Acute Coronary Syndrome

Alena Goldman, MD

September 16, 2004

Things to Know….

1. What is ACS?

2. Quick recognition of ACS?

3. Classification (think simple… ACS/NSTEMI vs. STEMI)

4. Sick or not sick (i.e. cath lab/thrombolytics fast?)

5. Management

What is ACS?

ACS = Unstable angina / NSTEMI/ STEMI

Pathophysiology

Stable USA NSTEMI STEMIAngina

Fixed Plaque Plaque OccludingPlaque Rupture Rupture Thrombus + + Evidence of Myocardial Myocardial Damage Damage

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

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

Recognition of ACS

Markers of Myocardial Injury:

1. USA: with ischemic symptoms suggestive of an ACS and no elevation in troponins or CK-MB, with or without ECG changes

2. NSTEMI: same manifestations as those in USA, but in whom an elevation in troponins or CK-MB is present

3. STEMI: ischemic symptoms; ST elevations or pathologic Q waves; elevated troponins or CK-MB

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)

Recognition Triage (sick vs. not sick)

Sick:

1. 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

Recognition Triage (sick vs. not sick)

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

Recognition Triage (sick vs. not sick)

Sick:

3. Refractory chest pain:

If good story, elevated markers, suggestive ECG changes:

Triage cath lab

Management

Sick cath vs lytics if STEMI

STEMI cath vs. lytics

USA/NSTEMI medical management plus reperfusion (PCI)

USA/NSTEMI: Goals of Therapy

1. Relief of ischemic pain2. Assessment of hemodynamic state and

correction of abnormalities3. Antithrombotic therapy:

-prevent further thrombosis and progression to STEMI-prevent embolization of plaque

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

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

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

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

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

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

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)

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)

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

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

USA/NSTEMI: beta blockers

Decrease death by 20-30% Do not use in symptomatic bradycardia; high

degree AV block; decompensated CHF; hypotension

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

USA/NSTEMI: Further Medical Management

ARBs

-limited data

-probably should not use combination of ACE-I and ARB (VALIANT trial)

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

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

USA/NSTEMI: Should NOT GET…

Prophylactic antiarrhythmics Digoxin CCB

STEMI: Quick Recognition!!!

- Story- ECG- Serum cardiac enzyme elevation

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

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

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

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

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

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

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

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

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

STEMI: Medical Therapy

Nitro ggt Beta Blockers K and Mg repletion:

HypoK in AMI: risk for VF Glucose control

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)

STEMI: Further Medical Management

Repeat reperfusion therapy ACE Inhibitors ARB Statin therapy Aldosterone Antagonists Risk stratification

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

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