Management of Acute Coronary Syndrome

Lavina Belayutham

Unstable Angina (UA) and

Non-ST-Segment Elevation Myocardial Infarction (NSTEMI)

• Factors associated with ACS:

a) prior history of stable angina

b)history of established CAD by angiography

c)prior MI

d)CHF

e)new ECG changes

f)elevated cardiac biomarkers

Diagnostic Pathway

Risk Stratification and Prognosis

Treatment of UA/NSTEMI

Medical Treatment• Bed rest with continuous ECG monitoring• Ambulation permitted if the patient shows no

recurrence of ischemia (discomfort or ECG changes) and does not develop a biomarker of necrosis for 12–24 hours

Anti-ischemic TreatmentNitratesDosage :• Sublingually (0.3 to 0.6 mg)• If pain persists after 3 doses given 5 min apart, iv

nitroglycerin 5–10 µg/min- Rate of infusion may be increased by 10µg/min every 3-5 min until symptoms are relieved or systolic arterial pressure falls to <100mmHg

When to avoid :a) Hypotensionb) Patient receiving sildenafil or other PDE-5

inhibitor within the previous 24-48 hours

Beta blockersClinical condition : Unstable anginaDosage :• Metoprolol 25–50 mg orally every 6 hours• IV administrationWhen to avoid : a) PR interval (ECG) >0.24 sb)Heart rate <60 beats/minc)Systolic pressure <90 mmHgd)Shocke)Left ventricular failure f)Severe reactive airway disease

Calcium channel blockersClinical condition : Patients whose symptoms

are not relieved by adequate doses of nitrates and beta blockers, or in patients unable to tolerate adequate doses of one or both of these agents

When to avoid :a)Pulmonary edemab)Evidence of left ventricular dysfunction (for

diltiazem or verapamil)Dosage :Dependent on specific agent

Morphine SulphateClinical Condition : Patients whose symptoms are

not relieved after three serial sublingual nitroglycerin tablets or whose symptoms recur with adequate anti-ischemic therapy

When to avoid :a)Hypotensionb)Respiratory depressionc)Confusion Dosage :• 2–5 mg IV dose• May be repeated every 5–30 min as needed to

relieve symptoms and maintain patient comfort

Antiplatelet AgentsOral Antiplatelet Therapy

Aspirin Initial dose of 162–325 mg nonenteric formulation followed by 75–162 mg/day of an enteric or a nonenteric formulation

Clopidogrel Loading dose of 300-600 mg followed by 75 mg/day

Prasugrel Pre-PCI: Loading dose 60 mg followed by 10 mg/day

Intravenous Antiplatelet Therapy

Abciximab 0.25 mg/kg bolus followed by infusion of 0.125µ g/kg per min (maximum 10µ g/min) for 12 to 24 hour

Eptifibatide 180µ g/kg bolus followed by infusion of 2.0µ g/kg per min for 72 to 96 hour

Tirofiban 0.4µ g/kg per min for 30 min followed by infusion of 0.1µ g/kg per min for 48 to 96 hour

Combination of clopidogrel and aspirin - Clopidogrel combined with aspirin – reduce cardiovascular

death, MI, or stroke- Pretreatment with clopidogrel (300 or 600 mg loading dose,

followed by 75 mg qid) recommended prior to PCI- Clopidogrel may cause increase in major bleeding- Should be continued for 1 year

Prasugrel - Considered if hyporesponsive to clopidogrel- More rapid onset- Higher level of platelet inhibition- Prior to PCI (60 mg loading dose followed by 10 mg/day for up

to 15 months)- Contraindication : prior stroke or TIA

Ticagrelor- Reversible ADP inhibitor- Reduced mortality- Doesn’t increase the risk of total bleeding

Intravenous GP IIb/IIIa inhibitors

-Small reduction in death or MI

-Significant increase in major bleeding

-Unstable patients with recurrent rest pain and ECG changes who undergo PCI

AnticoagulantsHeparins  

Unfractionated Heparin (UFH) Bolus 60–70 U/kg (maximum 5000 U) IV followed by infusion of 12–15 U/kg per hour (initial maximum 1000 U/hour) titrated to a PTT 50–70 second

Enoxaparin 1 mg/kg SC every 12 hour; the first dose may be preceded by a 30-mg IV bolus; renal adjustment to 1 mg/kg once daily if creatine Cl < 30 cc/min

Fondaparinux 2.5 mg SC qid

Bivalirudin Initial bolus intravenous bolus of 0.1 mg/kg and an infusion of 0.25 mg/kg per hour. Before PCI, an additional intravenous bolus of 0.5 mg/kg was administered, and the infusion was increased to 1.75 mg/kg per hour.

Invasive vs Conservative Strategy

• early invasive strategy- high-risk patients• following treatment with anti-ischemic and

antithrombotic agents, coronary angiography carried out within 48 hours of admission, followed by coronary revascularization (PCI or CABG )

• low risk patients - conservative strategy - anti-ischemic, antithrombotic therapy and wait

-coronary angiography if :a) rest pain or ST-segment changes recur b)evidence of ischemia(stress test)

Early Invasive StrategyClass I (Level of Evidence: A) Indications 

Recurrent angina at rest/low-level activity despite Rx

Elevated TnT or TnI

New ST-segment depression

Rec. angina/ischemia with CHF symptoms, rales, MR

Positive stress test

EF < 0.40

Decreased BP

Sustained VT

PCI < 6 months, prior CABG

Percutaneous Coronary Intervention (PCI)

Coronary Artery Bypass Grafting (CABG)

Long Term Management• Risk factor modification• Drugs :

a)Beta blockers, statins (at a high dose) and ACE inhibitors or angiotensin receptor blockers

b)Combination of aspirin and clopidogrel for 1 year, aspirin continued thereafter (reduces severity of thrombosis if a plaque ruptures)

Treatment of ST-Segment Elevation Myocardial Infarction

(STEMI)

Initial Management

Prehospital Care

Management in the Emergency Department

• Aspirin

- 160–325mg tablet (buccal absorption)

- daily oral administration (75–162 mg)

• Hypoxemia - O2 (2–4 L/min) first 6–12 hour after infarction

Control of discomfort

• Sublingual nitroglycerin - Up to three doses- If chest discomfort returns with evidence of

ongoing ischemia – intravenous nitroglycerin

• Morphine - Every 5 min intravenous injection of small doses

(2-4mg)- Reduce arterial pressure (elevation of legs,

volume expansion with intravenous saline)

• Intravenous beta blockers

- Diminish myocardial oxygen demand - Reduce reinfarction and ventricular fibrillation- Oral beta blockers initiated in the first 24 hours for

patients who do not have :

a)signs of heart failure

b)evidence of low output state

c)increased risk for cardiogenic shock

d)others- metoprolol, 5 mg every 2–5 min for a total of 3 doses- 15 minutes after the last intravenous dose, oral regimen is

initiated (50 mg every 6 hours for 48 hours, followed by 100 mg every 12 hours

Management Strategies

Primary Percutaneous Coronary Intervention

• Angioplasty and/or stenting without preceding fibrinolysis

• More effective, better short term and long term clinical outcomes(performed by experienced operators and dedicated medical centers)

• When primary pci is preferred :- diagnosis is in doubt- cardiogenic shock - bleeding risk increased- symptoms have been present for at least 2–3 hours

Fibrinolysis• Ideally within 30 min of presentation• Remains of benefit 3–6 hour, some benefit up to

12 hour (chest discomfort still present and ST segments remain elevated)

• Fibrinolytic agents approved for iv use : a)tissue plasminogen activator (tPA)b)streptokinasec) tenecteplase (TNK) d)reteplase (rPA)• Promote conversion of plasminogen to plasmin• TNK and rPA : bolus fibrinolytics ( administration

doesn’t require a prolonged iv infusion)

Thrombolysis In Myocardial Infarction (TIMI) Grading System

• grade 0: complete occlusion of the infarct-related artery• grade 1: some penetration of the contrast material beyond

the point of obstruction but without perfusion of the distal coronary bed

• grade 2: perfusion of the entire infarct vessel into the distal bed, but with flow that is delayed compared with that of a normal artery

• and grade 3: full perfusion of the infarct vessel with normal flow

- goal of reperfusion therapy : grade 3

TIMI Frame Count

Counting the number of frame on the cine film required for dye to flow from the infarct-related artery to a landmark in the distal vascular bed

TIMI Myocardial Perfussion Rate

Determining the rate of entry and exit of contrast dye from the microvasculature in the myocardial infarct zone

• reduce infarct size, limit LV dysfunction, reduce the incidence of serious complications (e.g.cardiogenic shock)

• preferred reperfusion strategy for patients presenting in the first hour of symptoms if:

a) there are logistical concerns about transportation of the patient to a suitable PCI center

b) there is an anticipated delay of at least 1 hour between the time that fibrinolysis could be started versus implementation of PCI

Regimens

tPA :15mg bolus followed by 50 mg intravenously first 30 min, followed by 35 mg next 60 min

Streptokinase : 1.5 million units (MU) intravenously over 1 hour

rPA : double-bolus regimen consisting of a 10-MU bolus given over 2–3 min, followed by a second 10-MU bolus 30 min later

TNK : single intravenous bolus of 0.53 mg/kg over 10 seconds

Alternative Pharmacologic Regimen

1.iv gp IIb/IIIa inhibitor + reduced dose of fibrinolytic agent

- facilitate fibrinolysis (penetration deeper into the clot)

- increased risk of bleeding, especially in patients >75 years (not recommended for routine use)

- similar efficacy as bolus fibrinolytics

Integrated Reperfusion Strategy

Contraindications

Clear contraindications a) history of cerebrovascular hemorrhage at any timeb) a nonhemorrhagic stroke or other cerebrovascular

event within the past yearc) marked hypertension (systolic arterial pressure >180

mmHg and/or a diastolic pressure >110 mmHg) at any time during the acute presentation

d) suspicion of aortic dissectione) active internal bleeding (excluding menses)

Relative contraindications

a) current use of anticoagulants

b)recent (<2 weeks) invasive or surgical procedure

c) prolonged (>10 min) cardiopulmonary resuscitation

d)known bleeding diathesis

e)pregnancy

f) hemorrhagic ophthalmic condition

g) active peptic ulcer disease

h)history of severe hypertension that is currently adequately controlled

Complications

• Hemorrhagic stroke- most serious complication• Allergic reactions to streptokinase

• Cardiac catheterization and coronary angiography after fibrinolytic therapy if:

a) failure of reperfusion (persistent chest pain and ST-segment elevation >90 min) – rescue PCI

b) coronary artery reocclusion (re-elevation of ST segments and/or recurrent chest pain) or the development of recurrent ischemia – urgent PCI

• Coronary artery bypass surgery -coronary anatomy is not suitable for PCI , revascularization advisable

Hospital Phase Management

Coronary Care Units• continuous monitoring of cardiac rhythm,

hemodynamic monitoring Activity• bed rest for the first 12 hours• upright posture, dangling their feet over the side of the

bed, sitting in a chair within the first 24 h• ambulating in their room with increasing duration and

frequency (second or third day)• increasing their ambulation progressively to a goal of

185 m (600 ft) at least 3 times a day ( by day 3)

Diet • either nothing or only clear liquids by mouth for the first 4–12

hours• diet provide 30% of total calories as fat, have a cholesterol

content of 300 mg/d. Complex carbohydrates –( 50–55% of total calories). Menu should be enriched with foods that are high in potassium, magnesium, and fiber, but low in sodium

Bowel Management• bedside commode, a diet rich in bulk, use of a stool softener

(dioctyl sodium sulfosuccinate 200 mg/day) • laxative

Sedations• Diazepam (5 mg), oxazepam (15–30 mg), or lorazepam (0.5–2

mg), given 3–4 times daily

Pharmacotherapy

Antithrombotic Agents• Aspirin + P2Y12 inhibitor (reduce risk of stroke,

reinfarction, death)• Glycoprotein IIb/IIIa receptor inhibitors

(prevent thrombotic complication in patient undergoing PCI)• Aspirin + non-fibrin-specific-thrombolytic agent + UFH –

additional mortality benefits (about 5 lives saved per 1000 patient treated)

• Dose of UFH : initial bolus of 60 U/kg (maximum 4000 U) followed by an initial infusion of 12 U/kg per hour (maximum 1000 U/h). aPTT during maintenance therapy should be 1.5–2 times the control value.

• Alternatives to UFH : fondaparinux, bivalirudin• Patients at risk of systemic or pulmonary

thromboembolism:a) anterior location of the infarctionb) severe LV dysfunctionc) heart failured) history of embolisme) two-dimensional echocardiographic evidence of

mural thrombusf) atrial fibrillation - Full therapeutic levels of anticoagulant therapy

(LMWH or UFH) while hospitalized, followed by at least 3 months of warfarin therapy

Beta- blockers• acute intravenous beta blockade decreases pain,

reduces infarct size, decreases the incidence of serious ventricular arrhythmias

• In patients who undergo fibrinolysis - recurrent ischemia and reinfarction reduced

Inhibition of the Renin- Angiotensin – Aldosterone System

• ACE inhibitors -maximum benefit in high risk patients :-elderly-anterior infarction-prior infarction-depressed LV function

• reduction in ventricular remodeling after infarction - reduction in risk of CHF

• ARB (intolerant to ACE inhibitors)• continued in patients with clinically evident

CHF, reduction in LV function, hypertensive

Thank You!