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Treatment Guidelines for ST-segment

Elevation Myocardial Infarction


(STEMI) and Non ST-segment Elevation
Myocardial Infarction (NSTEMI)
Brady Helmink
University of Nebraska Medical Center
College of Pharmacy
Class of 2013 Pharm.D. candidate

Objectives

Understand which conditions classify as Acute


Coronary Syndromes (ACS)
Identify the difference between the presentation of
NSTEMI vs. STEMI
Know how to stratify patients with NSTEMI using the
TIMI risk score
Compare and contrast treatment algorithms for high
and low-risk patients with NSTEMI

Objectives

Explain how the pathophysiology of STEMI differs


from NSTEMI
Understand the importance of PCI and time to
revascularization in both NSTEMI and STEMI
Recognize the significance of fibrinolytic agents and
their place in therapy
Discuss similarities and differences between the
treatment of STEMI and NSTEMI

Acute Coronary Syndrome (ACS)

Refers to anginal symptoms at rest for > 20 minutes;


may or may not be relieved by SL NTG
Three categories
ST-segment Elevation Myocardial Infarction (STEMI)
Non ST-segment Elevation Myocardial Infarction (NSTEMI)
Unstable Angina (UA)

Management focused on rapid diagnosis, risk


stratification, and therapies to restore coronary blood
flow and reduce myocardial ischemia
DiPiro, Joseph T. "Chapter 24. Acute Coronary Syndromes." Pharmacotherapy: A Pathophysiologic Approach. New
York, N.Y: McGraw-Hill Medical, 2011. Access Pharmacy.
http://www.accesspharmacy.com/content.aspx?aID=7972196

Patient Case

BC, a 61 year-old female presents to the Onawa


ER with progressive substernal chest pain radiating
up into her neck and jaw over the past four days
Initial EKG showed non-specific T wave changes and
cardiac troponin levels were elevated at 1.3
Coronary arteriography showed 90% stenosis of
the LAD

Patient Case (cont.)

Past medical history of DM 2, HTN, HLD, depression


and recurrent bronchitis. Patient is a long-standing
and ongoing tobacco user, and also has a positive
family history of CAD
Home medications include ASA 81mg daily,
metoprolol XL 25mg daily, HCTZ 12.5mg daily,
lisinopril 20mg daily, cymbalta 60mg daily, apidra
on sliding scale, and lantus 25 units QHS

NSTEMI

Defined as angina at rest for > 20 min without STsegment elevation, but with a rise in cardiac
markers
Pathophysiology
in myocardial oxygen supply
Thrombus formation on an atherosclerotic plaque
Abrupt

Management depends on risk stratification


TIMI

(Thrombolysis in Myocardial Infarction) risk score

DiPiro, Joseph T. "Chapter 24. Acute Coronary Syndromes." Pharmacotherapy: A Pathophysiologic Approach. New
York, N.Y: McGraw-Hill Medical, 2011. Access Pharmacy.
http://www.accesspharmacy.com/content.aspx?aID=7972196

Risk Stratification for NSTEMI

One point is assigned for each of the following risk


factors
1.
2.

3.
4.

5.
6.
7.

Age 65 years
3 or more CHD risk factors: smoking, hypercholesterolemia,
hypertension, diabetes mellitus, family history of premature
CHD death/events
Known CAD (50% stenosis of at least one major coronary
artery on coronary angiogram)
Aspirin use within the past 7 days
2 or more episodes of chest discomfort within the past 24 hrs
ST-segment depression 0.5 mm
Positive biochemical marker for infarction

Antman, EM, et al. The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication and
therapeutic decision making. JAMA. 2000 Aug 16; 284(7):835-42

Patient Case

BC, a 61 year-old female presents to the Onawa


ER with progressive substernal chest pain radiating
up into her neck and jaw over the past four days
Multiple episodes of chest pain
Initial EKG showed non-specific T wave changes and
troponin levels were elevated at 1.3 Positive
cardiac markers
Coronary arteriography showed 90% stenosis of
the LAD Known CAD

Patient Case (cont.)

Past medical history of DM 2, HTN, HLD, depression


and recurrent bronchitis. Patient is a long-standing
and ongoing tobacco user, and also has a positive
family history of CAD 3 CHD risk
equivalents
Home medications include ASA 81mg daily,
metoprolol XL 25mg daily, HCTZ 12.5mg daily,
lisinopril 20mg daily, cymbalta 60mg daily, apidra
on sliding scale, and lantus 25 units QHS ASA
use in the past 7 days

TIMI risk score for NSTEMI


High-risk
TIMI risk score
57 points

TIMI risk score


0/1
2
3
4
5
6/7

Medium-risk
TIMI risk Score
34 points

Low-risk
TIMI risk score
02 points

Mortality, MI, or severe recurrent ischemic requiring urgent


target vessel revascularization
4.7%
8.3%
13.2%
19.9%
26.2%
40.9%

DiPiro, Joseph T. "Chapter 24. Acute Coronary Syndromes." Pharmacotherapy: A Pathophysiologic Approach. New
York, N.Y: McGraw-Hill Medical, 2011. Access Pharmacy.
http://www.accesspharmacy.com/content.aspx?aID=7972196

Invasive vs. Conservative strategy

Invasive (high-risk patients)


Antiplatelet

and Anticoagulation therapies followed by


revascularization
Percutaneous

Coronary Intervention (PCI) OR


Coronary Artery Bypass Grafting (CABG)

Conservative (low-risk patients)


Antiplatelet

and Anticoagulation therapies followed by


watchful waiting

Hoenig MR, Aroney CN, Scott IA. Early invasive versus conservative strategies for unstable angina and non-ST elevation
myocardial infarction in the stent era. Corchrane Database Syst review 2010; Mar 17; 3:CD004815.
Mahoney M, Jurkovitz CT, Chu H, et al. Cost and cost-effectiveness of an early invasive vs conservative strategy for the
treatment of unstable angina and non-ST-segment elevation myocardial infarction. JAMA 2002; 288: 1851
8185.
Kushner FG, Hand M, Smith SC Jr, et al. 2009 Focused Updates: ACC/AHA Guidelines for the Management of Patients
with ST-Elevation Myocardial Infarction and ACC/AHA/SCAI Guidelines on Percutaneous Coronary
Intervention. 2009; 120: 22712306.

Pharmacologic Management of
NSTEMI

Antiplatelet therapy

Aspirin 162-325mg chewed immediately and 81-162mg


continued indefinitely
Clopidogrel 600mg load for pts undergoing PCI and 75mg
daily continued for at least 12 months
+/- GP IIb/IIIa inhibitor (only for high risk patients who are
likely to undergo invasive strategy: elevated troponin or STsegment depression)
o

Eptifibatide (Integrilin) Two180mcg/kg boluses 10min apart,


followed by a 2mcg/kg/minute infusion for 72-96 hours

Quantitative comparison of clopidogrel 600 mg, prasugrel and ticagrelor, against clopidogrel 300 mg on major
adverse cardiovascular events and bleeding in coronary stenting: synthesis of CURRENT-OASIS-7, TRITONTIMI-38 and PLATO. Int J Cardiol. 2012 Jul 12; 158(2): 181-5. Epub 2012 Jan 10.
Giugliano, Robert P. et al. Early versus Delayed, Provisional Eptifibatide in Acute Coronary Syndromes. N Engl J Med
2009; 360: 2176-2190

Pharmacologic Management of
NSTEMI

Anticoagulation

Heparin 60-70 units/kg IV bolus, followed by 12-15


units/kg/hr continuous IV infusion
o

DC Heparin when going to PCI

OR

Enoxaparin 1mg/kg Q12hrs

OR

Bivalirudin with PCI, give 0.75mg/kg IV bolus,


followed by continuous IV infusion 1.75mg/kg/hr. DC at
end of procedure or continue for up to 4 hours

Enoxaparin vs Unfractionated Heparin in High-Risk Patients With NonST-Segment Elevation Acute Coronary
Syndromes Managed With an Intended Early Invasive Strategy. JAMA. 2004; 292(1): 45-54.
Stone GW, McLaurin BT, Cox DA, et al. Bivalirudin for patients with acute coronary syndromes. N Engl J Med 2006;
355: 2203-2216.

Pharmacologic Management of
NSTEMI

Beta blockers

Metoprolol IV 5mg given over 1-2 minutes Q5min X 3 doses;


convert to PO 25-50mg Q6hrs

Nitrates

SL NTG Q5min X 3 doses


IV NTG for pts with refractory angina
o

5-10mcg/min IV; by 10mcg/min Q5min to a max of 100mcg/min

Morphine Sulfate

2-5mg IV Q5-30min PRN pain

DiPiro, Joseph T. "Chapter 24. Acute Coronary Syndromes." Pharmacotherapy: A Pathophysiologic Approach. New
York, N.Y: McGraw-Hill Medical, 2011. Access Pharmacy.
http://www.accesspharmacy.com/content.aspx?aID=7972196

Pharmacologic Management of
NSTEMI

ACE inhibitors

HOPE trial
o
o

Attenuates the ventricular remodeling process


Early administration mortality in AMI patients

Statins

Helps with long-term atherosclerotic plaque stabilization


o

High doses most beneficial (treat to LDL < 70 mg/dL)

Effects of an Angiotensin-ConvertingEnzyme Inhibitor, Ramipril, on Cardiovascular Events in High-Risk Patients. N Engl


J Med 2000; 342: 145-153
Daga, Lal C., Upendra Kaul, and Aijaz Mansoor. "Approach to STEMI and NSTEMI." J Assoc Physicians India. 2011
Dec; 59 Suppl: 19-25

BC received

Patient Case

Heparin 6000 unit IV bolus (70 units/kg), followed by


1200 units/hr (14 units/kg/hr) continuous IV infusion*
ASA 162mg daily*
Clopidogrel 300mg load, followed by 75mg daily*
Lisinopril 10mg daily
Metoprolol XL 25mg BID
Morphine 2mg IV Q2hrs PRN
NTG SL 2 tablets relieved symptoms
NTG IV cont. 250mL bottle titrated to pain free*
Simvastatin 80mg initially, followed by 40mg daily

Patient Case

Procedure
PCI

w/ placement of drug eluting stent in LAD

Medications (given intra-arterial)


Heparin

3000 units
NTG 600mcg initially, 400mcg after 30min
Bivalirudin 65mg, or 13 mL IV bolus (0.75mg/kg),
followed by continuous IV infusion of 30mL/hr
(1.75mg/kg/hr). DCd at end of procedure

STEMI

Defined as prolonged chest discomfort unrelieved


by SL NTG with ST-segment elevation on EKG and a
rise in cardiac markers
Pathophysiology
Total

or near-total thrombotic occlusion of a coronary


artery

Management involves immediate reperfusion


therapy (PCI preferred)
Door-to-balloon

time is 90 minutes

DiPiro, Joseph T. "Chapter 24. Acute Coronary Syndromes." Pharmacotherapy: A Pathophysiologic Approach. New
York, N.Y: McGraw-Hill Medical, 2011. Access Pharmacy.
http://www.accesspharmacy.com/content.aspx?aID=7972196

Fibrinolytic therapy in STEMI

If > 90 minutes from nearest cardiac cath lab,


fibrinolytic therapy can risk of mortality
Door-to-needle time is 30 minutes
Fibrinolytics may be administered if patient presents
within 12 hrs of symptom onset
t-PA

(alteplase)
r-PA (retaplase)
TNK (tenecteplase)

Shown to open occluded artery in 60-90% of pts and


mortality by 20%
Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the
ASSENT-2 double-blind randomised trial. Lancet. 1999 Aug 28; 354(9180): 716-22.

Pharmacologic Management of
STEMI

Antiplatelet therapy
Aspirin 162-325mg chewed immediately and 81162mg continued indefinitely
Clopidogrel 300mg load for pts undergoing PCI or
receiving fibrinolytic and 75mg daily continued for at
least 14 days and up to12 months
Generally do not use GP IIb/IIIa inhibitors in the setting
of STEMI due to no improvement in outcomes and an
increased risk of bleeding

Pharmacologic Management of
NSTEMI

Anticoagulation
With

fibrinolytic

Heparin

60 units/kg IV bolus, followed by 12 units/kg


continuous IV infusion
OR

Enoxaparin

Without

30mg IV bolus, followed by 1mg/kg Q12hrs

fibrinolytic

Heparin

60-70 units/kg IV bolus, followed by 12-15


units/kg continuous IV infusion
OR

Enoxaparin

1mg/kg Q12hrs

Pharmacologic Management of
STEMI

Beta blockers

Nitrates

Morphine Sulfate

ACE inhibitors

Statins

Dosing similar to
NSTEMI

References
1.

2.

3.

4.

5.

6.

DiPiro, Joseph T. "Chapter 24. Acute Coronary Syndromes." Pharmacotherapy: A


Pathophysiologic Approach. New York, N.Y: McGraw-Hill Medical, 2011. Access Pharmacy.
http://www.accesspharmacy.com/content.aspx?aID=7972196
Antman, EM, et al. The TIMI risk score for unstable angina/non-ST elevation MI: A method
for prognostication and therapeutic decision making. JAMA. 2000 Aug 16; 284(7):835-42.
Hoenig MR, Aroney CN, Scott IA. Early invasive versus conservative strategies for unstable
angina and non-ST elevation myocardial infarction in the stent era. Corchrane Database Syst
review 2010;Mar 17;3:CD004815.
Mahoney M, Jurkovitz CT, Chu H, et al. Cost and cost-effectiveness of an early invasive vs
conservative strategy for the treatment of unstable angina and non-ST-segment elevation
myocardial infarction. JAMA 2002;288:18518185.
Kushner FG, Hand M, Smith SC Jr, et al. 2009 Focused Updates: ACC/AHA Guidelines for
the Management of Patients with ST-Elevation Myocardial Infarction and ACC/AHA/SCAI
Guidelines on Percutaneous Coronary Intervention. 2009;120:22712306.
Quantitative comparison of clopidogrel 600 mg, prasugrel and ticagrelor, against
clopidogrel 300 mg on major adverse cardiovascular events and bleeding in coronary
stenting: synthesis of CURRENT-OASIS-7, TRITON-TIMI-38 and PLATO. Int J Cardiol. 2012
Jul 12;158(2):181-5. Epub 2012 Jan 10.

References (cont.)
7.

8.

9.

10.

11.

12.

Giugliano, Robert P. et al. Early versus Delayed, Provisional Eptifibatide in Acute


Coronary Syndromes. N Engl J Med 2009; 360:2176-2190
Enoxaparin vs Unfractionated Heparin in High-Risk Patients With NonST-Segment
Elevation Acute Coronary Syndromes Managed With an Intended Early Invasive
Strategy. JAMA. 2004;292(1):45-54.
Stone GW, McLaurin BT, Cox DA, et al. Bivalirudin for patients with acute coronary
syndromes. N Engl J Med 2006; 355:2203-2216.
Effects of an Angiotensin-ConvertingEnzyme Inhibitor, Ramipril, on Cardiovascular
Events in High-Risk Patients. N Engl J Med 2000; 342:145-153
Daga, Lal C., Upendra Kaul, and Aijaz Mansoor. "Approach to STEMI and NSTEMI." J
Assoc Physicians India. 2011 Dec;59 Suppl:19-25.
Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial
infarction: the ASSENT-2 double-blind randomised trial. Lancet. 1999 Aug
28;354(9180):716-22.