClass IIIClass III
Hormone Replacement TherapyHormone Replacement Therapy Antioxidants (Vit C, Vit E)Antioxidants (Vit C, Vit E) Folic AcidFolic Acid
Early Treatment with ClopidogrelEarly Treatment with Clopidogrel
Shortcomings of the CURE TrialShortcomings of the CURE Trial
Conducted primarily at centers Conducted primarily at centers without routine without routine use of early invasive strategyuse of early invasive strategy
Only 462 Only 462 (3.7%)(3.7%) patients enrolled from the patients enrolled from the U.SU.S.. 44% had catheterization during index 44% had catheterization during index
hospitalizationhospitalization Adverse event reduced only in nonfatal MI setAdverse event reduced only in nonfatal MI set Major Bleeding rate of 9.6% among patients Major Bleeding rate of 9.6% among patients
who were administered clopidogrel within 5 who were administered clopidogrel within 5 days of CABGdays of CABG
ClopidogrelClopidogrelBleeding Risk and CABGBleeding Risk and CABG
““In hospitals in which patients with In hospitals in which patients with UA/NSTEMI undergo rapid diagnostic UA/NSTEMI undergo rapid diagnostic catheterization within 24 hours of admission, catheterization within 24 hours of admission, clopidogrel is not started until it is clear that clopidogrel is not started until it is clear that CABG will not be scheduled within the next CABG will not be scheduled within the next several days. However, unstable patients several days. However, unstable patients should receive clopidogrel or be take for should receive clopidogrel or be take for immediate angiography.”immediate angiography.”
Clopidogrel vs. PrasugrelClopidogrel vs. Prasugrel
Prasugrel-Key FactsPrasugrel-Key Facts
ContraindicatedContraindicated in pts with in pts with prior TIA/Strokeprior TIA/Stroke Not recommended for patients Not recommended for patients >>75 years75 years 5 mg maintenance dose suggested in patients 5 mg maintenance dose suggested in patients
<60 Kg<60 Kg, though this dose has not been studied, though this dose has not been studied
SummarySummary
ACS includes UA, NSTEMI, and STEMIACS includes UA, NSTEMI, and STEMI
Management guideline focusManagement guideline focus Immediate assessment/intervention Immediate assessment/intervention (MONA+BAH)(MONA+BAH) Risk stratification Risk stratification (UA/NSTEMI vs. STEMI)(UA/NSTEMI vs. STEMI) RAPID reperfusion for STEMI RAPID reperfusion for STEMI (PCI vs. Thrombolytics)(PCI vs. Thrombolytics) Conservative vs Invasive therapy for UA/NSTEMIConservative vs Invasive therapy for UA/NSTEMI
Aggressive attention to secondary prevention Aggressive attention to secondary prevention initiatives for ACS patients initiatives for ACS patients
Beta blocker, ASA, ACE-I, StatinBeta blocker, ASA, ACE-I, Statin
Ten Points to Remember Ten Points to Remember from thefrom the
2009 STEMI Guideline Update 2009 STEMI Guideline Update
Antman EM, Hand M,Antman EM, Hand M,Armstrong PW, et al., Armstrong PW, et al.,
1.1. Patients routinely taking NSAIDs (except for Patients routinely taking NSAIDs (except for aspirin), both nonselective as well as COX-2 aspirin), both nonselective as well as COX-2 selective agents, before STEMI should have selective agents, before STEMI should have those agents those agents discontinueddiscontinued at the time of at the time of presentation with STEMI because of the presentation with STEMI because of the increased risk of increased risk of mortalitymortality, , reinfarctionreinfarction, , hypertension, heart failure, and myocardial hypertension, heart failure, and myocardial rupturerupture associated with their use. associated with their use.
Ten Points to RememberTen Points to Remember from the from the
2009 STEMI Guideline Update2009 STEMI Guideline Update
2.2. Oral beta-blocker therapy should be initiated in the Oral beta-blocker therapy should be initiated in the first 24 hours for patients who do first 24 hours for patients who do notnot have any of the have any of the following: following:
a)a) Signs of heart failure Signs of heart failure
b)b) Evidence of a low output state Evidence of a low output state
c)c) Increased risk for cardiogenic shock Increased risk for cardiogenic shock d)d) Other relative contraindications to beta blockadeOther relative contraindications to beta blockade
PR interval > 0.24 seconds PR interval > 0.24 seconds Second- or third-degree heart block Second- or third-degree heart block Active asthma or reactive airway disease Active asthma or reactive airway disease
Ten Points to RememberTen Points to Remember from the from the
2009 STEMI Guideline Update2009 STEMI Guideline Update
3.3. STEMI patients presenting to a hospital with PCI STEMI patients presenting to a hospital with PCI capability should be treated with primary PCI within capability should be treated with primary PCI within 90 minutes of first medical contact as a systems goal.90 minutes of first medical contact as a systems goal.
4.4. STEMI patients presenting to a hospital without PCI STEMI patients presenting to a hospital without PCI capability and who cannot be transferred to a PCI capability and who cannot be transferred to a PCI center and undergo PCI within 90 minutes of first center and undergo PCI within 90 minutes of first medical contact should be treated with fibrinolytic medical contact should be treated with fibrinolytic therapy within 30 minutes of hospital presentation as therapy within 30 minutes of hospital presentation as a systems goal unless fibrinolytic therapy is a systems goal unless fibrinolytic therapy is contraindicated.contraindicated.
Ten Points to RememberTen Points to Remember from the from the
2009 STEMI Guideline Update2009 STEMI Guideline Update
Ten Points to RememberTen Points to Remember from the from the
2009 STEMI Guideline Update2009 STEMI Guideline Update
5.5. A strategy of coronary angiography with intent to A strategy of coronary angiography with intent to perform PCI (or emergency CABG) is recommended perform PCI (or emergency CABG) is recommended for patients who have received fibrinolytic therapy for patients who have received fibrinolytic therapy and have any of the following: and have any of the following:
• Cardiogenic shock in patients <75 years who are suitable Cardiogenic shock in patients <75 years who are suitable candidates for revascularization, candidates for revascularization,
• Severe congestive heart failure and/or pulmonary edema Severe congestive heart failure and/or pulmonary edema (Killip class III), or(Killip class III), or
• Hemodynamically compromising ventricular arrhythmias Hemodynamically compromising ventricular arrhythmias
Ten Points to RememberTen Points to Remember from the from the
2009 STEMI Guideline Update2009 STEMI Guideline Update
6.6. Patients undergoing reperfusion with fibrinolytics Patients undergoing reperfusion with fibrinolytics should receive anticoagulant therapy for a should receive anticoagulant therapy for a minimum of 48 hours and preferably for the minimum of 48 hours and preferably for the duration of the index hospitalization, up to 8 days duration of the index hospitalization, up to 8 days (regimens other than unfractionated heparin [UFH] (regimens other than unfractionated heparin [UFH] are recommended if anticoagulant therapy is given are recommended if anticoagulant therapy is given for more than 48 hours because of the risk of for more than 48 hours because of the risk of heparin- induced thrombocytopenia with prolonged heparin- induced thrombocytopenia with prolonged UFH treatment).UFH treatment).
Ten Points to RememberTen Points to Remember from the from the
2009 STEMI Guideline Update2009 STEMI Guideline Update
7.7. Clopidogrel 75 mg per day orally should be added Clopidogrel 75 mg per day orally should be added to aspirin in patients with STEMI regardless of to aspirin in patients with STEMI regardless of whether they undergo reperfusion with whether they undergo reperfusion with fibrinolytic therapy or do not receive reperfusion fibrinolytic therapy or do not receive reperfusion therapy. Treatment with clopidogrel should therapy. Treatment with clopidogrel should continue for at least 14 days.continue for at least 14 days.
8.8. Every tobacco user and family members who Every tobacco user and family members who smoke should be advised to quit at every visit.smoke should be advised to quit at every visit.
Ten Points to RememberTen Points to Remember from the from the
2007 STEMI Guideline Update2007 STEMI Guideline Update
9.9. For all post-PCI STEMI stented patients without For all post-PCI STEMI stented patients without aspirin resistance, allergy, or increased risk of aspirin resistance, allergy, or increased risk of bleeding, aspirin at a dose of 162-325 mg daily bleeding, aspirin at a dose of 162-325 mg daily should be given for at least 1 month after bare-should be given for at least 1 month after bare-metal stent (BMS) implantation, 3 months after metal stent (BMS) implantation, 3 months after sirolimus-eluting stent implantation, and 6 months sirolimus-eluting stent implantation, and 6 months after paclitaxel-eluting stent implantation, after after paclitaxel-eluting stent implantation, after which long-term aspirin use should be continued which long-term aspirin use should be continued indefinitely at a dose of 75-162 mg daily.indefinitely at a dose of 75-162 mg daily.
Ten Points to RememberTen Points to Remember from the from the
2007 STEMI Guideline Update2007 STEMI Guideline Update
10.10. For all post-PCI patients who receive a drug-For all post-PCI patients who receive a drug-eluting stent, clopidogrel 75 mg daily should be eluting stent, clopidogrel 75 mg daily should be given for at least 12 months if patients are not at given for at least 12 months if patients are not at high risk of bleeding. For post-PCI patients high risk of bleeding. For post-PCI patients receiving a BMS, clopidogrel should be given for a receiving a BMS, clopidogrel should be given for a minimum of 1 month and ideally up to 12 months minimum of 1 month and ideally up to 12 months (unless the patient is at increased risk of bleeding; (unless the patient is at increased risk of bleeding; then it should be given for a minimum of 2 weeks). then it should be given for a minimum of 2 weeks).
ACC/AHA Guideline Classification System ACC/AHA Guideline Classification System Level of Evidence (LOE)Level of Evidence (LOE)
LOE A – strong evidence Multiple large randomized trials
LOE B – Intermediate
Limited # or small trials Nonrandomized studies/observational registries
LOE C – Expert consensus/Opinion
Beta-blockers in STEMIBeta-blockers in STEMI Class I - oral beta-blockers should be initiated within 24 Class I - oral beta-blockers should be initiated within 24
hourshours* * LOE BLOE B
Class IIa - reasonable to administer IV beta-blocker at the time Class IIa - reasonable to administer IV beta-blocker at the time of presentation who are hypertensiveof presentation who are hypertensive* * LOE BLOE B
Class III - IV beta-blockers should not be administered to Class III - IV beta-blockers should not be administered to patients with any of the followingpatients with any of the following* * LOE ALOE A
** Contraindications include Contraindications include 1)1) signs of heart failure, signs of heart failure, 2)2) evidence of low output state, evidence of low output state, 3)3) risk for cardiogenic shock (age>70, SBP<120, sinus tach>110bpm, HR<60, risk for cardiogenic shock (age>70, SBP<120, sinus tach>110bpm, HR<60, increased time since onset of STEMI), increased time since onset of STEMI), 4)4) or other relative contraindication or other relative contraindication (PR>0.24s, heart block, active asthma)(PR>0.24s, heart block, active asthma)
UFH/ LMWH in STEMIUFH/ LMWH in STEMI Class I - Patients receiving fibrinolytics should receive Class I - Patients receiving fibrinolytics should receive
anticoagulant therapy for a minimum of 48 hrs, LOE C. anticoagulant therapy for a minimum of 48 hrs, LOE C. Because of heparin induced thrombocytopenia, regimens other Because of heparin induced thrombocytopenia, regimens other than UFH are recommended for patients receiving than UFH are recommended for patients receiving anticoagulant therapy > 48 hrs, LOE A.anticoagulant therapy > 48 hrs, LOE A.
DOSE:DOSE: UFH - 60 U/kg (max 4000 U) bolus, then 12 U/kg per hr dripUFH - 60 U/kg (max 4000 U) bolus, then 12 U/kg per hr drip Enoxaparin - (Cr <2.5 men, <2.0 women)Enoxaparin - (Cr <2.5 men, <2.0 women)
For pts age <75 give 30mg IV bolus followed 15min later by 1 mg/kg For pts age <75 give 30mg IV bolus followed 15min later by 1 mg/kg subq. subq.
For pts >=75, no IV bolus and reduce subq dose to 0.75 mg/kg For pts >=75, no IV bolus and reduce subq dose to 0.75 mg/kg
Clopidogrel in STEMIClopidogrel in STEMI
Class I - Clopidogrel 75mg/ day should be Class I - Clopidogrel 75mg/ day should be added to ASA in pts with STEMI regardless of added to ASA in pts with STEMI regardless of fibrinolytic use LOE Afibrinolytic use LOE A
Class IIa - In patients < 75yo, it is reasonable Class IIa - In patients < 75yo, it is reasonable to consider a loading dose of 300mg LOE C to consider a loading dose of 300mg LOE C
- - recent studies suggest a loading dose of Plavix 600mgrecent studies suggest a loading dose of Plavix 600mg
Questions?Questions?