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Acute Coronary Syndromes
Table of Contents
• Introduction
• Management of ACS
– Aims of therapy
• Short term and long term
– Overview of therapy
• Initial assessment
• Initial intervention
• Early pharmacotherapy of ACS
– Acute management of ACS
– Long term management
Acute coronary syndromes (ACSs):
• Is a term that includes all clinical syndromes compatible
with acute myocardial ischemia resulting from an
imbalance between myocardial oxygen demand and
supply.
• In contrast to stable angina, an ACS results primarily from
diminished myocardial blood flow secondary to an
occlusive coronary artery thrombus.
• ACSs are classified according to electrocardiographic
changes into:
1. ST Segment-Elevation MI (STEMI).
2. Non-ST-Segment-Elevation MI (NSTEMI).
3. Unstable Angina (UA).
ESC 2015
Pathophysiology
• A thrombus containing more platelets than fibrin, or
“white clot” generally produces an incomplete
occlusion of the coronary lumen and is more common
in non-ST-segment elevation ACS.
• The vessel generally is completely occluded by a “red
clot” that contains larger amounts of fibrin and red
blood cells but smaller amount of platelets.
• Infarct area may recover after 12 – 24 hrs of ischemia
because of collateral blood flow within the infarct area.
Comparison of ACSs
Unstable
Angina
NSTEMI
STEMI
+
+
+
ECG changes
None
ST segment
depression, T wave
inversion, or no
changes
ST segment
elevation
Biochemical
marker
No changes
Increased troponins &
CK MB
Increased troponins
& CK MB
Symptoms
present
Presentation of Acute Coronary Syndromes
General
• The patient typically is in acute distress and may develop or present with cardiogenic
shock.
Subjective criteria:
• classic symptoms
– Chest pain described as chest pressure or squeeze sensation in 70-80% of patients
(>20 min)
– Also the pain may be felt in epigastrium, arms, shoulders & may in jaw or back.
– Movement, deep breathing or change in body position doesn’t affect the pain.
• Other symptoms include:
– Diaphoresis.
– Nausea and vomiting.
– Shortness of breath.
– Arm tingling/ numbness.
– Weakness.
– Light headedness or syncope
• Patients less likely to present with classic symptoms include elderly patients, diabetic
patients, and women  May be silent in 15-20% of the patients
Biochemical Markers
• Evaluate troponin & CK MB to confirm MI
– released in response to myocardial necrosis
•
•
CK-MB (early diagnosis): If CK-MB  6% of total CK, MI occurred.
Cardiac Troponin I & T (most preferred & sensitive one), but can not
detect early MI & reinfarction. Onset 2-4 hrs, duration for Tropnin I is
7 days and Tropnin T is 10 –14 days.
• 3 measurements taken over the 1st 12 to 24 hrs
• MI diagnosis:
– > 1 one troponin value greater than MI decision limit set by lab
or
– 2 CK MB values greater than MI decision limit set by lab
Evolving MI is defined by the ACC as “typical rise and gradual fall (troponin) or
more rapid rise and fall (CK-MB) of biochemical markers of myocardial necrosis.”
Homework:
1. Criteria for MI based on cardiac enzymes
2. What is the preferred lab test for early reinfarction?
Source: Pharmacotherapy Principles & Practice
Treatment of ACS’s
Desired outcomes
Short-term desired outcomes in a patient with ACS are:
1. Early restoration of blood flow to the infarct-related artery to prevent
infarct expansion (in the case of MI) or prevent complete occlusion
and MI (in unstable angina)
2. Prevention of death and other complications
3. Prevention of coronary artery reocclusion
4. Relief of ischemic chest discomfort
5. Resolution of ST-segment and T-wave changes on ECG
Long-term desired outcomes are:
1. control of risk factors,
2. prevention of additional cardiovascular events,
3. improvement in quality of life.
General Approach
• Admission to
– ICU or CCU and may be an intermediate CU.
• Close monitoring of
– Vital sings, symptoms, & the ECG.
• Bed rests (1st 12 hrs).
• Restrict activity for the 1st 2-3 days.
• Diet
– small multiple meals,
– low Na and saturated fats and cholesterol.
• Stool softener
– Docusate Na 100 mg or
– Ca 240 mg once or twice daily.
Important
Refer to TABLE 24-4 (Dipiro)
Evidence-Based Pharmacotherapy for STsegment Elevation and Non-ST-segment
Elevation Acute Coronary Syndromes
Indications, dosing and contraindications of
different agents
STE-ACS
2013 ACCF/AHA STE-ACS
Acute Management STEMI
• Select reperfusion strategy
• Give antiplatelet therapy +ASA
• Give anticoagulant therapy to all
patients
Acute Management STEMI
• Select reperfusion strategy
• PCI vs fibrinolytics
– Enhanced survival
– lower rate of intracranial hemorrhage and recurrent MI
• 2013 ACCF/AHA
– PCI for any patient with an acute STEMI who can
undergo the procedure in a timely manner by persons
skilled in the procedure
– Timely is
• 90 minutes or less
– Patients transported to PCI-capable hospital or
• 120 minutes or less
– Patients who initially arrive at or are transported to a non-PCI capable hospital and
are then taken to a PCI-capable hospital.
Acute management STEMI
Select reperfusion strategy:
• Primary percutaneous coronary intervention (PCI) strongly
preferred, especially for patients with cardiogenic shock, heart
failure, late presentation, or contraindications to fibrinolysis.
Activate cardiac catheterization team as indicated. For patients
with symptoms of >12 hours, fibrinolytic therapy is not indicated,
but emergent PCI may be considered, particularly for patients with
evidence of ongoing ischemia or those at high risk.
• Treat with fibrinolysis if PCI unavailable within 90-120 minutes,
symptoms <12 hours, and no contraindications
Indications and contraindications to fibrinolytic therapy according to
ACC/AHA guidelines for management of patients with STE-MI
Acute Management STEMI
• Select reperfusion strategy
• 2013 ACCF/AHA
– The use of fibrinolytic therapy in patients with symptom
onset within 12 hours who cannot receive primary
percutaneous coronary intervention within 120 minutes of
first medical contact.
– The time interval from hospital arrival to initiation of
fibrinolytic drug infusion should be less than 30
minutes
2013 ACCF/AHA STEACS Circulation. 2013;127:529-555
Reperfusion – STEMI
• Either fibronylsis or primary Percutaneous Coronary Intervention (PCI) is the
treatment of choice for reestablishing coronary artery blood flow for patients
ST-segment-elevation ACS when the patient presents within 3 hours of
symptom onset.
• The ACC/AHA defines a target time to initiate reperfusion treatment for
STEMI:
– within 30 minutes of hospital presentation for fibrinolytics /and
– within no more than 90 minutes from presentation for primary PCI.
• The sooner the infarct-related coronary artery is opened in these patients, the
lower is their mortality and the greater is the amount of preserved
myocardium.
• For primary PCI, the patient is taken from the emergency department to the
cardiac catheterization laboratory and undergoes coronary angiography with
either balloon angioplasty or stent placement.
• While all patients should be evaluated for reperfusion therapy, not all patients
may be eligible.
Primary PCI is generally preferred in:
•
•
•
•
•
•
•
•
Patients presenting to institutions with skilled interventional cardiologists and a
catheterization laboratory immediately available
Patients with cardiogenic shock
Patients with contraindications to fibrinolytics
Patients presenting with symptom onset greater than 3 hours.
Patients in whom fibrinolysis was not successful
Patients presenting later in cardiogenic shock
Patients with life-threatening ventricular arrhythmias
Patients with persistent ischemia or signs of ischemia on stress testing following
MI.
• A meta-analysis comparing fibrinolysis with PCI indicated lower
mortality rate in PCI patients
• PCI opens arteries better than fibrinolytics
– reduces risk of major bleeding, intracranial hemorrhage (ICH)
– better side effect profile
Rapid overview: Management of acute coronary syndrome (ACS)
Rapid overview: Management of acute coronary syndrome (ACS)
Rapid overview: Management of acute coronary syndrome (ACS)
Rapid overview: Management of acute coronary syndrome (ACS)
Rapid overview: Management of acute coronary syndrome (ACS)
Rapid overview: Management of acute coronary syndrome (ACS)
Aspirin dose recommendations
• initial: 162 to 325 mg given on presentation (patient should
chew nonenteric-coated aspirin especially if not taking before
presentation) (ACC/AHA [Amsterdam 2014]; ACCF/AHA [O'Gara
2013]); for patients unable to take oral, may use a rectal
suppository dose of 600 mg (Maalouf 2009).
• Maintenance (secondary prevention): 81 to 325 mg once daily
continued indefinitely; when aspirin is used with ticagrelor, the
recommended maintenance dose of aspirin is 81 mg/day
(ACC/AHA [Amsterdam 2014]; ACCF/AHA [O’Gara 2013])
According to the STEMI guidelines, 81 mg once daily is preferred
(ACCF/AHA [O’Gara 2013]).
Aspirin dose recommendations
• After stenting ??
• The American College of Chest Physicians recommends the use
of 75 to 325 mg once daily (in combination with clopidogrel) for
1 month in patients receiving a bare metal stent or 3 to 6
months (dependent upon drug eluting stent type) followed by
75 to 100 mg once daily (in combination with clopidogrel) for up
to 12 months. For patients who underwent PCI but did not have
stent placement, 75 to 325 mg once daily (in combination with
clopidogrel) for 1 month is recommended. In either case, single
antiplatelet therapy (either aspirin or clopidogrel) is
recommended indefinitely (ACCP [Guyatt 2012]).
†Balloon angioplasty without stent placement may be used in selected patients. It might be
reasonable to provide P2Y12 inhibitor therapy to patients with STEMI undergoing balloon
angioplasty alone according to the recommendations listed for BMS. (LOE: C)
2013 ACCF/AHA STEACS Circulation. 2013;127:529-555
2013 ACCF/AHA STEACS Circulation. 2013;127:529-555
Thrombolytics C/I in acute STEMI
Absolute
Uptodate® 10/2013
Thrombolytics C/I in acute STEMI
Relative
Uptodate® 10/2013
Fibrinolytic agents complications
• Hemorrhagic complications:
– Stroke, < 2%.
– Intracranial hemorrhage, < 1% (Most serious occurred within
1st 24 hrs).
– It’s similar for all agents but > in female, blacks, > 75 years
old, low weight, Hx of CAD or HTN… etc.
• Major bleedings,
– 1.1 %, mainly when combined with coronary revascularization procedures.
– ICH rates higher in fibrin specific agents
– systemic bleeding other than ICH higher with streptokinase
• Allergic reactions
• More frequently with streptokinase and APSAC (anistreplase)
Differences in adjunct therapy
• Antiplatelets
–
–
–
–
Ticagrelor and prasugrel in PCI not lytics
Higher loading dose in PCI
Maintenance dose for longer duration
GPIIb/IIIa in PCI only
• Anticoagulants
–
–
–
–
UFH infusion in lytics not in PCI
Dosing according to ACT in PCI
Dosing according to aPTT in lytics
Enoxaparin in lytics not PCI
– Bivalirudin in PCI not lytics
– Fondaparinux in lytics not PCI
Routine Medical Therapies: STE-ACS
• Beta Blockers
• Class 1
– Oral initiated in the first 24 hours (LOE: B)
• Unless:
–
–
–
–
–
–
signs of HF,
evidence of a low-output state,
increased risk for cardiogenic shock,
PR interval more than 0.24 seconds,
second- or third-degree heart block,
active asthma, or reactive airways disease
– Continued during and after hospitalization (LEO: B)
2013 ACCF/AHA STEACS Circulation. 2013;127:529-555
Routine Medical Therapies
• Beta Blockers
• Class IIa
– It is reasonable to administer IV BB at the time of
presentation to pt who are hypertensive or have
ongoing ischemia.(LOE: B)
2013 ACCF/AHA STEACS Circulation. 2013;127:529-555
Routine Medical Therapies
• Renin-Angiotensin-Aldosterone System Inhibitors
• Class I
– ACEI administered in the first 24 hours: (LEO: A)
• anterior location MI,
• HF, or EF<40%
– ARB
• intolerant of ACEI (LOE: B)
– Aldosterone antagonist (LOE: B)
• receiving an ACEI + BB + EF < 40% + symptomatic HF or
• receiving an ACEI + BB + EF < 40% + DM
2013 ACCF/AHA STEACS Circulation. 2013;127:529-555
Routine Medical Therapies
• Renin-Angiotensin-Aldosterone System Inhibitors
• Class IIa
– ACEI reasonable for all patients with STEMI (LOE:A)
2013 ACCF/AHA STEACS Circulation. 2013;127:529-555
Routine Medical Therapies: STEMI
• Lipid Management
• Class I
– High-intensity statin therapy should be initiated or
continued in all patients with STEMI and no
contraindications to its use. (LOE: B)
• Class IIa
– It is reasonable to obtain a fasting lipid profile in patients
with STEMI, preferably within 24 hours of presentation.
(LOE: C)
2013 ACCF/AHA STEACS Circulation. 2013;127:529-555
Secondary Prevention Following MI
1. Aspirin: For both STEMI and Non-ST-segment elevation ACS
indefinitely.
Homework: dose recommended?
2. Clopidogrel/Prasugrel: As described earlier.
Homework: check doses, duration and interaction with PPI’s
3. Anticoagulation:
Warfarin should be considered in selected patients following an
ACS:
1. Patients with a left ventricular thrombus
2. Patients demonstrating extensive ventricular wall motion
abnormalities on cardiac echocardiogram
3. Patients with a history of thromboembolic disease
4. Chronic atrial fibrillation.
Many drug & food interactions (review)
Secondary Prevention Following MI
4. Beta-blockers:
All patients with ACS should receive Beta-blockers
indefinitely unless contraindicated.
5. ACE-Is:
STEMI: It is recommended to start early within 24 hours
and continue indefinitely.
Non-ST-segment elevation ACS: It is recommended for
patients with
 Heart failure,
 Left ventricular dysfunction,
 Ejection fraction < 40%, hypertension,
 Diabetes mellitus,
 Coronary artery disease
ARB’s (candesartan and valsartan)  alternatives
Secondary Prevention Following MI
6. Lipid Lowering Agents
– There are now overwhelming data supporting the
benefits of statins in patients with coronary artery
disease in the prevention of total mortality,
cardiovascular mortality, and stroke.
– Although the primary effect of statins is to decrease
LDL cholesterol, statins are believed to produce
many non-Lipid-lowering or "pleiotropic" effects.
– Improvement in endothelial dysfunction
– Anti-inflammatory
– Antithrombotic properties
Secondary Prevention Following MI
6. Lipid Lowering Agents
– High-dose/ or moderate-dose statin are recommended
– Whether or not a statin should be used routinely in all
patients irrespective of their baseline LDL cholesterol level is
currently being investigated:
– But preliminary data from the Heart Protection Study
suggests that patients benefit from statin therapy
irrespective of their baseline LDL cholesterol.
– Consider a fibrate or niacin in patients with a low HDL (< 40
mg/dL) or high triglycerides (> 200 mg/dL)
Secondary Prevention Following MI
7. Fish Oils (Marine-Derived Omega-3 Fatty Acids)
• The American Heart Association recommends consumption of 1g
Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for
patients with coronary heart disease (preferably from oily fish).
• Epidemiologic and randomized trials have demonstrated that a
diet high in EPA plus DHA or supplementation with these fish oils
reduces the risk of cardiovascular mortality,
reinfarction, and stroke in patients who have
experienced MI.
Secondary Prevention Following MI
7. Fish Oils (Marine-Derived Omega-3 Fatty Acids)
8. Supplements could be considered for select patients who do
not eat fish, have limited access to fish, or who cannot afford to
purchase fish. Approximately three 1 g fish oil capsules per day
should be consumed to provide 1 g omega-3 fatty acids
depending on the brand of supplement.
• current guidelines suggest that higher doses of EPA plus DHA (2
to 4 g/day) also can be considered for the management of
hypertriglyceridemia.
• Adverse effects from fish oils include fishy aftertaste, nausea,
and diarrhea.
Secondary Prevention Following MI
8. Aldosterone antagonists:
– Examples: spironolactone or eplerenone.
– Eplerenone blocks mineralocorticoid receptors and does not
affect progesterone or androgen receptors.
– Eplerenone has lower risk to produce gynecomastia, sexual
dysfunction, and menstrual irregularities compared to
spirnolactone.
– Aldosterone antagonists should be considered within the
first 2 weeks following STEMI in all patients receiving ACE-I
who have EF less or equal 40% and have heart failure
symptoms or diabetes mellitus.
Evaluation of Therapeutic Outcomes
• The monitoring parameters for efficacy of nonpharmacologic
and pharmacotherapy for both STE and NSTE ACS are similar:
– Relief of ischemic discomfort
– Return of ECG changes to baseline
– Absence or resolution of heart failure signs
• Monitoring parameters for recognition and prevention of
adverse effects from ACS pharmacotherapy;
– the most common adverse reactions to ACS therapies are
hypotension and bleeding.
– Treatment for bleeding and hypotension involves
discontinuation of the offending agent(s) until symptoms
resolve. Severe bleeding resulting in hypotension secondary
to hypovolemia may require blood transfusion.
Monitoring
Drug
Adverse Effects
Monitoring
Aspirin
Dyspepsia, bleeding, gastritis
Clinical signs of bleeding,a gastrointestinal upset;
baseline CBC and platelet count; CBC platelet count
every 6 months
Clopidogreland prasugrel Bleeding, diarrhea, rash, TTP (rare) Clinical signs of bleedinga; baseline CBC and platelet
count; CBC and platelet count every 6 months
following hospital discharge
Unfractionatedheparin
Bleeding, heparin-induced
thrombocytopenia
Clinical signs of bleedinga; baseline aPTT, INR, CBC
and platelet count; aPTT every 6 hours until target
then every 24 hours; daily CBC; platelet count every
2–3 days from day 4 to 14 until heparin is stopped
(minimum, preferably every day)
Enoxaparin
Bleeding, heparin- induced
thrombocytopenia
Clinical signs of bleedinga; baseline SCr, aPTT, INR, CBC
and platelet count; daily CBC, no routine platelet
count monitoring unless recent UFH (less than 100
days) then baseline and within 24 hours; daily CBC
and SCr
Fondaparinux
Bleeding
Clinical signs of bleedinga; baseline SCr, aPTT, INR, CBC
and platelet count; daily CBC and SCr
Bivalirudin
Bleeding
Clinical signs of bleedinga; baseline SCr, aPTT, INR, CBC
and platelet count; daily CBC and SCr
Fibrinolytics
Bleeding, especially intracranial
hemorrhage
Clinical signs of bleedinga; baseline aPTT, INR, CBC
and platelet count; mental status every 2 hours for
signs of intracranial hemorrhage; daily CBC
Drug
Adverse Effects
Monitoring
Glycoprotein IIb/IIIa
receptor blockers
Bleeding, acute profound
thrombocytopenia
Clinical signs of bleedinga; baseline SCr
(for eptifibatide and tirofiban), CBC, and platelet
count; platelet count at 4 hours after initiation; daily
CBC (and SCr for eptifibatide and tirofiban)
Intravenous nitrates
Hypotension, flushing, headache,
tachycardia
BP and HR every 2 hours
B-Blockers
Hypotension, bradycardia, heart
block, bronchospasm, acute heart
failure, fatigue, depression, sexual
dysfunction
BP, RR, HR, 12-lead ECG and clinical signs of heart
failure every 5 minutes during bolus intravenous
dosing; BP, RR, HR, and clinical signs of heart failure
every shift during oral administration during
hospitalization, then BP and HR every 6 months
following hospital discharge
Diltiazem andverapamil
Hypotension, bradycardia, heart
block, heart failure, gingival
hyperplasia
BP and HR every shift during oral administration
during hospitalization then every 6 months following
hospital discharge; dental exam and teeth cleaning
every 6 months
Amlodipine
Hypotension, dependent
peripheraledema, gingival
hyperplasia
BP every shift during oral administration during
hospitalization, then every 6 months following
hospital discharge; dental exam and teeth cleaning
every 6 months
Drug
Adverse Effects
Monitoring
Angiotensinconvertingenzyme (ACE)
inhibitors and angiotensin
receptor blockers (ARBs)
Hypotension, cough (with ACE
inhibitors),hyperkalemia,
prerenal azotemia, acute renal
failure,angioedema (ACE
inhibitors more so than ARBs)
BP every 2 hours ⋉ 3 for first dose, then every shift during
oral administration during hospitalization, then once every 6
months following hospital discharge; baseline SCr
and potassium; daily SCr and potassiumwhile hospitalized
then every 6 months (or 1–2 weeks after each outpatient
dose titration); closer monitoring required in selected
patients usingspironolactone or eplerenone or if renal
insufficiency; counsel patient on throat, tongue, and facial
swelling
Aldosterone antagonists
Hypotension, hyperkalemia
BP and HR every shift during oral administration during
hospitalization, then once every 6 months; baseline SCr and
serum potassium concentration; SCr and potassium at 48
hours, at 7 days, then monthly for 3 months, then every 3
months thereafter following hospital discharge
Warfarin
Bleeding, skin necrosis
Clinical signs of bleedinga ; baseline CBC and platelet count;
CBC and platelet count every 6 months following hospital
discharge; baseline aPTT and INR; daily INR until two
consecutive INRs are within the target range then once
weekly ⋉ 2 weeks, then every month; See Chapter 26 for
patient counseling points
Morphine
Hypotension, respiratory
depression
BP and RR 5 minutes after each bolus dose
Statins
Gastrointestinal upset,
myopathy, hepatotoxicity
Liver function tests at baseline, at 6 weeks following
initiation, and after titration to highest dose, then annually
thereafter; counsel patient on myalgia; consider creatinine
kinase at baseline if adding a fibrate or niacin
GI bleeding after PCI
• Gastrointestinal (GI) bleeding occurs in 1.2 to
2.4 percent of percutaneous coronary
intervention (PCI) patients.
• GI bleeding is associated with increased early
and late mortality, including a heightened risk of
stent thrombosis
GI bleeding after PCI
• Risk factors of GI bleeding after PCI and
antiplatelets use
•
•
•
•
•
•
•
•
•
•
•
•
advanced age
primary PCI for ST-elevation myocardial infarction,
shock or inotrope requirement,
cardiac arrest,
baseline anemia,
smoking,
diabetes,
duration of antithrombotic study drug administration,
female sex,
prior stroke,
chronic kidney disease,
history of prior bleeding or complicated peptic ulcer disease, and heart
GI bleeding after PCI
• We recommend gastrointestinal prophylaxis for
all patients undergoing PCI who are at high risk
of an adverse gastrointestinal event consequent
to therapy with aspirin and clopidogrel (or any
other P2Y12receptor blocker)
GI bleeding after PCI
• The COGENT trial tested the hypothesis that PPI therapy reduces the risk of
GI bleeding in patients on long-term dual antiplatelet therapy
with aspirin and clopidogrel [33]. In this trial, 3761 patients with an acute
coronary syndrome or undergoing percutaneous coronary intervention were
randomly assigned toomeprazole 20 mg or placebo daily. The following
findings were noted with omeprazole therapy:
• ●The primary GI end point (a composite of overt or occult GI bleeding,
symptomatic gastroduodenal ulcers or erosion, obstruction, or perforation)
was significantly reduced (1.1 versus 2.9 percent; hazard ratio 0.34, 95% CI
0.18-0.63) at 180 days.
• ●The rate of overt upper GI bleeding was significantly reduced (hazard ratio
0.13, 95% CI 0.03-0.56).
GI bleeding after PCI
• There was no negative impact of omeprazole therapy on the
primary composite cardiovascular end point in the COGENT trial
(hazard ratio 0.99, 95% CI 0.68-1.44), despite some concern
from observational studies that PPIs might have an adverse
effect on cardiovascular outcomes in patients treated
with clopidogrel
However, because of the small number of cardiovascular events
(109), the 95 percent confidence limits for this hazard ratio
include a 32 percent decrease in cardiovascular events as well as
a 44 percent increase in such events, leaving open the question
of a clinically meaningful difference in cardiovascular events due
to the use of a PPI.
Interaction between omeprazole and clopidogrel
• Risk Rating D: Consider therapy modification
•
Summary Omeprazole may diminish the antiplatelet effect of
Clopidogrel. Omeprazole may decrease serum concentrations of
the active metabolite(s) of Clopidogrel. Severity Major Reliability
Rating Fair: Existing data/reports are inconsistent
•
Patient Management Clopidogrel prescribing information
recommends avoiding concurrent use with omeprazole due to the
possibility that combined use may result in decreased clopidogrel
effectiveness. Rabeprazole or pantoprazole may be lower-risk
alternatives to omeprazole.
DAPT score to predict stent thrombosis Vs. bleeding