About Me

Bryce R. Burkhart, PharmD

PGY1 Pharmacy Resident IU Health Arnett Hospital
bburkhart@iuhealth.org
Review Questions – Diagnosis

 DK a 57 year old male presents to the ED with complaints of severe, crushing

chest pain that radiates to his back. Over the past couple days, he has
experienced increasing SOB. Troponin in the ED was 2.7 ng/mL. The ED ECG is
picture to the right. What is the most likely explanation for DK’s chest pain?
 A. Signs/Symptoms are consistent with stable angina
 B. Signs/Symptoms are consistent with unstable angina
 C. Signs/Symptoms are consistent with NSTEMI
 D. Signs/Symptoms are consistent with STEMI
Review Questions – Diagnosis

 DK a 57 year old male presents to the ED with complaints of severe, crushing

chest pain that radiates to his back. Over the past couple days, he has
experienced increasing SOB. Troponin in the ED was 2.7 ng/mL. The ED ECG is
picture to the right. What is the most likely explanation for DK’s chest pain?
 A. Signs/Symptoms are consistent with stable angina
 B. Signs/Symptoms are consistent with unstable angina
 C. Signs/Symptoms are consistent with NSTEMI
 D. Signs/Symptoms are consistent with STEMI
Review Questions – Initial Management

 DK a 57 year old male presents to the ED with complaints of severe, crushing chest
pain that radiates to his back. Over the past couple days, he has experienced
increasing SOB.
 PMH: HTN, GERD
 Home Medications: Lisinopril 20mg QD, Omeprazole 40mg QD, ASA 81mg QD, Tadalafil 5mg
PRN (DK reports taking his lisinopril, omeprazole, and ASA this morning. His last dose of
tadalafil was yesterday afternoon).
 Labs: O2 sat 87%, Troponin 2.7 ng/mL, ECG
 What agent should NOT be administered to DK as part of his early hospital care?
 A. ASA 244mg x1 dose
 B. Supplemental Oxygen
 C. Nitroglycerin 0.4mg Q5min x3 doses
 D. Morphine 4mg IV, followed by 2mg IV Q5-15min
Review Questions – Initial Management

 DK a 57 year old male presents to the ED with complaints of severe, crushing chest
pain that radiates to his back. Over the past couple days, he has experienced
increasing SOB.
 PMH: HTN, GERD
 Home Medications: Lisinopril 20mg QD, Omeprazole 40mg QD, ASA 81mg QD, Tadalafil 5mg
PRN (DK reports taking his lisinopril, omeprazole, and ASA this morning. His last dose of
tadalafil was yesterday afternoon).
 Labs: O2 sat 87%, Troponin 2.7 ng/mL, ECG
 What agent should NOT be administered to DK as part of his early hospital care?
 A. ASA 244mg x1 dose
 B. Supplemental Oxygen
 C. Nitroglycerin 0.4mg Q5min x3 doses
 D. Morphine 4mg IV, followed by 2mg IV Q5-15min
Review Questions - Antiplatelets

 DK is being prepared for PCI intervention for his ACS. No fibrinolytic therapy
has been administered. In addition to the therapies already administered,
which antiplatelet is the most appropriate for DK at this time?
 A. Effient 60mg x1 dose
 B. Plavix 300mg x1 dose
 C. Brilinta 180mg x1 dose
 D. Integrilin 180mcg/kg IV x2 doses
Review Questions - Antiplatelets

 DK is being prepared for PCI intervention for his ACS. No fibrinolytic therapy
has been administered. In addition to the therapies already administered,
which antiplatelet is the most appropriate for DK at this time?
 A. Effient 60mg x1 dose
 B. Plavix 300mg x1 dose
 C. Brilinta 180mg x1 dose
 D. Integrilin 180mcg/kg IV x2 doses
ACS Up To Now…
ACS
MONA

UA/NSTEMI STEMI

Ischemia Early Primary PCI Primary Fibrinolytics

Guided Strategy Invasive Strategy

Antiplatelets

Anticoagulation
Anticoagulation
Objectives

 Identify the pharmacologic classes and agents within each class used to treat ACS
 Describe the benefits of each class of medications used to treat ACS
 Discuss the indications, doses, precautions/contraindications, and monitoring of pharmacologic
agents used to treat ACS
 Develop a therapeutic care plan for a patient with UA, NSTEMI or STEMI and explain the rationale
for each medication you would or would not recommend
Recommended Readings

 Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC Guideline for the
Management of Patients with Non-ST-Elevation Acute Coronary Syndromes.
JACC. 2014;64(24):e139-e228.
 Collet JP, Thiele H, Barbato E, et al. 2020 ESC Guidelines for the management
of acute coronary syndromes in patients presenting without persistent ST-
segment elevation. Eur Heart J. 2020;0: 1-79.
 O’Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA Guideline for the
Management of ST-Elevation Myocardial Infarction. Circulation.
2013;127(4):e362-e425.
 Ibanez B, James S, Agewell S, et al. 2017 ESC Guidelines for the management
of acute myocardial infarction in patients presenting with ST-segment
elevation. Eur Heart J. 2018;39(2):119-177.
Parenteral
Anticoagulation
An anticoagulant should be administered to ________
ALL patients with ACS in addition to
antiplatelet therapy to reduce risk of intracoronary and catheter thrombus formation
irrespective of initial treatment strategy

Class I Guideline Recommended Agents

NSTEMI – Ischemia-Guided Strategy UFH, enoxaparin, fondaparinux
NSTEMI – Early Invasive Strategy UFH, enoxaparin, fondaparinux, bivalirudin
STEMI – Primary PCI UFH, bivalirudin
STEMI – Primary Fibrinolytics UFH, enoxaparin, fondaparinux
Coagulation Cascade
UFH

Enoxaparin

Fondaparinux

Antithrombin

Bivalirudin
 MOA: increases antithrombin activity
 Dosing:
 NSTEMI/STEMI + Primary Fibrinolytics: 60 unit/kg IV
bolus, followed by 12 unit/kg/hour continuous infusion
Max Bolus Dose: 4000 units
Unfractionated


 Max Infusion Rate: 1000 units/hour

 The rate of infusion is titrated based on hospital specific
aPTT Monitoring
protocol based on __________________
Heparin (UFH)
 NSTEMI/STEMI + PCI: 50-100 unit/kg loading dose
 Loading doses administered to target an activated clotting
time (ACT) of 200-300 seconds
 No maintenance infusions required for PCI
Unfractionated Heparin Dosing Nomogram

Do NOT Memorize
Heparin Nomogram Practice

 ES is a 72 year old male who is being started on a heparin drip for NSTEMI
based on an ischemia-guided strategy. Patient weighs 75kg. What is the
recommended bolus dose and starting infusion rate for ES’s heparin drip?
 Bolus Dose:
 Maintenance Infusion:
 The most recent aPTT level drawn is 103 seconds. Assuming the heparin drip
is now running at 940 units/hour, what is the most appropriate adjustment to
the heparin drip to make at this time? Please use the heparin nomogram on
the previous slide.
Heparin Nomogram Practice

 ES is a 72 year old male who is being started on a heparin drip for NSTEMI
based on an ischemia-guided strategy. Patient weighs 75kg. What is the
recommended bolus dose and starting infusion rate for ES’s heparin drip?
 Bolus Dose: 60 units/kg x 75 kg = 4,500 units  4,000 units (Max Bolus Dose)
 Maintenance Infusion: 12 units/kg/hour x 75 kg = 900 units/hour
 The most recent aPTT level drawn is 103 seconds. Assuming the heparin drip
is now running at 940 units/hour, what is the most appropriate adjustment to
the heparin drip to make at this time? Please use the heparin nomogram on
the previous slide.
 Decrease the heparin infusion rate to 790 units/hour, and repeat aPTT level in 6
hours
Unfractionated Heparin Dosing Nomogram
Unfractionated Heparin (UFH)

 Duration: 48 hours or until PCI is performed

 Contraindications: History of HIT, Severe Bleeding Risk
 Heparin Induced Thrombocytopenia (HIT): immune-mediated reduction in
__________;
platelets occurs within 4-10 days of heparin initiation
 Life-threatening; causes thrombocytopenia and increases risk of thrombosis
 Testing for Suspected HIT:
 Enzyme-linked immunosorbent assay (ELISA)- quick, high false positive rate
 Serotonin release assay (SRA)- gold standard for diagnosis, often a “send-out” lab
Questions

 True or False: If a patient is suspected of developing HIT, the heparin should

be discontinued, and the patient started on enoxaparin.
 True or False: Once a patient has been diagnosed with HIT, they should never
be re-challenged with UFH or LMWH.
 Which of the following agents may be considered for anticoagulation in a
patient where there is concern for HIT? (Select All That Apply)
 A: Argatroban
 B: Enoxaparin
 C: Bivalirudin
 D: Fondaparinux
Questions

 True or False: If a patient is suspected of developing HIT, the heparin should be

discontinued, and the patient started on enoxaparin.
 False: Though the LMWH are associated with a lower risk of HIT compared to heparin, they should
still not be used due to the potential risk
 True or False: Once a patient has been diagnosed with HIT, they should never be re-
challenged with UFH or LMWH.
 True: A UFH/LMWH re-challenge should not occur in any patient with a history of HIT
 Which of the following agents may be considered for anticoagulation in a patient where
there is concern for HIT? (Select All That Apply)
 A: Argatroban
 B: Enoxaparin
 C: Bivalirudin
 D: Fondaparinux
 Low Molecular Weight Heparin (LMWH)
 MOA: Similar to UFH; Anti-Xa > Anti-IIa
 Dosing:
 NSTEMI: 1 mg/kg SC every 12 hours
 An additional 0.3 mg/kg IV dose should be administered
to patients going for PCI if the last dose of enoxaparin


was > 8 hours ago
STEMI + Primary Fibrinolytics:
Enoxaparin
 Age < 75 years: 30 mg IV bolus, followed by 1 mg/kg SC
every 12 hours
(Lovenox)
 The first SC dose should be administered 15
minutes after the 30 mg IV bolus
 Age > 75 years: no bolus; 0.75 mg/kg SC every 12 hours
 Renal Dose Adjustment (CrCl <30 mL/min): 1 mg/kg SC
every 24 hours
Enoxaparin (Lovenox)

 Duration of Treatment: Up to 8 days OR until revascularization (PCI)

 Monitoring: Anti-Xa levels are not routinely performed; however, levels may
be beneficial in specific patient populations
 Extremes of Body Weight
 Renal Impairment
 Pregnancy
 Developing/Worsening Clot
Question

 LN is a 64 year old female with a STEMI and planning to undergo reperfusion

therapy with a fibrinolytic. Temp 37.1, BP 128/68, HR 87 bpm, RR 15, O2 sat
94% on room air. SCr 1.26 mg/dL. Patient weighs 48 kg. What is the most
appropriate dose of enoxaparin for this patient?
 A. 30mg bolus, followed in 15 minutes by 50mg Q12H
 B. 50mg Q12H
 C. 40mg Q12H
 D. 30mg bolus, followed in 15 minutes by 50mg Q24H
Question

 LN is a 64 year old female with a STEMI and planning to undergo reperfusion

therapy with a fibrinolytic. Temp 37.1, BP 128/68, HR 87 bpm, RR 15, O2 sat
94% on room air. SCr 1.26 mg/dL. Patient weighs 48 kg. What is the most
appropriate dose of enoxaparin for this patient? CrCl 34 mL/min
 A. 30mg bolus, followed in 15 minutes by 50mg Q12H
 B. 50mg Q12H
Age < 75 years: 30mg bolus,
followed in 15 minutes by 1 mg/kg Q12H
 C. 40mg Q12H
 D. 30mg bolus, followed in 15 minutes by 50mg Q24H
 MOA: Factor Xa Inibitor
 Dosing: Not preferred if planning PCI due to risk of
thrombosis
 NSTEMI: 2.5mg SC daily
 Administer UFH or bivalirudin if patient is on fondaparinux and


requires PCI
STEMI + Primary Fibrinolytics: 2.5mg IV bolus, followed by
Fondaparinux
2.5mg SC daily
 The first SC dose should be administered 24 hours after the IV
(Arixtra)
bolus
 Duration: Up to 8 days OR until revascularization (PCI)
 Contraindications: severe bleeding risk, CrCl < 30mL/min
 MOA: Direct thrombin inhibitor
 Dosing: Preferred in patients at high risk of bleeding
compared with UFH + GP IIb/IIIa receptor antagonist
 NSTEMI + PCI: 0.1 mg/kg IV bolus, followed by 0.25
mg/kg/hour IV infusion
 STEMI + PCI: 0.75 mg/kg IV bolus, followed by 1.75
mg/kg/hour IV infusion Bivalirudin
 Duration: discontinue at the end of PCI, but may be
continued for 4 hours post-PCI if needed (Angiomax)
 May be used in combination with GP IIb/IIIa receptor
antagonists as “bail out” therapy.
 Requires Renal Dosing Adjustments: Infusion Only
 CrCl <30 mL/min: 1 mg/kg/hour
 Dialysis: 0.25 mg/kg/hour
UFH vs. Bivalirudin: Which is Better?

 There are conflicting results when comparing bivalirudin vs. UFH

 Many studies compare bivalirudin to UFH; however, the UFH is often in combination with
a GP IIb/IIIa receptor antagonist.
 HEAT-PPCI Trial
 UFH may be more effective at preventing major adverse cardiovascular events (MACE)
compared to bivalirudin
 Bivalirudin may increase the risk of reinfarction and stent thrombosis
 BRIGHT & Matrix Trials
 Bivalirudin may be associated with a lower risk of bleeding compared with UFH
Questions

 Which of the heparinoid agents has the lowest affinity for factor IIa?
 A. Enoxaparin
 B. Fondaparinux
 C. UFH
 D. Bivalirudin
 Which anticoagulant, commonly utilized in the setting of PCI, may be used in
combination with abciximab for bail out therapy?
 A. Angiomax
 B. ReoPro
 C. Arixtra
 D. Lovenox
Questions

 Which of the heparinoid agents has the lowest affinity for factor IIa?
 A. Enoxaparin
 B. Fondaparinux
 C. UFH
 D. Bivalirudin
 Which anticoagulant, commonly utilized in the setting of PCI, may be used in
combination with abciximab for bail out therapy?
 A. Angiomax
 B. ReoPro
 C. Arixtra
 D. Lovenox
Anticoagulant Dosing

Agent NSTEMI Dosing STEMI Dosing Renal Dosing

Ischemia-Guided Early Invasive (PCI) Fibrinolytic PCI CrCl <30 mL/min

UFH LD: 60 units/kg IV LD: 50-100 units/kg IV LD: 60 units/kg IV LD: 50-100 units/kg IV Not Renally Dose
MD: 12 units/kg/hour IV MD: NONE MD: 12 units/kg/hour IV MD: NONE Adjusted
Enoxaparin LD: NONE LD: NONE LD*: 30 mg IV NOT USED MD: 1 mg/kg SC
MD: 1 mg/kg SC Q12H MD: 1 mg/kg SC Q12H MD*: 1 mg/kg SC Q12H Q24H
Fondaparinux LD: NONE Not Preferred: Requires LD: 2.5 mg IV NOT USED Contraindicated
MD: 2.5 mg SC Q24H UFH or bivalirudin MD: 2.5 mg SC Q24H
Bivalirudin NOT USED LD: 0.1 mg/kg IV NOT USED LD: 0.75 mg/kg IV MD**:
MD: 0.25 mg/kg/hour IV MD: 1.75 mg/kg/hour IV 1 mg/kg/hour IV

*In patients >75 years old, no LD is administered, and the MD is reduced to 0.75 mg/kg SC Q12H
**In dialysis patients the maintenance infusion rate is 0.25 mg/kg/hour
Anticoagulants For How Long?

UFH Enoxaparin Fondaparinux Bivalirudin

48 hours OR until < 8 days OR until < 8 days OR until At the end of PCI
PCI performed PCI performed PCI performed OR 4 hours post-PCI
Question

 PM is an 82 year old male who presented with NSTEMI and the cardiologist has
opted for early invasive therapy. Temp 37.6, BP is 132/73, HR 65bpm, RR 18,
O2 sat 98% on room air. SCr = 0.62 mg/dL. Patient weighs 62kg. Patient
received ASA 325mg x 1, clopidogrel 600mg x 1. What is the best
recommendation regarding his anticoagulation?
 A. UFH 60 units/kg IV, followed by 12 units/kg/hour titrated to aPTT
 B. Enoxaparin 60mg SC Q12H
 C. Bivalirudin 0.75 mg/kg IV, followed by 1.75 mg/kg/hour
 D. Fondaparinux 2.5mg SC Q24H
Question

 PM is an 82 year old male who presented with NSTEMI and the cardiologist has
opted for early invasive therapy. Temp 37.6, BP is 132/73, HR 65bpm, RR 18,
O2 sat 98% on room air. SCr = 0.62 mg/dL. Patient weighs 62kg. Patient
received ASA 325mg x 1, clopidogrel 600mg x 1. What is the best
recommendation regarding his anticoagulation? CrCl 80 mL/min
 A. UFH 60 units/kg IV, followed by 12 units/kg/hour titrated to aPTT
 B. Enoxaparin 60mg SC Q12H
 C. Bivalirudin 0.75 mg/kg IV, followed by 1.75 mg/kg/hour
 D. Fondaparinux 2.5mg SC Q24H
Question

 PM is an 82 year old male who presented with NSTEMI and the cardiologist has
opted for early invasive therapy. Temp 37.6, BP is 132/73, HR 65bpm, RR 18,
O2 sat 98% on room air. SCr = 0.62 mg/dL. Patient weighs 62kg. Patient
received ASA 325mg x 1, clopidogrel 600mg x 1. Based on your answer in the
previous question, what is the most appropriate anticoagulation duration of
therapy?
 A. 24 hours
 B. 48 hours
 C. Until PCI
 D. Until hospital discharge (up to 8 days)
Question

 PM is an 82 year old male who presented with NSTEMI and the cardiologist has
opted for early invasive therapy. Temp 37.6, BP is 132/73, HR 65bpm, RR 18,
O2 sat 98% on room air. SCr = 0.62 mg/dL. Patient weighs 62kg. Patient
received ASA 325mg x 1, clopidogrel 600mg x 1. Based on your answer in the
previous question, what is the most appropriate anticoagulation duration of
therapy?
 A. 24 hours
 B. 48 hours
 C. Until PCI
 D. Until hospital discharge (up to 8 days)
Question

 Which anticoagulant is an option for each type of ACS management strategy?

 A. UFH
 B. Enoxaparin
 C. Fondaparinux
 D. Bivalirudin
 Which ACS management strategy may utilize any of the parenteral
anticoagulants?
 A. NSTEMI – Ischemia Guided Strategy
 B. STEMI – Primary PCI
 C. NSTEMI – Early Invasive Strategy
 D. STEMI – Primary Fibrinolytics
Question

 Which anticoagulant is an option for each type of ACS management strategy?

 A. UFH
 B. Enoxaparin
 C. Fondaparinux
 D. Bivalirudin
 Which ACS management strategy may utilize any of the parenteral
anticoagulants?
 A. NSTEMI – Ischemia Guided Strategy
 B. STEMI – Primary PCI
 C. NSTEMI – Early Invasive Strategy
 D. STEMI – Primary Fibrinolytics
Review

An anticoagulant should be administered to ALL patients with ACS in addition to

antiplatelet therapy to reduce risk of intracoronary and catheter thrombus formation
irrespective of initial treatment strategy

Class I Guideline Recommended Agents

NSTEMI – Ischemia-Guided Strategy
NSTEMI – Early Invasive Strategy
STEMI – Primary PCI
STEMI – Primary Fibrinolytics
Review

An anticoagulant should be administered to ALL patients with ACS in addition to

antiplatelet therapy to reduce risk of intracoronary and catheter thrombus formation
irrespective of initial treatment strategy

Class I Guideline Recommended Agents

NSTEMI – Ischemia-Guided Strategy
UFH enoxaparin fondaparinux
NSTEMI – Early Invasive Strategy
STEMI – Primary PCI UFH enoxaparin fondaparinux bivalirudin
STEMI – Primary Fibrinolytics UFH bivalirudin
UFH enoxaparin fondaparinux
 Questions?
Contact Information: bburkhart@iuhealth.org