1. Acute Coronary Syndrome
Alena Goldman, MD
September 16, 2004

2. Things to Know…. What is ACS? Quick recognition of ACS?
Classification (think simple… ACS/NSTEMI vs. STEMI)
Sick or not sick (i.e. cath lab/thrombolytics fast?)
Management

3. What is ACS?
ACS = Unstable angina / NSTEMI/ STEMI

4. Pathophysiology Stable USA NSTEMI STEMI Angina
Fixed Plaque Plaque Occluding
Plaque Rupture Rupture Thrombus
Evidence of Myocardial
Myocardial Damage
Damage

5. Recognition of ACS History:
Rest angina, which is usually more than 20 minutes in duration   New onset angina that markedly limits physical activity   Increasing angina that is more frequent, longer in duration, or occurs with less exertion than previous angina

6. Recognition of ACS ECG:
USA/NSTEMI are also called the non-STelevation acute coronary syndromes, i.e. ST elevation and pathologic Q waves are absent
Can see: ST depressions or transient elevations or new T wave inversions
STEMI: ST elevations/reciprocal changes

7. Recognition of ACS Markers of Myocardial Injury:
USA: with ischemic symptoms suggestive of an ACS and no elevation in troponins or CK-MB, with or without ECG changes
NSTEMI: same manifestations as those in USA, but in whom an elevation in troponins or CK-MB is present
STEMI: ischemic symptoms; ST elevations or pathologic Q waves; elevated troponins or CK-MB

8. Importance of Early Recognition!!!
Early interventions, regardless of strategy used, save lives!!!
In addition to reduction in mortality:
Reduce infarct size (reperfusion)
Preserve LV function/prevention of LV remodeling (ACE-I)
Prevent recurrent ischemia and arrhythmias (beta blockers)
Slow disease progression (statins)
Cholesterol lowering (statins)

9. Recognition Triage (sick vs. not sick)
Hemodynamically unstable:
signs of cardiogenic shock (with massive STEMI: large anterior wall MI or inferior MI with RV involvement)
Malignant ventricular arrhythmias
Triage to: cath lab/balloon pump/pressors/CCU

10. Recognition Triage (sick vs. not sick)
2. STEMI:
anginal sxs plus ST elevations 1 mm of greater in two contiguous leads or new LBBB
Triage cath lab vs. lytics if primary PCI not available

11. Recognition Triage (sick vs. not sick)
3. Refractory chest pain:
If good story, elevated markers, suggestive ECG changes:
Triage cath lab

12. Management Sick  cath vs lytics if STEMI STEMI  cath vs. lytics
USA/NSTEMI medical management plus reperfusion (PCI)

13. USA/NSTEMI: Goals of Therapy
Relief of ischemic pain
Assessment of hemodynamic state and correction of abnormalities
Antithrombotic therapy:
-prevent further thrombosis and progression to STEMI
-prevent embolization of plaque

14. USA/NSTEMI: Therapy
Should NOT receive thrombolytics (as opposed to STEMI)
Lack of benefit due to the fact that the infarct-related artery is at least partially patent at early angiography in 60 to 85 percent of cases

15. USA/NSTEMI: Therapy Early PCI vs. Medical Management?
data from TACTICS-TIMI 18:
Primary PCI better especially if + troponin, ST changes, recurrent angina, TIMI score >3, sustained VT, HD instability, h/o prior PCI or CABG

16. USA/NSTEMI: TIMI score
TIMI 11B and ESSENCE trials:
Age 65 years    Presence of at least three risk factors for CHD    Prior coronary stenosis of 50 percent    Presence of ST segment deviation on admission ECG    At least two anginal episodes in prior 24 hours    Elevated serum cardiac biomarkers    Use of aspirin in prior seven days

17. USA/NSTEMI: Initial Therapy
Aspirin
Heparin gtt
Beta blocker
Nitro gtt (careful if suspect inferior/RV involvement and if h/o AS)
….In addition to MONA (Morphine, Oxygen, SL NTG, ASA 81 mg); IV; cardiac monitor

18. ACS/NSTEMI: ASA -Antiplatelet function
-Administration reduces incidence of death and subsequent MI
-Dose: 160 mg to 325 mg immediately followed by 75 mg to 325 mg indefinitely
-Contraindications: allergy; hemophilia; active bleeding; active retinal hemorrhage; active PUD
-If allergic to ASA Plavix

19. USA/NSTENI: Plavix or Ticlid
As effective as ASA
Plavix preferred over Ticlid as it inhibits platelets more rapidly and has less side effects
CURE trial: combo of Plavix plus ASA compared to ASA alone showed decreased cardiovascular death, MI and stroke
In patients undergoing PCI: administration of Plavix 6 hours prior to PCI improves outcome (fewer acute thrombotic complications)
Problem: if patient needs CABG, increased bleeding and reoperation risk

20. USA/NSTEMI: IIb/IIIa inhibitors
Benefits in high risk patients (TIMI score ≥4) or if planned PCI
Tirofiban, eptifibatide, abciximab
Infused for 48 to 72 hours, or until PCI
Small but significant increase in major bleeding (no increase in ICH)

21. USA/NSTEMI: Anticoagulation
Heparin:
-interferes with thrombus formation by different mechanism than ASA
-associated with rebound chest pain if discontinued
-unclear if has efficacy after 24 to 48 hours
-studies show trends towards mortality benefit (Meta Analysis, JAMA 1996)

22. USA/NSTEMI: Anticoagulation
LMWH
-meta-analysis of ESSENCE and TIMI 11B:
enoxaparin vs. unfractionated heparin, an improvement in outcome with enoxaparin, with a 20 percent reduction in death and ischemic events
-Benefits of LMWH: easy administration; no need to follow PTT; mortality benefit; can be used before planned PCI
-Problems with LMWH: should not be used in renal failure (Creatinine clearance less than 30); should not use if planned CABG in 24 hours

23. USA/NSTEMI: Anticoagulation
Direct Thrombin Inhibitors
hirudin, lepirudin, bivalirudin
Decreased incidence of MI compared to heparin but no mortality benefit
Very expensive
Can be used if h/o HIT

24. USA/NSTEMI: beta blockers
Decrease death by 20-30%
Do not use in symptomatic bradycardia; high degree AV block; decompensated CHF; hypotension

25. USA/NSTEMI: Further Medical Management
ACE Inhibitors
-More studies done in patients after STEMI, but likely benefit in all patients after myocardial infarction
-Class I recommendations in patients with left ventricular dysfunction or heart failure, diabetes, and/or hypertension despite therapy with a beta blocker
-Begin therapy in first 24 hours in the absence of contraindication
-HOPE trial (patient without MI): benefit of chronic therapy with ACE-I

26. USA/NSTEMI: Further Medical Management
ARBs
-limited data
-probably should not use combination of ACE-I and ARB (VALIANT trial)

27. USA/NSTEMI: Further Medical Management
Statin Therapy
PROVE IT-TIMI 22 trial suggests that benefit from statin therapy is seen with serum LDL-cholesterol values below 100 mg/dL and that the goal LDL-cholesterol concentration should be less than 80 mg/dL
should be initiated prior to discharge from the hospital in patients with an ACS (between 24 and 96 hours after hospital admission)
trend toward benefit as early as 30 days

28. USA/NSTEMI: Further Medical Management
Aldosterone Antagonists
-EPHESUS trial: Eplerenone was given to patients post MI; LVEF<40; renal failure or diabetes
-significantly lower rate of all-cause mortality
-serum potassium should be monitored closely

29. USA/NSTEMI: Should NOT GET…
Prophylactic antiarrhythmics
Digoxin
CCB

30. STEMI: Quick Recognition!!!
Story
ECG
Serum cardiac enzyme elevation

31. STEMI: Reperfusion Therapy
thrombolytic agents or primary (direct) PCI:
Decision has to be made FAST since prompt restoration of myocardial blood flow is essential to myocardial salvage

32. STEMI: Primary PCI High quality PCI should be immediately available
Enhanced survival with lower are of ICH and recurrent MI
Rapid transfer to a PCI center can still produce better outcomes than thrombolysis, as long as the door-to-balloon time is less than two hours

33. STEMI: Primary PCI, Cont’d
Restores normal epicardial flow in more than 90 percent of cases compared to only 50 to 60 percent with thrombolysis
Mechanical revascularization (usually by PCI) is also the preferred therapy in patients who have contraindications to thrombolysis
In the United States, the median time to PCI after arrival at the hospital is 116 minutes, and exceeds two hours in 46 percent
The longer the door-to-balloon time, the greater the infarct size
TIMI 3 flow is achieved in over 90 percent of patients treated with primary PCI

34. STEMI: Thrombolysis
If PCI not available in 2 hours, patient should be rapidly evaluated for thrombolytic therapy
R/O Contraindications:
evidence of active bleeding, history of cerebrovascular disease, intracranial neoplasm, systolic blood pressure greater than 175 mmHg, trauma, or drug allergy
If no contraindications exist, intravenous thrombolysis should be given within 30 minutes from emergency department presentation

35. STEMI: Thrombolysis
Should be administered within the first four hours and particularly within the first 70 minutes of symptom onset
Most patients present >2 hours after onset of symptoms
Utility of prehospital lytics if transport time >60 min

36. STEMI: Choosing Lytics (from S. Parpos, MD)

37. STEMI: Lytics
Morbidity and mortality benefit is primarily seen in the 50 to 60 percent of patients who develop TIMI grade 3 flow
Possible alternative: combination therapy using a half-dose of a thrombolytic agent combined with a GP IIb/IIIa inhibitor:
-more likely to restore coronary perfusion
-two large trials failed to show a survival benefit compared to conventional thrombolytic therapy

38. STEMI: Delayed Reperfusion
Optimal reperfusion strategy is less clear when the door-to-balloon time will be more than two to three hours
Thrombolytic therapy administered more than 12 hours after the onset of acute myocardial infarction does not improve clinical outcome
Early PCI is also optimal but, in contrast to thrombolysis, revascularization after 12 hours with PCI may be of some benefit

39. STEMI: Antiplatelet Agents
ASA
Plavix or Ticlid: extrapolated data from NSTEMI; most get plavix load in cath lab prior to stent placement
-Limited data on addition of plavix to asa in patients treated with lytis
-Continue plavix for 9-12 months
IIB/IIIA inhibitors:
-used in primary PCI
-so far not recommended in patients receiving lytics

40. STEMI: Medical Therapy
Nitro ggt
Beta Blockers
K and Mg repletion:
HypoK in AMI: risk for VF
Glucose control

41. STEMI: Anticoagulation
Heparin or LMWH
With PCI
With Lytics (if getting asa and alteplase)
Without reperfusion
24-48 hours
Coumadin
-Evidence for use one to three months post-MI in patients at high risk for embolization, especially those with an anterior wall MI (LV thrombus/aneurism; LVEF<30%; h/o thromboembolic disease; h/o afib)

42. STEMI: Further Medical Management
Repeat reperfusion therapy
ACE Inhibitors
ARB
Statin therapy
Aldosterone Antagonists
Risk stratification

43. ACS: Take Home Points Quick recognition HD stable? USA/NSTEMI vs STEMI
STEMI reperfusion (door to balloon time <90 min; door to lytics <30 min)
USA/NSTEMI: no benefit in lytics
All get: MONA; ASA; nitro; beta blockers; heparin or LMWH
High risk patients get IIb/IIIa inhibitors

44. ACS: Take Home Points
USA/NSTEMI patient should get Plavix unless expect CABG
Primary PCI is superior to conservative management in USA/NSTEMI patients
Adjunctive therapy: ACE-I, ARB, statins
Coumadin in patients with LV aneurism/thrombus, LV dysfunction
Post MI patients need risk stratification for primary prevention of sudden cardiac death