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Acute Coronary Syndromes; The Nuts and Bolts

Michael P. Gulseth, Pharm. D., BCPSPharmacotherapy II

Spring 2006

Objectives• Compare and contrast pathophysiology of unstable

angina (UA), non-ST segment elevation MI (NSTEMI), and ST segment elevation MI (STEMI)

• Identify how the specific diagnosis of MI is made• Identify “high risk” markers in patients with UA or

NSTEMI• List the two reperfusion strategies used to treat patients

with STEMI• List the two reperfusion strategies usually employed

early for high risk UA or NSTEMI patients

Overview

• Cardiovascular disease (CVD) is the #1 killer of Americans

• The most common cause of CVD death are the acute coronary syndromes

• Every year 1 million Americans will experience ACS; 239,000 will die of an MI

• The cause of ACS is the rupture of a atherosclerotic plaque and subsequent activation of platelets and the clotting cascade

Quick quiz…..

• Based on the little we have just talked about, what would be logical medication choices to treat these patients?

Any guesses as to risk factors of developing these plaques?

• Hypertension• Male gender• Tobacco use• DM• Obesity• Elevated homocysteine• Dyslipidemia

How dose the plaque start?• The earliest stage is called endothelial

dysfunction– Starts early in life and characterized by:

• Imbalance between vasocontricting and vasodilating substances leading to vascular reactivity

• Imbalance of procoagulant and anticoagulant molecules; promotes platelet aggregation and thrombus formation

• Increase expression of leukocyte adhesion molecules that attract inflammatory cells in the vessel wall

• Permeability to LDL cholesterol and inflammatory cells is increased and deposit in the subintimal vessel wall

• Leads to fatty streaks and eventual plaque formation

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Atherosclerosis TimelineAtherosclerosis TimelineFoamFoamCells Cells

FattyFattyStreak Streak

IntermediateIntermediateLesion Lesion AtheromaAtheroma

FibrousFibrousPlaquePlaque

ComplicatedComplicatedLesion/Lesion/RuptureRupture

Adapted from Pepine CJ. Am J Cardiol. 1998;82(suppl 104).

From FirstDecade

From ThirdDecade

From FourthDecade

Endothelial DysfunctionEndothelial Dysfunction

ACS Spectrum• ACS is “catch all” of conditions that lead to acute

myocardial ischemia– From an imbalance between myocardial O2 supply

and demand– Due to an occlusive or partially occlusive coronary

artery thrombus due to a plaque rupture• ACS is categorized via the ECG changes seen• NSTEMI is different than UA in that the ischemia

was bad enough to cause necrosis leading to myocite release of biochemical markers like troponin and creatine kinase

Spectrum of Acute Coronary Syndrome

Ischemic DiscomfortUnstable Symptoms

No ST-segmentelevation

ST-segmentelevation

Unstable NSTEMI STEMIAngina (Non-Q MI) (Q-wave MI)

ECG(10 min)

Cardiac Biomarkers

HistoryPhysical Exam

(positive cardiac biomarker)

STEMI ECGA. Normal ECG prior to MI

B. Hyperacute T wave changes –increased T wave amplitude and width; may also see ST elevation

C. Marked ST elevation with hyperacute T wave changes (transmural injury)

D. Pathologic Q waves, less ST elevation, terminal T wave inversion (necrosis) (Pathologic Q waves are usually defined as duration >0.04 s or >25% of R-wave amplitude)

E. Pathologic Q waves, T wave inversion (necrosis and fibrosis)

F. Pathologic Q waves, upright T waves (fibrosis)

NSTEMI ECG

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““Warning Arrhythmias”Warning Arrhythmias”

Antman and Rutherford. Coronary Care Medicine. Boston, MA: Martinus Nijhoff Publishing;1986:81.

What happens to start an episode of ACS?

• Begins with rupture, fissuring, or erosion on an unstable plaque– Usually plaques of < 50% when this occurs

• Clots form due to the exposure of collagen and tissue factor– Causes platelet adhesion and activation– Also activates the clotting cascade

• Thrombis can be partially or totally occlusive– Which ACS condition would result from each of the

above?

Chronology of the interface between the patient and the clinician through the progression of plaque formation and the onset of complications of STEMI.

Management Before STEMI

41 2 3 4 5 6

Onset of STEMI- Prehospital issues- Initial recognition and management in the Emergency Department (ED)

- Reperfusion

Hospital Management- Medications- Arrhythmias- Complications- Preparation for discharge

Secondary Prevention/Long-Term Management

Presentation

Working Dx

ECG

Cardiac Biomarker

Final Dx

UA

NQMI QwMI

No ST Elevation

NSTEMI

Ischemic DiscomfortAcute Coronary Syndrome

UnstableAngina

Myocardial Infarction

ST Elevation

Modified from Libby. Circulation 2001;104:365, Hamm et al. The Lancet 2001;358:1533 and Davies. Heart 2000;83:361. Thrombus Formation

Red cells

Fibrin

Plaque rupture

Platelets

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Now, about those clots…..

• Thrombus that have more platelets than fibrin have a white appearance– “White clots”– More common in UA and NTEMI– Myocardial ischemia also occurs due to downstream

embolism of microthrombi• STEMI patients have a completely occluded

lumen and contain much more fibrin and red blood cells and smaller amounts of platelets– “Red clot”

Ventricular Remodeling• Occurs in some cardiovascular conditions

– Heart failure– MI

• Left ventricle changes in size, shape, and function– Leads to heart failure– Want to prevent this– Caused by upregulation of the renin-angiotensin-aldosterone

system (RAS), sympathetic nervous system, other hemodynamic factors, mechanical factors, changes in gene expression

– All of this promotes both systolic and diastolic dysfuntion• Based on the upregulation of the RAS and sympathetic

nervous system, what agents could help prevent this process?

What are the complications of MI?

• Cardiogenic shock• Heart failure• Valvular dysfunction• Ventricular and atrial

arrhythmias• Bradycardia• Heart block

• Pericarditis• Stroke due to left

ventricle thrombus embolization

• Venous thromboembolism

• Left ventricle rupture

Presentation

• See Table 16-1 in your text• ECG needs to be obtained to risk stratify

the ACS being experienced– Usually compared to an old ECG– Looking for ST-elevation or depression, T

wave inversion– Depending on leads and where changes are

see, this can help identify which artery is involved

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Biochemical Markers

• Biochemical markers are used to confirm the diagnosis of MI– Released when myocardial cells die

• Blood is obtained three times over 12-24 hours

• Need at least one positive troponins or two positive CK MB to confirm diagnosis of MI– Troponins stay elevated for up to 10 days

Risk Stratification• Patient symptoms, past medication history,

ECG, and biochemical markers are used together to stratify risk for each patient

• Since complete occlusion, STEMI patients require immediate revascularization– Done with lytics or a primary PCI– Lytics should be given within 30 minutes of

presentation– Balloon inflation with primary PCI must occur within

90 minutes– “The sooner the better”

Risk Stratification for UA/NSTEMI

• Not the same type of emergency that STEMI is

• TIMI risk scoring is useful for these patients

TIMI Risk

• Low Risk– 0-2 points

• Medium Risk– 3-4 points

• High Risk– 5-7 points

• TIMI is not always used in actual practice to define risk, however, it gives a students a good idea who is higher risk

UA/NSTEMI Treatment/Low Risk

• Evaluated in the ER with serial biochemical markers

• If negative, usually admitted to the floor with telemetry and may undergo a stress test

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UA/NSTEMI TreatmentMedium-High Risk

• Admitted to hospital; could go to coronary intensive care, chest pain unit, or general floor based on perceived risk

• High risk patient will also undergo “early” PCI and revascularization if stenosis is found

• Moderate risk patients with MI will also typically go for PCI and revascularization during hospital stay

• Moderate risk patients without MI may have a stress test before PCI

• Much of the pharmacotherapy is dictated by risk stratification and the plan of action

Other General Treatments of ACS

• All STEMI and medium to high risk NSTEMI patients get:– Admitted to hospital– O2 if saturations are low– Continuous telemetry monitoring– Frequent vital sign checks– Best rest for 12 hours– Stool softeners– Pain relief

Revascularization

• STEMI– Primary PCI in 90 minutes (preferred) or if

lytics contraindicated– Lytics

• UA/NSTEMI– PCI– CABG– These are usually within 24 hours for medium

to high risk patients

PCI with stent• Catheter is inserted in

groin in femoral artery• Catheter is threaded to

aorta dye is infused into the heart chambers

• “Lights up” the coronary arteries on X-ray and lesions can be detected

• Problem lesions are then stented

Fibrinolytics

• Are simply boring drugs

• “Clot busters”• Activate plasminogen

to plasmin

CABG

• Artery is taken from your chest or leg– Internal mammary– Saphenous– Radial

• One end is attached to the aorta and the other to a point below the “clog”

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Conclusion• ACS results from clot formation on a ruptured coronary

artery• STEMI results when the coronary artery is completely

occluded• UA/NSTEMI result when the occlusion in incomplete• The MI diagnosis is confirmed by positive biochemical

markers• TIMI risk stratification can be helpful to risk stratify

UA/NSTEMI patients• STEMI patients must be quickly revascularized with

primary PCI or lytic therapy• Medium to high risk UA or NSTEMI patients typically

undergo PCI or CABG

Review Questions• What event starts on episode of ACS?• In a NSTEMI event, is the occlusion complete or

partial? STEMI?• What diagnostic markers are used to diagnose

an MI?• What are “high risk” markers in patients with

UA/NSTEMI, and how does this relate to therapy?

• What are the two general reperfusion strategies employed in UA/STEMI? STEMI?