Tauhid Ahmed Bhuiyan, PharmD PGY-1 Resident King 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)
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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
• 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
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
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
• 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
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