ST-Elevation Myocardial Infarction
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Transcript of 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)
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
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/
O’Gara PT et al. Circulation; 2013; 127
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
O’Gara PT et al. Circulation; 2013; 127
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
DiPiro J. Acute Coronary Syndrome. In: Pharmacotherapy: A Pathophysiological Approach, 2011
ACC/AHA CLASSIFICATION OF RECOMMENDATIONS
O’Gara PT et al. Circulation; 2013; 127
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)
DiPiro J. Acute Coronary Syndrome. In: Pharmacotherapy: A Pathophysiological Approach, 2011
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)
O’Gara PT et al. Circulation; 2013; 127
O’Gara PT et al. Circulation; 2013; 127
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
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
O’Gara PT et al. Circulation; 2013; 127
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
Hilleman DE et al. Pharmacotherapy. 2007;27(11):1558-1570
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
Hilleman DE et al. Pharmacotherapy. 2007;27(11):1558-1570
*KFSH&RC formulary
CONTRAINDICATIONS TO FIBRINOLYTIC THERAPY
O’Gara PT et al. Circulation; 2013; 127
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)
O’Gara PT et al. Circulation; 2013; 127
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
O’Gara PT et al. Circulation; 2013; 127
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
++++ +++ �
Alexopoulos D. Int J Card; 2013; 163:249-55
MAJOR TRIALS—OUTCOME COMPARISON
Alexopoulos D. Int J Card; 2013; 163:249-55
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)
O’Gara PT et al. Circulation; 2013; 127
ACT: activated clotting time
Anticoagulation
FIBRINOLYTIC THERAPY
O’Gara PT et al. Circulation; 2013; 127
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
DiPiro J. Acute Coronary Syndrome. In: Pharmacotherapy: A Pathophysiological Approach, 2011
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
�
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
Na: 137 Cl: 101 Urea: 3.9 Glucose: 5.89 Ca (t): 2.040
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
Na: 137 Cl: 102 Urea: 5.9 Glucose: 5.96 Ca (t): 2.090
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)