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Slide 65 -
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Acute Coronary Syndrome Steven R. Bruhl MD, MS
3rd Year Cardiology Fellow
Internal Medicine Didactics
July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS
Recognize the clinical features of low, intermediate and high risk ACS
Be able to identify and treat patients appropriate for a conservative or invasive strategy
Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction
http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS.
Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS
Assessment of “Likelihood of ACS”
Early Risk Stratification
Invasive vs Conservative Strategy
Pharmacotherapy
Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP
800,000 experience an MI each year
213,000 die from their event
½ of those die before reaching the ER
Pre-CCU, mortality for MI was >30%
Fell to 15% with CCU
With current interventions, in hospital mortality of 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)
Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion.
[----UA---------NSTEMI----------STEMI----]
Decreased O2 Supply
Flow- limiting stenosis
Anemia
Plaque rupture/clot
Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI 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 STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI
Left Ventricular Hypertrophy
Chronic or Rate Dependent LBBB
Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization.
Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization.
STEMI or new LBBB
ACS with hemodynamic or electrical instability despite optimal medical management
Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following
History ( angina or angina equivalent)
Acute ischemic ECG changes
Typical rise and fall of cardiac markers
Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination
Pain in Chest or Left Arm
CP Radiation
Right Shoulder
Left Arm
Both Left & Right Arm
Diaphoresis
3rd Heart Sound
SBP < 80 mm Hg
Pulmonary Crackles
Panju AA. JAMA. 1998;280:1256. Suggesting AMI
LR 2.7
LR 2.9 (1.4-6.0)
LR 2.3 (1.7-3.1)
LR 7.1 (3.6-14.2)
LR 2.0 (1.9-2.2)
LR 3.2 (1.6-6.5)
LR 3.1 (1.8-5.2)
LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination –
Pleuritic Chest Pain
Sharp or Stabbing Pain
Positional Chest Pain
Reproducible Chest Pain
Panju AA. JAMA. 1998;280:1256. Against AMI
LR 0.2 (0.2-0.3)
LR 0.3 (0.2-0.5)
LR 0.3 (0.2-0.4)
LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool
Universally available, cheap
Correlates with risk and prognosis
Guides treatment decisions
Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI
New ST-E > 1mm LR 5.7-53.9
New Q waves LR 5.3-24.8
Any ST-E LR 11.2 (7.1-17.8)
New Conduction Defect LR 6.3 ( 2.5-15.7)
New ST-D LR 3.0-5.2
NORMAL ECG LR 0.1-0.4
Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS
1-8% AMI have a normal ECG
Only Approx 50% of AMI patients have diagnostic changes on their initial ECG
Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont.
1 ECG cannot exclude AMI
Brief sample of a dynamic process
Small regions of ischemia or infarction may be missed
Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute 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. Mortality at 42 Days 831 174 148 134 50 67 % %
% % % % Risk Stratification by Troponin Non ACS causes of Troponin Elevation Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs)
Congestive heart failure (acute and chronic)
Aortic valve disease and HOCM with significant LVH
Hypertension
Hypotension, often with arrhythmias
Noncardiac surgery
Renal failure
Critically ill patients, especially with diabetes, respiratory failure
Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms)
Hypothyroidism
Coronary vasospasm, including apical ballooning syndrome
Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination,
Post-PCI
Pulmonary embolism, severe pulmonary hypertension
Sepsis
Burns, especially if TBSA greater than 30%
Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma
Acute neurologic disease, including CVA, subarchnoid bleeds
Rhabdomyolysis with cardiac injury
Transplant vasculopathy
Vital exhaustion Modified from Apple FS, et al Heart J. 2002;144:981-986. Combined Sensitivities for ACS Early Invasive Conservative Unstable angina/NSTEMI cardiac care Evaluate for conservative vs. invasive strategy based upon:
Likelihood of actual ACS
Risk stratification by TIMI risk score
ACS risk categories per AHA guidelines
Low Intermediate High TIMI Risk Score
Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days
TIMI 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 leads
A2:Aspirin use within the past 7 days; Age over 65
T: Two or more episodes of CP within 2 hours Deciding between Early Invasive vs a Conservative Strategies Hemodynamic instability
Elecrical instability
Refractory angina
PCI in past 6 months
CABG
EF <40% Specifics of Early Hospital Care Anti-Ischemic Therapy
Anti-Platelet Therapy
Anticoagulant Therapy Early Hospital Care Anti-Ischemic Therapy Class I
Bed/Chair rest and Telemetry
Oxygen (maintain saturation >90%)
Nitrates (SLx3 Oral/topical. IV for ongoing iscemia, heart failure, hypertension)
Oral B-blockers in First 24-hours if no contraindications. (IV B-blockers class IIa indication)
Non-dihydropyridine Ca-channel blockers for those with contraindication fo B-blockers
ACE inhibitors in first 24-hours for heart failure or EF<40% (Class IIa for all other pts) (ARBs for those intolerant)
Statins Early Hospital Care Anti-Ischemic Therapy Class III
Nitrates if BP<90 mmHg or RV infarction
Nitrates within 24-hrs of Sildenafil or 48 hrs of Tadalafil
Immediate release dihydropyradine Ca-blockers in the absence of B-Blocker therapy
IV ACE-inhibitors
IV B-blockers in patients with acute HF, Low output state or cardiogenic shock, PR interval >0.24 sec, 2nd or 3rd degree heart block, active asthma, or reactive airway disease
NSAIDS and Cox-2 inhibitors Early Hospital Care Anti-Platelet Therapy Class I
Aspirin (162-325 mg), non enteric coated
Clopidogrel for those with Aspirin allergy/intolerance (300-600 mg load and 75 mg/d)
GI prophylaxis if a Hx of GI bleed
GP IIb/IIIa inhibitors should be evaluated based on whether an invasive or conservative strategy is used
GP IIb/IIIa inhibitors recommended for all diabetics and all patient in early invasive arm Early Hospital Care Anticoagulant Therapy Class I
Unfractionated Heparin
Enoxaparin
Bivalarudin
Fondaparinux
Relative choice depends on invasive vs conservative strategy and bleeding risk Early Hospital Care Statin Therapy MIRACL Trial Inclusion Criteria
3086 patients with Non ST ACS
Total cholesterol <270 mg/dl
No planned PCI
Randomized to Atorvastatin vs Placebo
Drug started at 24-96 hours Statin Evidence: MIRACL Study Relative risk = 0.84 P = .048
95% CI 0.701-0.999 Atorvastatin Placebo 0 5 10 15 0 4 8 12 16 Time Since Randomization (weeks) Cumulative Incidence (%) 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 Study 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 0 3 18 21 24 27 30 6 9 12 15 % with Event Months of Follow-up Pravastatin 40mg
(26.3%) Atorvastatin 80mg
(22.4%) 16% RR
(P = 0.005) 30 25 20 15 10 5 0 PROVE-IT Trial Summary of PROVE-IT Results In patients recently hospitalized within 10 days for an acute coronary syndrome:
“Intensive” high-dose LDL-C lowering (median LDL-C 62 mg/dL) compared to “moderate” standard-dose lipid-lowering therapy (median LDL-C 95 mg/dL) reduced the risk of all cause mortality or major cardiac events by 16% (p=0.005)
Benefits emerged within 30 days post ACS with continued benefit observed throughout the 2.5 years of follow-up
Benefits were consistent across all cardiovascular endpoints, except stroke, and most clinical subgroups Invasive vs Conservative Strategies Invasive vs Conservative Strategy Clinical Trials TIMI IIIB (94) Conservative Strategy Favored
N=920 Invasive Strategy Favored
N=7,018 VANQWISH (98) MATE FRISC II (99) TACTICS- TIMI 18 (01) VINO RITA-3 (02) TRUCS ISAR- COOL ICTUS (05) No difference
N=2,874 Weight of
the evidence How Early is Early? Secondary Prevention Class I Indications Aspirin
Beta-blockers: (all pts, slow titration with moderate to severe failure
ACE-Inhibitors: CHF, EF<40%, HTN, DM
(All pts-Class IIa) ARB when intolerant to ACE. (Class IIa as alternative to ACEI)
Aldosterone blockade: An ACEI, CHF with either EF<40% or DM and if CrCl>30 ml/min and K<5.0 mEq/L
Statins
Standard 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 Secondary Prevention Class III Hormone Replacement Therapy
Antioxidants (Vit C, Vit E)
Folic Acid New and Controversial Drug Therapies Early Treatment with Clopidogrel Shortcomings of the CURE Trial Conducted primarily at centers without routine use of early invasive strategy
Only 462 (3.7%) patients enrolled from the U.S.
44% had catheterization during index hospitalization
Adverse event reduced only in nonfatal MI set
Major Bleeding rate of 9.6% among patients who were administered clopidogrel within 5 days of CABG Clopidogrel Bleeding Risk and CABG “In hospitals in which patients with UA/NSTEMI undergo rapid diagnostic catheterization within 24 hours of admission, clopidogrel is not started until it is clear that CABG will not be scheduled within the next several days. However, unstable patients should receive clopidogrel or be take for immediate angiography.” Clopidogrel vs. Prasugrel Prasugrel-Key Facts Contraindicated in pts with prior TIA/Stroke
Not recommended for patients >75 years
5 mg maintenance dose suggested in patients <60 Kg, though this dose has not been studied Summary ACS includes UA, NSTEMI, and STEMI
Management guideline focus
Immediate assessment/intervention (MONA+BAH)
Risk stratification (UA/NSTEMI vs. STEMI)
RAPID reperfusion for STEMI (PCI vs. Thrombolytics)
Conservative vs Invasive therapy for UA/NSTEMI
Aggressive attention to secondary prevention initiatives for ACS patients
Beta blocker, ASA, ACE-I, Statin
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