ST-Elevation Myocardial Infarction

Tauhid Ahmed Bhuiyan, PharmDPGY-1 ResidentKing Faisal Specialist and Research Center (KFSH&RC)

ST-ELEVATION MYOCARDIAL INFARCTION (STEMI): A TOPIC REVIEW AND CASE PRESENTATION

King Faisal Specialist Hospital and Research Center (KFSHRC) is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. (UAN# 0833-0000-14-064-L01-P, 0833-0000-14-064-L01-T)

http://www.acpe-accredit.org/pdfwebtool/Common/images/logo/ACPE_489_469.jpg

OBJECTIVES• Provide an overview of STEMI in terms of epidemiology, etiology,

pathophysiology, and risk factors

• Identify key diagnostic criteria to diagnose STEMI

• Review current guideline directed standard of care in the management of STEMI

• Analyze a patient case related to the topic

I do not have financial relationship and no actual or potential conflict of interest in relation to this activity

BACKGROUND • STEMI:

– An acute coronary event that results in complete occlusion of the coronary artery Myocardial Ischemia

• Myocardial infarction (MI) is the manifestation of prolonged ischemic event

• Ischemia is associated with – Persistent ST segment elevation on electrocardiography (ECG)– Release of cardiac biomarkers of myocardial necrosis

• Emergency requiring immediate medical intervention

SPECTRUM OF ACUTE CORONARY SYNDROME

Fox K. Heart 2004; 90:698-706

EPIDEMIOLOGY• Estimated annual incidence of myocardial infarction (MI) in the

United States:– New: 565 K– Repeat: 300 K

• STEMI accounts for 30%-40%

– ~20%-30% patients die before reaching to the hospital

– In-hospital and 30-day mortality rates have been estimated to be 8.8% and 18.4%, respectively

O’Gara PT et al. Circulation; 2013; 127

KINGDOM OF SAUDI ARABIA

• Osman et al. conducted a prospective observational trial of 205 patients at Prince Sultan Cardiac Center in Riyadh, Saudi Arabia

– STEMI accounted for 19.5% of diagnosis at admission and has the highest direct medical cost (58K SAR/patient)

• Gulf RACE – 2 study by AlHabib et al:– 9 month prospective, multicenter study – Evaluated data on patients with acute coronary syndromes and their long term

outcomes in the Arabian Gulf countries– STEMI accounted for 45.6% of the cases (N=7930)

Osman AM et al. Saudi Med J; 2011; 32(12):1279-84Alhabib KF et al. Ann Saudi Med; 2012; 32(2):9-18

ETIOLOGY

• Most common: Atherosclerotic disease

• Less common: Coronary embolism Coronary vasospasm (e.g. prinzmetal’s angina) Drug induced (e.g. cocaine, chemotherapeutic agents) Spontaneous coronary dissection or aortic dissection

CORONARY CIRCULATION

• Originates from the aorta

• Right coronary artery bifurcates into:• Right marginal artery• Posterior descending artery

• Left coronary artery bifurcates into:• Left anterior descending artery (LAD)• Circumflex artery

http://labelled-diagram-of-the-human-heart.blogspot.com/2009/07/coronary-arteries.html

PATHOPHYSIOLOGY

Rupture of “vulnerable” atherosclerotic plaque

Activation of coagulation cascade and fibrin deposition

Partial (NSTMI) or totally occlusive (STEMI) coronary vessel

Myocardial ischemia and necrosis

http://pmtwww.uptodate.com/contents/image?imageKey=PI/60394&topicKey=PI%2F3428&source=outline_link

COAGULATION CASCADE

http://openi.nlm.nih.gov/imgs/512/349/2496975/2496975_vhrm0402-305-01.png

RISK FACTORS

Non-modifiable

AgeGender Family history of

atherosclerotic coronary artery disease

Modifiable

HyperlipidemiaDiabetes MellitusHypertension Tobacco use

Bolooki MH et al. Acute Myocardial Infarction. Available at: http://www.clevelandclinicmeded.com

http://www.clevelandclinicmeded.com/

EARLY RISK ASSESSMENTS

• Global Registry of Acute Coronary Event (GRACE) risk score:– Predicts in-hospital and 6-months mortality rate– http://www.outcomes-umassmed.org/grace/acs_risk/acs_risk_content.h

tml

• Thrombolysis In Myocardial Infarction (TIMI) risk score:– Estimates overall mortality of STEMI– http://www.mdcalc.com/timi-risk-score-for-stemi/


http://www.outcomes-umassmed.org/grace/acs_risk/acs_risk_content.html

http://www.outcomes-umassmed.org/grace/acs_risk/acs_risk_content.html

http://www.mdcalc.com/timi-risk-score-for-stemi/

CLINICAL PRESENTATION • Differ by gender and age

• Midline anterior and/or retrosternal chest pain/discomfort lasting >20 minutes in duration– May radiate to shoulder, arm, back, jaw– Unremitting – May describes as pressure sensation, fullness, or heaviness– Associated symptoms: nausea and vomiting, palpitations, diaphoresis or sweating, dyspnea or

shortness of breath, cough, syncope, or low grade fever

• Patient may present with acute heart failure, tachycardia, bradycardia, or heart block

• Hypotension or cerebrovascular symptoms in elderly

Koda-Kimble MA et al. Myocardial Infarction. In: Applied Therapeutics: The Clinical Use of Drugs, 2009

DIAGNOSIS

CLASSIC TRIAD

Ischemic symptoms

ECG changesRelease of

cardiac biomarkers

• New ST-elevation at the J point (at least 2 contiguous leads):– ≥ 2 mm (0.2 mV) in men– ≥ 1.5 mm(0.15 mV) in women

OR– ≥ 1 mm (0.1 mV) in other contiguous chest leads or limb leads

• ST-depression:– ≥ 2 precordial leads (V1 – V4): may indicate transmural posterior injury

• Established MI– Presence of Q waves of ≥ 0.03 s in leads V1 – V6 or II, aVL, aVF

12-LEAD ELECTROCARDIOGRAM (ECG)

V2 – V3


LOCATION OF MI

http://imgarcade.com/1/septal-mi/

LABORATORY MARKERS• Biomarkers

– CK • Less specific for cardiac muscle necrosis

– CK-MB• Detectable within 6 hours, falls within

48 hours

– Troponin I or T• Detectable within 6 hours, remains

elevated for 7-14 daysDiPiro J. Acute Coronary Syndrome. In: Pharmacotherapy: A Pathophysiological Approach, 2011

COMPLICATIONS OF MI

Ventricular remodelingCardiogenic shockDeathValvular dysfunctionArrhythmias (VF/VT)Heart failure

BradycardiaHeart blockPericarditisCVA secondary to LV

thrombusFree wall rupture (e.g. VSD,

papillary muscle dysfunction)

DiPiro J. Acute Coronary Syndrome. In: Pharmacotherapy: A Pathophysiological Approach, 2011

MANAGEMENT

GOALS OF THERAPY• Short term:

– Early restoration of epicardial blood flow and myocardial perfusion in the infarct zone

– Relief ischemic chest discomfort and restoration of ECG changes

• Long term:– Prevent death or MI complications– Prevent reocclusion or reinfarction


ACC/AHA CLASSIFICATION OF RECOMMENDATIONS


MANAGEMENT

Reperfusion Therapy

Pharmacological

Non-Pharmacological

REPERFUSION THERAPY

• Prompt and effective reperfusion therapy is the cornerstone for treatment of STEMI

• Selection of reperfusion depends on chance of achieving early and persistent reperfusion with lowest risk of major complications

• Guideline recommendation:– Should be administered to all eligible patients with STEMI with symptoms onset within

the prior 12 hours(Class 1; LOE: A) – 12-24 hours for patient with ongoing ischemia (Class IIa; LOE: B)


TYPES OF REPERFUSION

Primary Percutaneous Coronary Intervention (PPCI) Fibrinolytics

Balloon angiography 1. Strptokinase 2. Alteplase 3. Reteplase 4. Tenecteplase Placement of intracoronary stent:

Bare-metal stent (BMS) Drug-eluting stent (DES)



Rescue PCI

PCI: percutaneous coronary interventionFMC: first medical contactCABG: coronary artery bypass graft

ALGORITHM OF THERAPY

TIMING TO REPERFUSION THERAPY

Treatment Recommended Time for Initiation of Treatment

PCI Door-to-balloon time ≤ 90 min

Fibrinolytic agents

Door-to-needle time ≤ 30 min

Hilleman DE et al. Pharmacotherapy. 2007;27(11):1558-1570

PRIMARY PCI (PPCI)

http://www.youtube.com/watch?v=S9AqBd4RExk

http://www.youtube.com/watch?v=S9AqBd4RExk

PPCI• Indications:

ACC/AHA Recommendations COR† LOE†1. Ischemic symptoms <12 h I A

2. Ischemic symptoms <12 h and contraindications to fibrinolytic therapy irrespective of time delay from FMC

I B

3. Cardiogenic shock or acute severe HF irrespective of time delay from MI onset

I B

4. Evidence of ongoing ischemia 12 to 24 h after symptom onset IIA B

5. PCI of a non-infarct artery at the time of primary PCI in patients without hemodynamic compromise III: Harm B

COR: Classification of recommendation; LOE: level of evidence


PPCI >>> FIBRINOLYTICS

• Greatest survival benefit in high risk patient

• Higher rates of infarct artery patency with TIMI 3 flow (90%-PCI vs. <60%-fibrinolysis)

• Reduction in recurrent ischemia/reinfarction

• 30-day mortality reduction (6.5% to 4.4%)

• Reduction in stroke (2.0% to 0.7%)

• Reduced risk of bleeding

Van De Wefr F. et al. Circulation. 2002;105: 2813-16O’Gara PT et al. Circulation; 2013; 127

TIMI Flow Grade

Characteristics

0 No perfusion

1Penetration without perfusion

2Partial reperfusion

3Complete perfusion

TIMI: Thrombolysis in Myocardial Infarction

FIBRINOLYTIC THERAPY

• Acts on converting plasminogen to plasmin cleaves fibrin causing clot dissolution and restoration of blood flow

• Indications:

Recommendations COR† LOE†1. Ischemic symptoms <12 h I A

2. Evidence of ongoing ischemia 12 to 24 h after symptom onset and a large area of myocardium at risk or hemodynamic instability IIa C

3. ST depression, except if true posterior MI is suspected or when associated with ST elevation in lead aVR III: Harm B

O’Gara PT et al. Circulation; 2013; 127Hilleman DE et al. Pharmacotherapy. 2007;27(11):1558-1570

CHOICE OF FIBRINOLYTIC AGENTS• Adjunctive antiplatelet and/or anticoagulant therapies are

indicated, regardless of the choice of fibrinolytic agent

Agents Fibrin Specificity Half-life (h) Patency Rate

Alteplase (tPA)(Activase®)

++ 5 73%-84%

Reteplase (rPA)(Retavase®)

++ 13-16 84%

Tenecteplase (TNKase®)

++++ 20-24 85%

Streptokinase(Streptase®)

No 18-23 60%-68%

EFFICACY AND SAFETY DATA


DOSE AND ADMINISTRATION

Agents Dose and Administration

Alteplase (tPA)*

90 min infusion: • 15 mg bolus, then • Infusion 0.75 mg/kg for 30 min (max 50 mg), then 0.5 mg (max 35 mg) over the next 60 min; total dose not to exceed 100 mg; 60 mg administered within first hour, then 20 mg during second and third hour

Reteplase (rPA) Two 10 unit boluses, each administered over 2 min, 30 min apart

Tenecteplase (TNK)

Single bolus administration over 5 sec; dose based on patient weight (max dose 50 mg): <60 kg: 30 mg; 60-69 kg: 35 mg; 70-79 kg: 40 mg; 80-89 kg: 45 mg; and ≥ 90 kg: 50 mg

Streptokinase 1,500,000 units IV infusion over 30-60 min


*KFSH&RC formulary

CONTRAINDICATIONS TO FIBRINOLYTIC THERAPY


ADJUVANT THERAPIES

DUAL ANTIPLATELET THERAPY/DAPT

PLATELET ACTIVATION AND MECHANISMS OF ADVERSE CLINICAL OUTCOME

Alexopoulos D. Int J Card; 2013; 163:249-55

ASPIRIN

• Irreversibly inhibits cyclooxygenase-1 and 2 enzymes decreased formation of prostaglandin and thromboxane A2 inhibit platelet aggregation

ACC/AHA Recommendations

PPCI 162-325 mg loading dose (IB) followed by ASA 81 mg daily (indefinitely) (IA)

Fibrinolysis162-325 mg loading dose (IA) followed by ASA 81 mg daily (indefinitely) (IA)


THIENOPYRIDINES• Prevents P2Y12 component of ADP receptors on the platelet surface

blocking activation of GPIIb/IIIa receptor complex, thereby reduce platelet aggregation

ACC/AHA Recommendations

PPCI:1. Clopidogrel: 600 mg PO as early as possible or at the time of PCI (IB) followed by 75 mg daily (IB)2. Prasugrel: 60 mg as early as possible or at the time of PCI (IB) followed by 10 mg daily (IB) 3. Ticagrelor: 180 mg as early as possible or at the time of PCI (IB) followed by 90 mg twice a day[Note: maintenance therapy continue for 1 year for both BMS/DES ; dose of ASA should not exceed 100 mg with

ticagrelor as DAPT]

Fibrinolytics:1. Clopidogrel:

a. Age ≤ 75 years: 300 mg loading dose (IA) followed by 75 mg daily for at least 14 days (IA) to 1 year in absence of bleeding (IC)

b. Age >75 year: 75 mg once (IA) then daily for at least 14 days (IA) up to 1 year (IC) in absence of bleeding


COMPARATIVE ADVANTAGE/DISADVANTAGE

Agents Characteristics ContraindicationsOnset

of Action

Potency Variable

Response

Clopidogrel(Plavix®)

Produrg, binds irreversibly

Hypersensitivity, active pathological bleeding ++ + ++++

Prasugrel (Effient®)

Produrg, binds irreversibly

Hypersensitivity, active pathological bleeding, prior TIA or stroke, age ≥ 75 years or body weight <60 kg

++++ +++ �

Ticagrelor(Brilinta®)

Nonthienopyridine, reversible binding

Hypersensitivity, active pathological bleeding , severe hepatic impairment

++++ +++ �


MAJOR TRIALS—OUTCOME COMPARISON


ANTICOAGULATION THERAPY

Caterina RD et al. Thromb Haemost; 2013; 109:769-86

PPCIACC/AHA Recommendations

Unfactionated Heparin (UFH)• With GP IIb/IIIa receptor antagonist planned: 50-70 U/kg IV bolus to

achieve ACT (IC)• With no GP IIb/IIIa receptor antagonist planned: 70-100 U/kg IV

bolus to achieve ACT (IC)

Bivalirudin (preferred over UFH in high bleeding risk patients)• 0.75 mg/kg IV bolus then 1.75 mg/kg/h infusion with or without

prior treatment with UFH (dose adjustment to 1mg/kg/h with CrCl <30 mL/min) (IB)

Fondaparinux: not recommended as sole agent for PPCI (IIIB: Harm)


ACT: activated clotting time

Anticoagulation

FIBRINOLYTIC THERAPY


GP IIB/IIIA RECEPTOR ANTAGONIST

CLINICAL USE• Block the final common pathway of platelet aggregation (inhibiting cross-

linking of platelets through fibrinogen bridges)

• Rationale to use in combination with UFH:– Reduce likelihood of reinfarction – Prevent distal embolization of thrombi during PPCI

• Should not be administered for medical management of the patients with STEMI not undergoing PCI

• Administration of GP IIb/IIIa inhibitors should be avoided, if possible, with bivalirudin due to increased bleeding risk Beygui F et al. Eur Heart J Supp; 2005; 7: 110-114


CHOICE OF AGENTS

Agent Molecule Dose Contraindications

Abciximab(ReoPro®)

Monoclonal antibody

Bolus: 0.25 mg/kgInfusion: 0.125 mg/kg/hr x 12 hrs

Active bleeding, thrombocytopenia, prior stroke, renal dialysis (eptifibatide)

EptifibatideIntegrilin®)

Peptide Bolus: 180 mcg/kg x 2Infusion: 2 mcg/kg/min x 18-24 hrs(1 mcg/kg/min if CrCL <50)

Tirofiban(Aggrastat®)

Non-peptide

Bolus: 25 mcg/kg Infusion: 0.15 mcg/kg/min x 18 hrs

Beygui F et al. Eur Heart J Supp; 2005; 7: 110-114

POST PCI MANAGEMENT

ROUTINE MEDICAL THERAPIES

Therapy Indications Contraindications (CI) ACC/AHA Recommendations

B-blockers

Initiated in the first 24 hours in all patient s without CI

CHF, shock, reactive airway disease, PR interval >0.24 secs, 2nd or 3rd degree AV block, HR <60 bpm, SBP <90 mmHg

IB

ACEI

Initiated in the first 24 hours for patients with anterior infarction, LV dysfunction (EF ≤ 0.40) or HF

SBP <100 mmHg, intolerant to ACEI, bilateral renal stenosis, serum potassium >5.5 mmol/L, ARF, Pregnancy

IA

ARBFor patient intolerant to ACE

Same as ACEIIB

O’Gara PT et al. Circulation; 2013; 127DiPiro J. Acute Coronary Syndrome. In: Pharmacotherapy: A Pathophysiological Approach, 2011

ROUTINE MEDICAL THERAPIES

Therapy Indications Contraindications

(CI)ACC/AHA

Recommendations

Aldosterone Antagonists

LVEF ≤ 0.40 and either DM or HF who are already on ACEI and b-blockers

Hypotension, hyperkalemia (serum potassium >5.0 mmol/L), SCr >2.5 mmol/L or CrCl <30 mL/min

IB

Statin High intensity statin to all patients without CI

Serum transaminase 3X ULN, Pregnancy, active liver disease

IB

Nitroglycerin

Patient with ongoing ischemic discomfort, hypertension and HF

Hypotension , use of sildenafil/vardenafil within 24 h or tadalafil within 48 h

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O’Gara PT et al. Circulation; 2013; 127DiPiro J. Acute Coronary Syndrome. In: Pharmacotherapy: A Pathophysiological Approach, 2011

PATIENT CASE

CASE 1

SUBJECTIVE • C/C: “chest pain”

• HPI: – RS is a 59 yrs old Philippino male with no prior cardiac history presented at the

emergency room at 22:04 after having retrosternal chest pain for ~1.5 hours – Described chest pain as compressive in nature, radiating to both arms and associated

with sweating– Denied any history of shortness of breath, nausea, and vomiting

• PMHx:

– Hypertension (x 3 years) on amlodipine 10 mg by mouth daily, and aspirin 81 mg by mouth daily

• SHx: KFSH employee; current smoker

• FHx: unknown

• Allergy: NKA

• On Admission: – Vitals : BP: 123/70 mmHg; HR: 76 bpm; RR: 25 br/min; Temp: 36.6 0C;

O2 Sat: 98% 3L nasal cannula– Physical Exams: unremarkable • CVS: S1 + S2 + 0• Chest: clear; equal air entry with normal breath sounds• Ext: no significant changes, no JVD • CNS: no abnormality detected• Abd: not distended• Height: 148 cm; Weight: 87 kg (standing)

– ECG: ST segment abnormalities in V2-V6, and anterior leads– Chest X-Ray: mild increase in the interstitial marking but no definite

pneumonic infiltration or pleural effusion

OBJECTIVE

ECG(DAY OF ADMISSION)

LABS (DAY OF ADMISSION)

• Chemistry:

• CBC with differential: unremarkable

• Enzymes:

Na: 136 Cl: 103 Urea: 4.9 Glucose: 8.60 Ca (t): 2.22

K: 4.2 CO2: 22 Cr: 104 Mg: 0.91 PO4: 1.09

CK: 294 TrT: <0.01 Pro-BNP: 25 ALT: 22 AST: 21.4 Alk phos: 59

ASSESSMENT/PLAN • He was diagnosed with anteroseptal STEMI and was sent to the cath lab for PPCI

• Medication: – Heparin 7000 units (80 units/kg) IV push once

• Plan:– Immediate PCI – Admit to CCU after PCI for routine medical care

• Catheterization (23:56): PCI– LM: Normal– LAD: mid 99% followed by diffuse 20% lesion– LCx: Large dominant mild irregularities, OM-2 has Ostial 20% stenosis– RCA: small non dominant proximal 20% stenosis – Impression: single vessel coronary artery disease (LAD)– PCI to Mid LAD:• Resolute integrity (DES) deployed • Post intervention angio showed excellent result with TIMI 3 flow

Mid LAD Occlusion

LAD Occluded 99%

Stent Deployment

Resolute Integrity

Reperfusion following

stent

TIMI 3 Flow

POST PCI– DAY 1 • Vitals: unremarkable except tachypnea (RR:21-23 br/min)

• Labs:

• ECHO:• LV is normal in size. Apex, anterior septum, and anterior wall are akinetic

with partial loss of wall thickness. LV systolic function moderately reduced; EF 40-45%

• A/P: • Started on Metoprolol 25 mg PO twice a day, Atorvastatin 40 mg PO daily,

and Isosorbide dinitrate 20 mg twice a day• Continued aspirin and clopidogrel

CK: 2343 TrT: 6.930 ALT: 45.6 AST: 242.6


K: 4.5 CO2: 25 Cr: 99 Mg: 0.88 PO4: 1.09

Trig: 2.247 Chol: 4.757 HDL: 0.91 LDL: 3.0 HbA1c: 0.061

ECG(05:58)

• Vitals:

• Labs:

• Plan: • Patient is walking and doing well; plan to transfer to A4• Discharge medications:

1. Aspirin 81 mg PO daily2. Clopidogrel 75 mg PO daily 3. Metoprolol 25 mg PO twice a day 4. Isosorbide dinitrate 20 mg PO twice a day 5. Atorvastatin 40 mg PO daily

POST PCI– DAY 2


K: 4.4 CO2: 24 Cr: 104 Mg: 0.84 PO4: 0.98

CK: 902 TrT: 2.780

BP:120’s/70’s HR: 50’s-60’s RR: 15-18 Temp: 36.8 O2 Sat: 95% RA

SUMMARY • ST segment elevation MI/STEMI is a medical emergency which is the result of

complete occlusion of the coronary artery causing myocardial infarction

• Since atherosclerotic disease is the most common cause of STEMI, the pathophysiology is mainly due to the rupture of “vulnerable plaque”

• Clinical presentation of STEMI may differ by gender and age. However, in general patient presents with midline anterior and/or retrosternal pain

• Diagnosis of STEMI is based on:– Clinical symptoms, ECG changes, and release of cardiac biomarkers

• Goals of management is to restore blood flow to the infarct artery as promptly as possible to minimize infarct size

• Recommended time frame for PPCI in a skilled PCI capable facilities is ≤ 90 minutes otherwise fibrinolysis is preferred

• DAPT is indicated irrespective of modes of reperfusion therapy

• For PCI, anticoagulation therapy is provided once before procedure, whereas, the duration of therapy is longer in patients treated with fibrinolysis – UFH: 48 h, then other modes of anticoagulation – Enoxaparin: 8 days or until discharge

SUMMARY (CONT)

ST-Elevation Myocardial Infarction

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