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__NOTOC__
{{CMG}}; {{AE}} {{ATS}}; {{Rim}}
{| class="infobox" style="margin: 0 0 0 0; border: 0; float: right; width: 100px; background: #A8A8A8; position: fixed; top: 250px; right: 21px; border-radius: 0 0 10px 10px;" cellpadding="0" cellspacing="0";
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! style="padding: 0 5px; font-size: 85%; background: #A8A8A8" align=center| {{fontcolor|#2B3B44|Unstable angina/ NSTEMI Resident Survival Guide Microchapters}}
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! style="font-size: 80%; padding: 0 5px; background: #DCDCDC" align=left | [[Unstable angina/ NSTEMI resident survival guide#Overview|Overview]]
|-
! style="font-size: 80%; padding: 0 5px; background: #DCDCDC" align=left | [[Unstable angina/ NSTEMI resident survival guide#Causes|Causes]]
|-
! style="font-size: 80%; padding: 0 5px; background: #DCDCDC" align=left | [[Unstable angina/ NSTEMI resident survival guide#FIRE: Focused Initial Rapid Evaluation|FIRE]]
|-
! style="font-size: 80%; padding: 0 5px; background: #DCDCDC" align=left | [[Unstable angina/ NSTEMI resident survival guide#Complete Diagnostic Approach|Diagnosis]]
|-
! style="font-size: 80%; padding: 0 5px; background: #DCDCDC" align=left | [[Unstable angina/ NSTEMI resident survival guide#Treatment|Treatment]]
: [[Unstable angina/ NSTEMI resident survival guide#Management Following Angiography|Management Following Angiography]]
|-
! style="font-size: 80%; padding: 0 5px; background: #DCDCDC" align=left | [[Unstable angina/ NSTEMI resident survival guide#Pre-Discharge Care|Pre-Discharge Care]]
|-
! style="font-size: 80%; padding: 0 5px; background: #DCDCDC" align=left | [[Unstable angina/ NSTEMI resident survival guide#Long Term Managemnet|Long Term Management]]
|-
! style="font-size: 80%; padding: 0 5px; background: #DCDCDC" align=left | [[Unstable angina/ NSTEMI resident survival guide#Do's|Do's]]
|-
! style="font-size: 80%; padding: 0 5px; background: #DCDCDC" align=left | [[Unstable angina/ NSTEMI resident survival guide#Don'ts|Don'ts]]
|}
==Overview==
[[Unstable angina]] and [[non ST elevation myocardial infarction]] ([[NSTEMI]]) belong to two different ends of the spectrum of [[acute coronary syndrome]].  These conditions have a similar clinical presentation characterized by an acute onset of chest pain that starts on minimal exertion, rest or sleep, lasts at least 20 minutes (but usually less that half an hour) and, is not relieved by medications or rest.  [[NSTEMI]] is differentiated from [[unstable angina]] by the presence of elevated cardiac biomarkers secondary to myocardial injury. [[Unstabel angina]] and [[NSTEMI]] might not be differentiated early following the occurrence of symptoms because [[cardiac biomarker]]s may require a few hours to rise.
==Causes==
===Life Threatening Causes===
Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated.  [[Unstable angina]] and [[NSTEMI]] are life-threatening conditions and must be treated as such irrespective of the causes.
===Common Causes===
====Myocardial Infarction====
* [[Atherosclerotic]] [[plaque rupture]] and subsequent [[coronary thrombus]] (most common cause)
* [[Coronary artery spasm]]
* [[Arrhythmia]]
* [[MI|Post-myocardial infarction]]
* [[PCI|Post-percutaneous coronary intervention]]
** [[Abrupt closure]]
** [[PCI complications: loss of side branch|Loss of side branch]]
** [[Distal embolization]]
** [[PCI complications: restenosis|Restenosis]]
**[[Stent thrombosis]]
* [[CABG|Post-coronary artery bypass graft]]
** Graft closure
** New lesion in the graft
''For a complete list of causes, click [[Unstable angina pathophysiology|here]] for unstable angina and [[Non ST elevation myocardial infarction pathophysiology|here]] for NSTEMI.''
==FIRE: Focused Initial Rapid Evaluation==
==FIRE: Focused Initial Rapid Evaluation==
A Focused Initial Rapid Evaluation (FIRE) should be performed to identify patients in need of immediate intervention based on the 2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non-ST-elevation myocardial infarction.<ref name="pmid22809746">{{cite journal| author=Jneid H, Anderson JL, Wright RS, Adams CD, Bridges CR, Casey DE et al.| title=2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non-ST-elevation myocardial infarction (updating the 2007 guideline and replacing the 2011 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. | journal=J Am Coll Cardiol | year= 2012 | volume= 60 | issue= 7 | pages= 645-81 | pmid=22809746 | doi=10.1016/j.jacc.2012.06.004 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22809746  }} </ref>
A Focused Initial Rapid Evaluation (FIRE) should be performed to identify patients in need of immediate intervention based on the 2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non-ST-elevation myocardial infarction.<ref name="pmid22809746">{{cite journal| author=Jneid H, Anderson JL, Wright RS, Adams CD, Bridges CR, Casey DE et al.| title=2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non-ST-elevation myocardial infarction (updating the 2007 guideline and replacing the 2011 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. | journal=J Am Coll Cardiol | year= 2012 | volume= 60 | issue= 7 | pages= 645-81 | pmid=22809746 | doi=10.1016/j.jacc.2012.06.004 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22809746  }} </ref> An invasive strategy is defined as diagnostic angiography with the intention of revascularization.


<span style="font-size:85%">Boxes in the red color signify that an urgent management is needed.</span>
<span style="font-size:85%">Boxes in the red color signify that an urgent management is needed.</span>
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{{Family tree/start}}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF;  | | | | A00 | | A00=<div style="float: left; text-align: left; width: 20em; padding:1em;"> '''Identify cardinal findings of unstable angina/ NSTEMI :''' <br>
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF;  | | | | A00 | | A00=<div style="float: left; text-align: left; width: 17em; padding:1em;"> '''Identify cardinal findings of unstable angina/ NSTEMI :''' <br>
❑ '''[[Chest pain|<span style="color:white;"> Chest pain</span>]] or [[chest discomfort|<span style="color:white;">chest discomfort</span>]]''' <br>
❑ '''[[Chest pain|<span style="color:white;"> Chest pain</span>]] or [[chest discomfort|<span style="color:white;">chest discomfort</span>]]''' <br>
:❑ Sudden onset
:❑ Sudden onset
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:❑ Flipped or inverted T waves <br>
:❑ Flipped or inverted T waves <br>
:❑ ST depression (carries the poorest prognosis) <br>
:❑ ST depression (carries the poorest prognosis) <br>
❑ '''Increase in >99th percentile of upper limit of normal of [[troponin|<span style="color:white;">troponin</span>]] and / or [[CKMB|<span style="color:white;">CK MB </span>]]''', which is consistent with [[NSTEMI|<span style="color:white;">NSTEMI</span>]]</div>}}
❑ '''Increase in >99th percentile of upper limit of normal of [[troponin|<span style="color:white;">troponin</span>]] and / or [[CKMB|<span style="color:white;">CK MB</span>]]''', which is consistent with [[NSTEMI|<span style="color:white;">NSTEMI</span>]]</div>}}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF;  | | | | |!| | | }}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF;  | | | | |!| | | }}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF;  | | | | G02 | G02= <div style="float: left; text-align: left; width: 20em; padding:1em;"> '''Rule out life threatening alternative diagnoses:'''<br>
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF;  | | | | G02 | G02= <div style="float: left; text-align: left; width: 17em; padding:1em;"> '''Rule out life threatening alternative diagnoses:'''<br>
❑ [[Aortic dissection|<span style="color:white;">Aortic dissection</span>]] <br> (suggestive findings: [[back pain|<span style="color:white;">back pain</span>]], [[interscapular pain|<span style="color:white;">interscapular pain</span>]], [[aortic regurgitation|<span style="color:white;">aortic regurgitation</span>]], [[pulsus paradoxus|<span style="color:white;">pulsus paradoxus</span>]], [[blood pressure|<span style="color:white;">blood pressure</span>]] discrepancy between the arms) <br>
❑ [[Aortic dissection|<span style="color:white;">Aortic dissection</span>]] <br> (suggestive findings: [[back pain|<span style="color:white;">back pain</span>]], [[interscapular pain|<span style="color:white;">interscapular pain</span>]], [[aortic regurgitation|<span style="color:white;">aortic regurgitation</span>]], [[pulsus paradoxus|<span style="color:white;">pulsus paradoxus</span>]], [[blood pressure|<span style="color:white;">blood pressure</span>]] discrepancy between the arms) <br>
❑ [[Pulmonary embolism|<span style="color:white;">Pulmonary embolism</span>]] <br> (suggestive findings: acute onset of [[dyspnea|<span style="color:white;">dyspnea</span>]], [[tachypnea|<span style="color:white;">tachypnea</span>]], [[hemoptysis|<span style="color:white;">hemoptysis</span>]], previous [[DVT|<span style="color:white;">DVT</span>]]) <br>
❑ [[Pulmonary embolism|<span style="color:white;">Pulmonary embolism</span>]] <br> (suggestive findings: acute onset of [[dyspnea|<span style="color:white;">dyspnea</span>]], [[tachypnea|<span style="color:white;">tachypnea</span>]], [[hemoptysis|<span style="color:white;">hemoptysis</span>]], previous [[DVT|<span style="color:white;">DVT</span>]]) <br>
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❑ [[Esophageal rupture|<span style="color:white;">Esophageal rupture</span>]] <br> (suggestive findings: [[vomiting|<span style="color:white;">vomiting</span>]], [[subcutaneous emphysema|<span style="color:white;">subcutaneous emphysema</span>]])</div>}}
❑ [[Esophageal rupture|<span style="color:white;">Esophageal rupture</span>]] <br> (suggestive findings: [[vomiting|<span style="color:white;">vomiting</span>]], [[subcutaneous emphysema|<span style="color:white;">subcutaneous emphysema</span>]])</div>}}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF;  | | | | |!| | | }}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF;  | | | | |!| | | }}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF;  | | | | A01 | | | | | A01= <div style="float: left; text-align: left; width: 20em; padding:1em;">'''Begin initial treatment:'''<br> ❑ Administer [[aspirin|<span style="color:white;">aspirin</span>]] (I-A)
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF;  | | | | A01 | | | | | A01= <div style="float: left; text-align: left; width: 17em; padding:1em;">'''Begin initial treatment:'''<br>  
:❑ 162 to 325 mg of non enteric [[aspirin|<span style="color:white;">aspirin</span>]],orally, crushed or chewed, THEN
❑ Administer 162 to 325 mg of non enteric [[aspirin|<span style="color:white;">aspirin</span>]],orally, crushed or chewed (I-A)
:❑ 75 to 325 mg/day
:''Among patients with either GI intolerance or hypersensitivity to aspirin, administer a loading dose (75 mg) followed by maintenance dose of clopidogrel (I-B)''
:''Among patients with either GI intolerance or hypersensitivity to aspirin, administer a loading dose followed by maintenance dose of either clopidogrel (I-B), or prasugrel in PCI patients (I-C), or ticagrelor (I-C)''
❑ Administer 2-4 L/min [[oxygen|<span style="color:white;">oxygen</span>]] via nasal cannula when saturation <90% (I-C)
❑ Administer 2-4 L/min [[oxygen|<span style="color:white;">oxygen</span>]] via nasal cannula when saturation <90%
:''Caution in [[COPD|<span style="color:white;">COPD</span>]] patients: maintain an oxygen saturation between 88% and 92%.''
:Caution in [[COPD|<span style="color:white;">COPD</span>]] patients: maintain an oxygen saturation between 88% and 92%
❑ Administer [[nitroglycerin|<span style="color:white;">nitroglycerin</span>]]
❑ Administer [[beta-blockers|<span style="color:white;">beta-blockers</span>]] (unless contraindicated) and titrate to the [[heart rate|<span style="color:white;">heart rate</span>]] and [[blood pressure|<span style="color:white;">blood pressure </span>]]<br>
:❑ Administer sublingual nitroglycerin (0.3 to 0.4 mg, every 5 minutes for a total of 3 doses) then assess for further need to IV nitroglycerin (I-C)
<span style="font-size:85%;">Contraindicated in [[heart failure|<span style="color:white;">heart failure </span>]], [[AV block |<span style="color:white;">prolonged or high degree AV block </span>]], [[reactive airway disease|<span style="color:white;">reactive airway disease </span>]], high risk of [[cardiogenic shock|<span style="color:white;">cardiogenic shock </span>]] and low [[cardiac output|<span style="color:white;">cardiac output</span>]] state</span> <br>
:❑ Administer IV nitroglyerin in case of persistent chest pain despite PO nitroglycerin, heart failure, or hypertenion (I-B): 10 mcg/min, increase by 10 mcg/min every 3 to 5 minutes until symptom relief; in case no response at 20 mcg/min, can increase by 10 mcg/min and then by 20 mcg/min
:❑ [[Metoprolol|<span style="color:white;">Metoprolol</span>]] IV, 5 mg every 5 min, up to 3 doses, then 25 to 50 mg orally every 6 hours
<span style="font-size:85%;">Contraindicated in suspected [[RVMI|<span style="color:white;">right ventricular MI</span>]], recent use of [[phosphodiesterase inhibitors|<span style="color:white;">phosphodiesterase inhibitors</span>]], decreased [[blood pressure|<span style="color:white;">blood pressure</span>]] 30 mmHg below baseline</span> <br>
❑ Administer [[beta-blockers|<span style="color:white;">beta-blockers</span>]] (unless contraindicated) and titrate to the [[heart rate|<span style="color:white;">heart rate</span>]] and [[blood pressure|<span style="color:white;">blood pressure</span>]] (I-A)<br>
: ''PO in general, IV if patient has hypertension or ongoing pain''
: ''Beta blocker is contraindicated in heart failure and high risk of cardiogenic shock.''
:❑ [[Metoprolol|<span style="color:white;">Metoprolol</span>]]:
:PO: 25 to 50 mg every 6 hours
:IV: 5 mg every 5 min, up to 3 doses, then 25 to 50 mg orally every 6 hours
:❑ [[Carvedilol|<span style="color:white;">Carvedilol</span>]] IV, 25 mg, two times a day
:❑ [[Carvedilol|<span style="color:white;">Carvedilol</span>]] IV, 25 mg, two times a day
❑ Administer sublingual [[nitroglycerin|<span style="color:white;">nitroglycerin</span>]] 0.4 mg every 5 minutes for a total of 3 doses<br>
<span style="font-size:85%;">Contraindicated in [[heart failure|<span style="color:white;">heart failure</span>]], bradycardia, hypotension (SBP<90 mmHg), [[AV block |<span style="color:white;">second or third degree AV block</span>]], [[reactive airway disease|<span style="color:white;">reactive airway disease</span>]], high risk of [[cardiogenic shock|<span style="color:white;">cardiogenic shock</span>]] and low [[cardiac output|<span style="color:white;">cardiac output</span>]] state</span> <br>
<span style="font-size:85%;">Contraindicated in suspected [[RVMI|<span style="color:white;">right ventricular MI </span>]], recent use of [[phosphodiesterase inhibitors|<span style="color:white;">phosphodiesterase inhibitors </span>]], decreased [[blood pressure|<span style="color:white;">blood pressure </span>]] 30 mmHg below baseline</span> <br>
❑ Administer IV [[morphine|<span style="color:white;">morphine</span>]] if persistent symptoms (IIb-B) or [[pulmonary edema|<span style="color:white;">pulmonary edema</span>]]
❑ Administer IV [[morphine|<span style="color:white;">morphine</span>]] if persistent symptoms or [[pulmonary edema|<span style="color:white;">pulmonary edema</span>]]
:❑ Initial dose 4-8 mg
:❑ Initial dose 4-8 mg
:❑ 2-8 mg every 5 to 15 minutes, as needed <br>
:❑ 2-8 mg every 5 to 15 minutes, as needed <br>
❑ Administer 80 mg [[atorvastatin|<span style="color:white;">atorvastatin</span>]] <br>
❑ Administer 80 mg [[atorvastatin|<span style="color:white;">atorvastatin</span>]] (I-A)<br>
❑ Monitor with a 12-lead [[ECG|<span style="color:white;">ECG</span>]] all the time
❑ Monitor with a 12-lead [[ECG|<span style="color:white;">ECG</span>]] all the time
</div>}}
</div>}}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF;  | | | | |!| | | }}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF;  | | | | |!| | | }}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF;  | | | | G01 | G01= <div style="float: left; text-align: left; width: 20em; padding:1em;"> '''Does the patient have any of the following indications that require immediate angiography and revascularization ?'''
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF;  | | | | G01 | G01= <div style="float: left; text-align: left; width: 17em; padding:1em;"> {{fontcolor|#000000|'''TRIAGE FOR IMMEDIATE INTERVENTION'''}} <br>'''Does the patient have ANY of the following indications that require immediate angiography and revascularization ?'''
❑ Hemodynamic instability or [[cardiogenic shock|<span style="color:white;">cardiogenic shock </span>]] <br>
❑ Hemodynamic instability or [[cardiogenic shock|<span style="color:white;">cardiogenic shock</span>]], '''OR''' <br>
❑ Severe left ventricular dysfunction or [[heart failure|<span style="color:white;">heart failure </span>]] <br>
❑ Severe left ventricular dysfunction or [[heart failure|<span style="color:white;">heart failure</span>]], '''OR'''  <br>
❑ Recurrent or persistent rest angina despite intensive medical therapy <br>
❑ Recurrent or persistent rest angina despite intensive medical therapy, '''OR'''  <br>
❑ New or worsening [[mitral regurgitation|<span style="color:white;">mitral regurgitation </span>]] or new [[VSD|<span style="color:white;">VSD </span>]] <br>
❑ New or worsening [[mitral regurgitation|<span style="color:white;">mitral regurgitation</span>]] or new [[VSD|<span style="color:white;">VSD</span>]], '''OR'''  <br>
❑ Sustained [[VT|<span style="color:white;">VT </span>]] or [[VF|<span style="color:white;">VF </span>]]<br>
❑ Sustained [[VT|<span style="color:white;">VT</span>]] or [[VF|<span style="color:white;">VF</span>]], '''OR''' <br>
❑ Prior [[PCI|<span style="color:white;">PCI </span>]] within past 6 months or [[CABG|<span style="color:white;">CABG </span>]] <br> </div> }}
❑ Prior [[PCI|<span style="color:white;">PCI</span>]] within past 6 months or [[CABG|<span style="color:white;">CABG</span>]] <br> </div> }}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | |,|-|-|^|-|-|.| | }}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | |,|-|-|^|-|-|.| | }}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | C01 | | | | C02 | | | C01=<div style="float: left; text-align: center; width: 20em; padding:1em;">'''YES''' </div>| C02= <div style="float: left; text-align: center; width: 20em; padding:1em;">'''NO''' </div> }}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | C01 | | | | C02 | | | C01=<div style="float: left; text-align: center; width: 17em; padding:1em;">'''YES''' </div>| C02= <div style="float: left; text-align: center; width: 17em; padding:1em;">'''NO''' </div> }}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | |!| | | | | |!| | | | }}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | |!| | | | | |!| | | | }}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | |!| | | | | C03 | | | C03=<div style="float: left; text-align: left; width: 20em; padding:1em;">Does the patient have negative ECG findings AND negative biomarkers?</div>}}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | |!| | | | | C03 | | | C03=<div style="float: left; text-align: left; width: 17em; padding:1em;">Does the patient have no ECG changes '''AND''' no rise in cardiac biomarkers > 99th percentile of ULN?</div>}}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | |!| | | |,|-|^|-|.| | }}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | |!| | | |,|-|^|-|.| | }}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | |!| | | C04 | | C05 |  C04= Yes | C05= No}}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | |!| | | C04 | | C05 |  C04= <div style="float: left; text-align: left; width: 17em; padding:1em;">Yes. The patient has no ECG changes AND no rise in cardiac biomarkers > 99th percentile of ULN. </div>| C05= <div style="float: left; text-align: left; width: 17em; padding:1em;">No. The patient has either positive ECG changes, OR rise in cardiac biomarkers, OR both. </div>}}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | |!| | | |!| | | |!| | }}  
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | |!| | | |!| | | |!| | }}  
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | |!| | | C06 | | |!| | C06= Repeat ECG and biomarkers within next 6 hours and 12 hours}}  
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | |!| | | C06 | | |!| | C06= <div style="float: left; text-align: left; width: 17em; padding:1em;">Repeat ECG and biomarkers within next 3 hours and 6 hours <br><br> '''Does the patient still have no ECG changes '''AND''' no rise in cardiac biomarkers?'''</div>}}  
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | |!| |,|^|-|-|.| |!| }}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | |!| |,|^|-|-|.| |!| }}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | |!| C07 | | C08 |!| C07= ECG and biomarkers are both negative | C08= At least one (ECG or biomarkers) is positive}}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | |!| C07 | | C08 |!| C07= <div style="float: left; text-align: left; width: 17em; padding:1em;">Yes. The patient has no ECG changes AND no rise in cardiac biomarkers.</div>| C08= <div style="float: left; text-align: left; width: 17em; padding:1em;">No. The patient has either positive ECG changes, OR rise in cardiac biomarkers, OR both.</div>}}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | |!| |!| | | |!| |!| }}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | |!| |!| | | |!| |!| }}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | |!|C09  | | | C10 | | | C09= <div style="float: left; text-align: left; width: 20em; padding:1em;">[[Chest pain resident survival guide#Complete Diagnostic Approach|Proceed to complete diagnostic approach of chest pain to rule out differential diagnoses]]</div>| C10=<div style="float: left; text-align: left; width: 20em; padding:1em;">'''Calculate the risk of future adverse clinical outcomes:'''<br>
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | |!|C09  | | | C10 | | | C09= <div style="float: left; text-align: left; width: 17em; padding:1em;">[[Chest pain resident survival guide#Complete Diagnostic Approach|Proceed to complete diagnostic approach of chest pain to rule out differential diagnoses]]</div>| C10=<div style="float: left; text-align: left; width: 17em; padding:1em;">{{fontcolor|#000000|''' TRIAGE FOR INITIAL CONSERVATIVE OR INVASIVE THERAPY'''}} <br>'''Calculate the risk of future adverse clinical outcomes:'''<br>
❑ [[TIMI risk score|<span style="color:white;">Thrombolysis in Myocardial Infarction (TIMI) risk score</span>]], OR
❑ [[TIMI risk score|<span style="color:white;">Thrombolysis in Myocardial Infarction (TIMI) risk score</span>]], '''OR'''
❑ [[GRACE score|<span style="color:white;">GRACE score</span>]] </div>}}
❑ [[GRACE score|<span style="color:white;">GRACE score</span>]] </div>}}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | |!| | | |,|-|-|^|.| | }}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | |!| | | |,|-|-|^|.| | }}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | |!| | | C11 | | C12 | C11=  '''Intermediate or high risk''' | C12= '''Low risk'''}}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | |!| | | C11 | | C12 | C11=  '''Intermediate or high risk''' | C12= '''Low risk'''}}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | |!| | | |!| | | |!| | }}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | |!| | | |!| | | |!| | }}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | D01 | | D02 | | D03 | |D01=<div style="float: left; text-align: center; width: 20em; padding:1em;"> '''IMMEDIATE  initial invasive strategy'''<br></div>
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | D01 | | D02 | | D03 | |D01=<div style="float: left; text-align: center; width: 17em; padding:1em;"> '''INITIAL INVASIVE THERAPY (IMMEDIATELY)'''<br></div>
| D02= <div style="float: left; text-align: center; width: 20em; padding:1em;">'''Initial invasive strategy (4 to 48 hours)''' </div>| D03= <div style="float: left; text-align: center; width: 20em; padding:1em;"> '''Initial conservative strategy''' </div>}}
| D02= <div style="float: left; text-align: center; width: 17em; padding:1em;">'''INITIAL INVASIVE THERAPY (4 to 48 hours)''' </div>| D03= <div style="float: left; text-align: center; width: 17em; padding:1em;"> '''INITIAL CONSERVATIVE THERAPY ''' </div>}}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | | |!| |!| | | | |!| | }}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | | |!| |!| | | | |!| | }}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | | | E02 | | | | E03 | |E02=<div style="float: left; text-align: left; width: 20em; padding:1em;">'''Initiate ONE of the following anticoagulant therapy (I-A)'''<br>  
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | | | E02 | | | | E03 | |E02=<div style="float: left; text-align: left; width: 17em; padding:1em;">'''Initiate ONE of the following anticoagulant therapy (I-A)'''<br>  
❑ Enoxaparin (I-A), '''OR''' <br>
❑ Enoxaparin (I-A)<br>
❑ [[UFH|<span style="color:white;">Unfractionated heparin</span>]] <br>
:❑ SC 1 mg/kg every 12 hours if CrCL≥ 30 mL/min
:♦ ''If GP IIb/IIIa receptor antagonist is planned''
:❑ SC 1 mg/kg every 12 hours if CrCL< 30 mL/min
:❑ 50- to 70-U/kg IV bolus <br>
:❑ Initial IV 30 mg loading dose in selected patients
:♦ ''If no GP IIb/IIIa receptor antagonist is planned''
'''OR''' <br>
:❑ 70- to 100-U/kg bolus <br>, '''OR'''<br>
IV [[UFH|<span style="color:white;">Unfractionated heparin</span>]] (and adjust dose for apTT) for 48 hours or until PCI is perfomed (I-B)<br>
:❑ Initial loading dose 60 IU/kg (max 40,000 IU) <br>
:❑ Initial infusion 12 IU/kg/h (max 10,000 IU)<br>'''OR''' <br>
❑ [[Bivalirudin|<span style="color:white;">Bivalirudin</span>]] (I-B)
❑ [[Bivalirudin|<span style="color:white;">Bivalirudin</span>]] (I-B)
::❑ 0.75-mg/kg IV bolus, then 1.75–mg/kg/h infusion
::❑ Loading dose 0.1-mg/kg IV bolus, then 0.25–mg/kg/h infusion
::❑ Additional bolus of 0.3 mg/kg if needed
<br>'''OR''' <br>
::❑ Decrease infusion to 1 mg/kg/h when [[creatinine|<span style="color:white;">creatinine</span>]] clearance <30 mL/min, '''OR'''<br>
❑ Fondaparinux , SC 2.5 mg daily (I-B)
❑ Fondaparinux (I-B), '''OR'''<br>
<br><br>'''PLUS'''<br><br>
<br> <br>
'''Administer ONE of the following antiplatelet agents (before OR at the time of PCI) (I-A)'''<br>
'''Administer ONE of the following antiplatelet agents (before OR at the time of PCI) (I-A)'''<br>
'''Before [[PCI|<span style="color:white;">PCI </span>]]'''<br>
❑ Loading dose of [[P2Y12|<span style="color:white;">P2Y12</span>]] receptor inhibitors <br>
❑ Loading dose of [[P2Y12|<span style="color:white;">P2Y12 </span>]] receptor inhibitors <br>
:❑ [[Clopidogrel|<span style="color:white;">Clopidogrel</span>]] (I-B if before PCI, I-A if at time of PCI)
:❑ [[Clopidogrel|<span style="color:white;">Clopidogrel </span>]] (600 mg) (I-B), '''''OR'''''<br>
::Loading dose: 300 mg or 600 mg
:❑ [[Ticagrelor|<span style="color:white;">Ticagrelor </span>]](180 mg) (I-B)<br>
:: Maintenance dose: 75 mg OD
'''''OR'''''<br>
<br>'''OR''' <br>
❑ IV [[GP IIb/IIIa|<span style="color:white;">GP IIb/IIIa </span>]] inhibitors (I-A)<br>
:❑ [[Ticagrelor|<span style="color:white;">Ticagrelor</span>]] (I-B)
:❑ [[Eptifibatide|<span style="color:white;">Eptifibatide </span>]]<br>
::Loading dose: 180 mg
::❑ Loading dose 180 mcg/kg IV bolus followed by another bolus after 10 minutes<br>
:: Maintenance dose: 90 mg BID
::❑ Maintenance dose 2 mcg/kg/min, '''''OR''''' <br>
<br>'''OR''' <br>
:❑ [[Tirofiban|<span style="color:white;">Tirofiban </span>]]<br>
:❑ Prasugrel ONLY AT THE TIME OF PCI, AND NOT PRE-PCI (I-B)<br>
::Loading dose 25 mcg/kg<br>
::Loading dose: 60 mg
::Maintenance dose 0.15 mcg/kg/min<br>
:: Maintenance dose: 10 mg OD
<br>'''''OR'''''<br>
<span style="font-size:85%;">Prasugrel is contraindicated in case of prior history of strokes or TIAs, active pathological bleeding, age ≥75 years, when urgent coronary artery bypass graft surgery (CABG) is likely, body weight <60 kg, propensity to bleed, concomitant use of medications that increase the risk of bleeding</span><br><br>
'''At the time of [[PCI|<span style="color:white;">PCI </span>]]'''<br>
'''Consider adding IV [[GP IIb/IIIa|<span style="color:white;">GP IIb/IIIa</span>]] inhibitors in case of high risk patients (IIb-B)'''<br>
❑ Loading dose of [[P2Y12|<span style="color:white;">P2Y12 </span>]] receptor inhibitors <br>
❑ [[Eptifibatide|<span style="color:white;">Eptifibatide</span>]]<br>
:❑ [[Clopidogrel|<span style="color:white;">Clopidogrel </span>]] (600 mg) (I-A), '''''OR'''''<br>
:❑ Loading dose 180 mcg/kg IV bolus followed by another bolus after 10 minutes<br>
:❑ [[Ticagrelor|<span style="color:white;">Ticagrelor </span>]] (180 mg) (I-B), '''''OR''''' <br>
:❑ Maintenance dose 2 mcg/kg/min<br>'''OR''' <br>
:❑ Prasugrel (60 mg) (I-B)<br>
❑ [[Tirofiban|<span style="color:white;">Tirofiban</span>]] <br>
<span style="font-size:85%;">Prasugrel is contraindicated in case of prior history of strokes or TIAs, active pathological bleeding, age ≥75 years, when urgent coronary artery bypass graft surgery (CABG) is likely, body weight <60 kg, propensity to bleed, concomitant use of medications that increase the risk of bleeding </span> <br>
:❑ Loading dose 25 mcg/kg<br>
'''''OR'''''<br>
:❑ Maintenance dose 0.15 mcg/kg/min </div>
IV [[GP IIb/IIIa|<span style="color:white;">GP IIb/IIIa </span>]] inhibitors (I-A)<br>
|E03=<div style="float: left; text-align: left; width: 17em; padding:1em;">'''Initiate ONE of the following anticoagulant therapy (I-A)'''<br>
:❑ [[Eptifibatide|<span style="color:white;">Eptifibatide </span>]]<br>
❑ Enoxaparin (I-A)<br>'''OR''' <br>
::❑ Loading dose 180 mcg/kg IV bolus followed by another bolus after 10 minutes<br>
❑ UFH (I-B)<br>'''OR''' <br>
::❑ Maintenance dose 2 mcg/kg/min, '''''OR''''' <br>
❑ Fondaparinux (I-B)
:❑ [[Tirofiban|<span style="color:white;">Tirofiban</span>]] <br>
::❑ Loading dose 25 mcg/kg<br>
::❑ Maintenance dose 0.15 mcg/kg/min </div>
|E03=<div style="float: left; text-align: left; width: 20em; padding:1em;">'''Initiate ONE of the following anticoagulant therapy (I-A)'''<br>
❑ Enoxaparin (I-A), '''OR''' <br>
❑ UFH (I-A), '''OR'''<br>
❑ Fondaparinux (I-B), '''OR'''<br>
:''Enoxaparin or fondaparinux preferred over UFH (II-B)''


<br><br> '''PLUS'''<br><br>
'''Administer ONE of the following antiplatelet agents (I-B):'''<br>
'''Administer ONE of the following antiplatelet agents (I-B):'''<br>
❑ [[Clopidogrel|<span style="color:white;">Clopidogrel </span>]] (I-B)<br>
:❑ Loading dose (300 mg)<br>
:❑ Maintenance dose for up to 12 months (75 mg)<br>
❑ [[Ticagrelor|<span style="color:white;">Ticagrelor </span>]] (I-B)
:❑ Loading dose (180 mg)<br>
:❑ Maintenance dose for up to 12 months (90 mg twice daily)</div>}}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | | | | | | | | | |!| | }}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | | | | | | | | | F01 | |F01='''Does the patient experience any of the following?''' <br>
❑ Recurrence of symptoms<br>
❑ [[Heart failure|<span style="color:white;">Heart failure</span>]]<br>
❑ Serious [[arrhythmia|<span style="color:white;">arrhythmia</span>]]<br>
❑ Subsequent ischemia<br>}}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | | | | | | |,|-|-|^|.| }}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | | | | | | G01 | | G02 | G01= Yes| G02= No}}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | | | | | | |!| | | |!| }}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | | | | | | H01 | | H02 |  H01= <div style="float: left; text-align: left; width: 20em; padding:1em;"> ❑ Perform diagnostic [[angiography]] (I-A)<br>
-----
Administer upstream antiplatelet agent:<br>
❑ [[P2Y12]] receptor inhibitors <br>
❑ [[P2Y12]] receptor inhibitors <br>
:❑ [[Clopidogrel]]<br>
:❑ [[Clopidogrel]]<br>
::❑ Loading dose (600 mg)<br>
::❑ Loading dose (300 mg or 600 mg)<br>
::❑ Maintenance dose (75 mg), or<br>
::❑ Maintenance dose (75 mg)<br>'''OR''' <br>
:❑ [[Ticagrelor]]<br>
:❑ [[Ticagrelor]]<br>
::❑ Loading dose (180 mg)<br>
::❑ Loading dose (180 mg)<br>
::❑ Maintenance dose (90 mg twice daily), or<br>
::❑ Maintenance dose (90 mg twice daily)<br>'''OR''' <br>
❑ IV [[GP IIb/IIIa]] inhibitors <br>
</div>}}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | | | |!| | | | | |!| | }}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | | | |!| | | | | F01 | |F01=<div style="float: left; text-align: left; width: 17em; padding:1em;">{{fontcolor|#000000|'''TRIAGE FOR NEED OF INVASIVE THERAPY'''}} <br>'''Does the patient experience ANY of the following?''' <br>
❑ Recurrence of symptoms, OR<br>
❑ [[Heart failure|<span style="color:white;">Heart failure</span>]], OR<br>
❑ Serious [[arrhythmia|<span style="color:white;">arrhythmia</span>]], OR<br>
❑ Subsequent ischemia</div>}}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | | | |!| |,|-|-|-|^|.| }}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | | | |!| G01 | | G02 | G01= YES| G02= NO}}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | | | |!| |!| | | |!| }}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | | | |!| H01 | | H02 |  H01= <div style="float: left; text-align: left; width: 17em; padding:1em;"> '''PROCEED TO INVASIVE THERAPY (I-A)''' <br>
'''Administer ONE of the following antiplatelet agents if not already administered (I-A):'''<br>
:''The antiplatelet should be administered upstream (I-C)''
❑ [[P2Y12]] receptor inhibitors <br>
:❑ [[Clopidogrel]] (I-B)<br>
::❑ Loading dose (300 mg or 600 mg)<br>
::❑ Maintenance dose (75 mg)<br>'''OR''' <br>
:❑ [[Ticagrelor]] (I-B)<br>
::❑ Loading dose (180 mg)<br>
::❑ Maintenance dose (90 mg twice daily)<br>'''OR''' <br>
❑ IV [[GP IIb/IIIa]] inhibitors (I-A)<br>
:❑ [[Eptifibatide]]<br>
:❑ [[Eptifibatide]]<br>
::❑ Loading dose 180 mcg/kg IV bolus followed by another bolus after 10 minutes<br>
::❑ Loading dose 180 mcg/kg IV bolus followed by another bolus after 10 minutes<br>
::❑ Maintenance dose 2 mcg/kg/min, or <br>
::❑ Maintenance dose 2 mcg/kg/min<br>'''OR''' <br>
:❑ [[Tirofiban]] <br>
:❑ [[Tirofiban]] <br>
::❑ Loading dose 25 mcg/kg<br>
::❑ Loading dose 25 mcg/kg<br>
::❑ Maintenance dose 0.15 mcg/kg/min<br></div>
::❑ Maintenance dose 0.15 mcg/kg/min<br></div>
| H02= ❑ Perform a [[stress test]] (I-B)}}
| H02= <div style="float: left; text-align: left; width: 17em; padding:1em;">{{fontcolor|#000000|'''TRIAGE PATIENTS BY RISK ON STRESS TEST'''}} <br>❑ Perform a [[stress test]] (I-B) </div>}}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | | | | | | | |,|-|-|^|.|}}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | | | |!|!| |,|-|-|^|.|}}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | | | | | | | I01 | | I02 | I01= '''Low risk on stress test'''| I02= '''High risk on stress test'''}}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | | | |!|!| I01 | | I02 | I01= <div style="float: left; text-align: left; width: 17em; padding:1em;">'''High risk on stress test''' </div>| I02= <div style="float: left; text-align: left; width: 17em; padding:1em;">'''Low risk on stress test OR did not undergo stress test''' </div>}}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | | | | | | | |!| | | |!| | }}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | | | |!|!| |!| | | |!| | }}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | | | | | | | |!| | | J01 | J01= ❑ Perform diagnostic [[angiography]] (I-A)}}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | | | |!|!| J01 | | |!| | J01= <div style="float: left; text-align: left; width: 17em; padding:1em;"> '''INVASIVE THERAPY''' <br>❑ Perform diagnostic [[angiography]] (I-A) </div>}}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | | | | | | | K01 | | | | | K01= <div style="float: left; text-align: left; width: 20em; padding:1em;"> ❑ Continue [[aspirin]] for life (I-A)<br> ❑ Continue [[P2Y12]] receptor inhibitors up to 12 months (I-B)<br>
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | | | |!|!|!| | | | K01 | K01= <div style="float: left; text-align: left; width: 17em; padding:1em;"> ❑ Continue [[aspirin]] for life (I-A)<br> ❑ Continue [[P2Y12]] receptor inhibitors up to 12 months (I-B)<br>
:❑ [[Clopidogrel]] (75 mg once a day), or<br>
:❑ [[Clopidogrel]] (75 mg once a day)<br>'''OR''' <br>
:❑ [[Ticagrelor]] (90 mg twice a day)<br>
:❑ [[Ticagrelor]] (90 mg twice a day)<br>
❑ Discontinue [[GP IIb/IIIa]] inhibitors (I-A)<br>
❑ Discontinue [[GP IIb/IIIa]] inhibitors if administered earlier (I-A)<br>
❑ Continue [[antithrombotic]] therapy:<br>
❑ Continue [[antithrombotic]] therapy:<br>
:❑ [[UFH]] for 48 hours (I-A), or<br>
:❑ [[UFH]] for 48 hours (I-A)<br>'''OR''' <br>
:❑ [[Enoxaparin]] for duration of hospitalization (up to 8 days) (I-A), or <br>
:❑ [[Enoxaparin]] for duration of hospitalization (up to 8 days) (I-A)<br>'''OR''' <br>
:❑ [[Fondaparinux]] for duration of hospitalization (up to 8 days) (I-B)</div>}}
:❑ [[Fondaparinux]] for duration of hospitalization (up to 8 days) (I-B)
❑ Measure LVEF (I-B)</div>}}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | | | |!|!|!| | | | | |}}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | | | | C01 | | | | | | | | C01= <div style="float: left; text-align: left; width: 17em; padding:1em;">{{fontcolor|#000000|'''TRIAGE FOR SUBSEQUENT THERAPY PLAN FOLLOWING ANGIOGRAPHY'''}} <br> Does the [[angiography]] show coronary vessel obstruction ?</div> }}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | | |,|-|^|-|-|.| | | | | }}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | | D01 | | | | D02 | | | | D01=  '''No'''| D02= '''Yes'''}}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | | |!| | | |,|-|^|-|-|-|-|-|.| | | }}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | | |!| | | E01 | | E02 | | E03 | | E01=<div style="float: left; text-align: left; width: 17em; padding:1em;">❑ 1 or 2 vessel disease <br> ''[[CABG]] or medical therapy might also be considered'' </div>|E02=<div style="float: left; text-align: left; width: 17em; padding:1em;">❑ Left main coronary artery disease <br>❑ 3 vessel disease <br>❑ 2 vessel disease with proximal left anterior descending artery affection <br>❑ [[Left ventricular dysfunction]] <br> ❑Patient treated from [[diabetes]]</div>| E03= }}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | | |!| | | |!| | | |!| | | |!| | |}}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | | L03 | | L01 | | L02 | | L03 | | L01= '''[[PCI]]''' <br>
| L02= '''[[CABG]]''' <BR>
| L03= '''Medical treatment'''}}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | | |!| | | |!| | | |!| | | |!| | | }}
{{familytree |boxstyle=background: #FA8072; color: #F8F8FF; | | M01 | | M02 | | M03 | | M04 | | M01= <div style="float: left; text-align: left; width: 17em; padding:1em;">
❑ Administer aspirin indefinitely <br>
❑ Administer additional antiplatelet therapy ''at the discretion of the physician'' (I-C)<br>
❑ Administer anticoagulant therapy ''at the discretion of the physician'' (I-C)</div>
|M02= <div style="float: left; text-align: left; width: 17em; padding:1em;">
❑ Administer [[aspirin]] for life (I-B)<br>
❑ Initiate/continue [[P2Y12]] receptor inhibitor:<br>
:❑ [[Clopidogrel]] (I-B)<br>'''OR''' <br>
:❑ [[Ticagrelor]] (I-B)<br>'''OR''' <br>
:❑ [[Prasugrel]] (I-B)<br>'''OR''' <br>
❑ Initiate/continue [[GPI]] (if not treated with bivalirudin at the time of PCI):<br>
: High risk patients without adequate clopidogrel pre-treatment (I-A)
: High risk patients with adequate clopidogrel pre-treatment (I-B)
❑ Initiate/Continue anticoagulant therapy:
:❑ Enoxaparin (I-A)
:❑ UFH (I-B)
:❑ Bivalirudin (I-B)
:❑ Fondaparinux (not as a sole agent)</div>
| M03=<div style="float: left; text-align: left; width: 17em; padding:1em;">
❑ Continue [[aspirin]] (I-B)<br>
❑ Discontinue IV [[GP IIb/IIIa]] inhibitors (I-B):<br>
:❑ Discontinue eptifibatide/tirofiban if started before angiography (2 to 4 hours prior to CABG)<br>
:❑ Discontinue abciximab if started before angiography (≥ 12 hours prior to CABG)<br>
❑ Manage the P2Y12 receptor inhibitor therapy as follows:
''If CABG can be delayed'':<br>
:❑ Discontinue clopidogrel if started before angiography (5 days prior to CABG)<br>
:❑ Discontinue ticagrelor if started before angiography (5 days prior to CABG)<br>
:❑ Discontinue prasugrel if started before angiography (7 days prior to CABG)<br>
''If CABG is urgent'':<br>
:❑ Discontinue clopidogrel if started before angiography (up to 24 hours prior to CABG)<br>
:❑ Discontinue ticagrelor if started before angiography (up to 24 hours prior to CABG)<br>
❑ Manage the [[anticoagulation]] therapy <br>
:❑ Continue [[UFH]] (I-B)
:❑ Discontinue [[enoxaparin]] if started before angiography (12-24 hours prior to CABG) and dose with UFH (I-B)<br>
:❑ Discontinue [[fondaparinux]] if started before angiography (24 hours prior to CABG) and dose with UFH (I-B)<br>
:❑ Discontinue [[bivalirudin]] if started before angiography (3 hours prior to CABG) and dose with UFH (I-B)</div>
|M04= <div style="float: left; text-align: left; width: 17em; padding:1em;"> ❑ Continue [[aspirin]] (I-A)<br>
❑ Administer a loading dose of [[P2Y12]] receptor inhibitors ''if not given before angiography'' (I-B)
:❑ [[Clopidogrel]] (300 mg or 600 mg)<br>'''OR''' <br>
:❑ [[Prasugrel]] (60 mg) <br>
❑ Discontinue IV [[GP IIb/IIIa]] inhibitors if started before angiography (I-B)<br>
❑ Manage [[antithrombotic]] therapy:
:❑ Continue IV [[UFH]] for at least 48 hours or until discharge if started before angiography (I-A)<br>
:❑ Continue [[enoxaparin]] for entire hospital stay, up to 8 days if started before angiography (I-A)<br>
:❑ Continue [[fondaparinux]] for entire hospital stay, up to 8 days if started before angiography (I-B)<br>
:❑ Discontinue [[bivalirudin]] or continue at 0.25 mg/kg/hour for up to 72 hours (I-B)</div> }}
{{familytree/end}}
{{familytree/end}}


==Complete Diagnostic Approach==
A complete diagnostic approach should be carried out after a focused initial rapid evaluation is conducted and following initiation of any urgent intervention.<ref name="pmid22809746">{{cite journal| author=Jneid H, Anderson JL, Wright RS, Adams CD, Bridges CR, Casey DE et al.| title=2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non-ST-elevation myocardial infarction (updating the 2007 guideline and replacing the 2011 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. | journal=J Am Coll Cardiol | year= 2012 | volume= 60 | issue= 7 | pages= 645-81 | pmid=22809746 | doi=10.1016/j.jacc.2012.06.004 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22809746  }} </ref>
<span style="font-size:85%"> '''Abbreviations:''' '''CABG:''' [[coronary artery bypass graft]]; '''ECG:''' [[electrocardiogram]]; '''LAD:''' [[LAD|left anterior descending]]; '''LBBB:''' [[left bundle branch block]]; '''MI:''' [[myocardial infarction]]; '''PCI:''' [[percutaneous coronary intervention]]; '''S3:''' [[S3|third heart sound]]; '''S4:''' [[S4|fourth heart sound]]; '''VSD:''' [[ventricular septal defect]] </span>
{{Family tree/start}}
{{familytree  | A01 | | A01=<div style="float: left; text-align: left; width: 28em; padding:1em;"> '''Characterize the symptoms:''' <br>
❑ [[Chest pain]] or [[chest discomfort]] <br>
:❑ Sudden onset
:❑ Sensation of heaviness, tightness, pressure, or squeezing
:❑ Duration> 20 minutes <br>
:❑ Radiation to the left arm, jaw, neck, right arm, back or [[epigastrium]]
:❑ No relief with rest <br>
:❑ Worse with time <br>
:❑ Worse with exertion<br>
❑ [[Dyspnea]] <br>
❑ [[Weakness]] <br>
❑ [[Palpitations]] <br>
❑ [[Nausea]] <br>
❑ [[Vomiting]] <br>
❑ [[Sweating]] <br>
❑ [[Loss of consciousness]]<br>
❑ [[Fatigue]]
</div>}}
{{familytree  | |!| | |}}
{{familytree  | B01 | |  B01=<div style="float: left; text-align: left; width: 35em; padding:1em;"> '''Obtain a detailed history:''' <br>
❑ Age <br>
❑ Baseline [[blood pressure]] <br>
❑ Previous episodes of [[chest pain]] <br>
❑ Previous [[PCI]] or [[CABG]] <br>
❑ Cardiac risk factors<br>
:❑ [[Hypertension]] <br>
:❑ [[Diabetes]] <br>
:❑ [[Hypercholesterolemia]] <br>
:❑ [[Smoking]] <br>
:❑ [[Obesity]] <br>
❑ List of medications <br>
❑ Family history of premature [[coronary artery disease]]
----
'''Identify possible triggers:'''<br>
❑ Physical exertion <br>
❑ Air pollution or fine particulate matter <br>
❑ Antecedant infection <br>
❑ Heavy meal <br>
❑ [[Cocaine]] <br>
❑ [[Marijuana]]</div>}}
{{familytree  | |!| | | }}
{{familytree  | C01 | | C01=<div style="float: left; text-align: left; width: 35em; padding:1em;">'''Examine the patient:''' <br>
'''Vital signs''' <br>
❑ [[Blood pressure]] <br>
:❑ [[Blood pressure]] lower than baseline, suggestive of:
:❑ Discrepancy between arms (suggestive of [[aortic dissection]])
:❑ Narrow [[pulse pressure]] (suggestive of [[heart failure]])
❑ [[Heart rate]] <br>
:❑ [[Tachycardia]] (suggestive of [[heart failure]])
:❑ [[Bradycardia]] (suggestive of [[heart block]] or [[bradyarrhythmias]])
'''Pulses''' <br>
❑  [[Femoral artery|Femoral pulse]] (if a patient is to undergo [[PCI]])<br>
:❑ Strength
:❑ [[Bruits]]
'''Skin''' <br>
❑ [[Xanthelasma]] (suggestive of [[dyslipidemia]]) <br>
❑ [[Xanthoma]] (suggestive of [[dyslipidemia]]) <br>
❑ [[Edema]] (suggestive of [[heart failure]])<br>
❑ [[Cyanosis|Cyanotic]] and cold skin, lips, nail bed (suggestive of [[cardiogenic shock]]) <br>
'''Heart''' <br>
❑ [[Heart sounds]]<br>
:❑ [[S3]] (suggestive of [[heart failure]])
:❑ [[S4]] (associated with conditions that increase the stiffness of the ventricle)
❑ [[Murmurs]]
:❑ [[Aortic regurgitation]]: early diastolic high-pitched sound best heard at the left sternal border (suggestive of [[aortic dissection]] with propagation to the aortic arch)
❑ [[Friction rub|Pericardial friction rub]] (suggestive of [[pericarditis]])
'''Lungs''' <br>
❑ [[Rales]] (suggestive of [[heart failure]]) <br>
</div>}}
{{familytree  | |!| | }}
{{familytree  | E01 | E01= <div style="float: left; width: 28em; text-align: left;">'''Order labs and tests:''' <br>
❑ [[EKG]] <br>
❑ Biomarkers <br>
:❑ Troponin I<br>
:❑ CK-MB <br>
❑ [[Echocardiography]]
❑ [[Creatinine]] <br>
❑ [[Glucose]] <br>
❑ [[Hemoglobin]]<br>
❑ Multislice CT coronary imaging (rule out [[CAD]] as cause of pain in
patients with low to intermediate likelihood of [[CAD]] and when [[troponin]] and [[ECG]] are
inconclusive)<ref>{{Cite web  | last =  | first =  | title = http://eurheartj.oxfordjournals.org/content/32/23/2999.full.pdf | url = http://eurheartj.oxfordjournals.org/content/32/23/2999.full.pdf | publisher =  | date =  | accessdate = }}</ref> <br>
❑ [[MRI]] (integrate imaging of function, perfusion and necrosis)<ref>{{Cite web  | last =  | first =  | title = http://eurheartj.oxfordjournals.org/content/32/23/2999.full.pdf | url = http://eurheartj.oxfordjournals.org/content/32/23/2999.full.pdf | publisher =  | date =  | accessdate = }}</ref>
</div>}}
{{Family tree/end}}


====Management Following Angiography====
==Pre-Discharge Care==
<span style="font-size:85%"> '''Abbreviations:''' '''ACE:''' [[angiotensin converting enzyme]]; '''LVEF:''' [[left ventricular ejection fraction]]; '''PCI:''' [[percutaneous coronary intervention]]; '''PO:''' per os; '''VF:''' [[ventricular fibrillation]]; '''VT:''' [[ventricular tachycardia]] </span>


{{Family tree/start}}
{{Family tree/start}}
{{familytree  | | | | | | | | | | | A01 | | | | | | | | A01= '''Did the patient undergo angiography?'''}}
{{familytree  | A01 | | |A01= <div style="float: left; text-align: left; width: 30em; padding:1em;">'''Administer the following medications in patients without contraindications:'''<br>
{{familytree  | | | | | |,|-|-|-|-|-|^|-|-|-|-|-|-|.| | }}
❑ [[Aspirin]] 81-325 mg (indefinitely) (I-A)<br>
{{familytree  | | | | | B01 | | | | | | | | | | | B02 | B01= Yes| B02= No}}
:''Among patients with either GI intolerance or hypersensitivity to aspirin, administer a loading dose followed by maintenance dose of either clopidogrel 75 mg OD (I-B), OR prasugrel 10 mg OD (only in PCI patients) (I-C), OR ticagrelor 90 mg BID (I-C)'' <br>
{{familytree  | | | | | |!| | | | | | | | | | | | |!| | }}
❑ [[Beta blockers]] <br>
{{familytree  | | | | | C01 | | | | | | | | | | | |!| | C01= <div style="float: left; text-align: left; width: 17em; padding:1em;">'''Does the [[angiography]] show coronary vessel obstruction ?'''</div> }}
<span style="font-size:85%;color:red">Contraindicated in heart failure, prolonged or high degree AV block, reactive airway disease, high risk of cardiogenic shock and low cardiac output state</span> :❑ [[Metoprolol tartrate]]
{{familytree  | | |,|-|-|^|-|-|.| | | | | | | | | |!| | | | }}
::❑ Begin with 25 to 50 mg PO every 6 to 12 hour
{{familytree  | | D01 | | | | D02 | | | | | | | | |!| | | | D01=  '''No'''| D02= '''Yes'''}}
::❑ Then, [[metoprolol tartrate]] twice daily or [[metoprolol succinate]] once daily for 2-3 days
{{familytree  | | |!| | | |,|-|^|-|-|-|-|-|.| | | |!| | | }}
::❑ Titate to 200 mg daily, OR
{{familytree  | | |!| | | E01 | | E02 | | E03 | | |!| | E01=<div style="float: left; text-align: left; width: 17em; padding:1em;">❑ 1 or 2 vessel disease <br> ''[[CABG]] or medical therapy might also be considered'' </div>|E02=<div style="float: left; text-align: left; width: 17em; padding:1em;">❑ Left main coronary artery disease <br>❑ 3 vessel disease <br>❑ 2 vessel disease with proximal left anterior descending artery affection <br>❑ [[Left ventricular dysfunction]] <br> ❑Patient treated from [[diabetes]]</div>| E03= }}
:❑ [[Carvedilol]]
{{familytree  | | |!| | | |!| | | |!| | | |!| | | |!| | | |}}
::Begin with 6.25 mg twice daily
{{familytree  | | L03 | | L01 | | L02 | | L03 | | L04 | | L01= '''[[PCI]]''' <br>
::❑ Titrate to 25 mg twice daily
| L02= '''[[CABG]]''' <BR>
❑ [[Calcium channel blockers]] are used as anti-ischemic or antihypertensive drugs and also in [[atrial fibrillation]] when [[beta blockers]] are contraindicated <br>
| L03= '''Medical treatment'''
<span style="font-size:85%;color:red">Contraindicated in heart failure and left ventricular dysfunction</span> <br>
|L04= }}
❑ [[ACE]] inhibitors and [[ARBs]] may also be considered in selected patients (no enough information)<ref name="www.ncbi.nlm.nih.gov">{{Cite web  | last =  | first =  | title = Therapeutic effects of captopril on ischemia and ... [Am Heart J. 1994] - PubMed - NCBI | url = http://www.ncbi.nlm.nih.gov/pubmed?term=8273728 | publisher =  | date =  | accessdate =  }}</ref>
{{familytree  | | |!| | | |!| | | |!| | | |!| | | |!| | | | }}
<br>
{{familytree  | | M01 | | M02 | | M03 | | M04 | | M05 | | | M01= <div style="float: left; text-align: left; width: 17em; padding:1em;"> Continue [[aspirin]] <br>
<span style="font-size:85%;color:red">Contraindicated in hypotension, renal failure and hyperkalemia</span> <br>
❑ Administer a loading dose of [[P2Y12]] receptor inhibitors (if not given before angiography)
❑ [[Atorvastatin]] 80 mg daily
:❑ [[Clopidogrel]] (600 mg), or <br>
----
:❑ [[Prasugrel]] (60 mg) <br>
'''Administer ONE of the following antiplatelet therapy for a duration of:'''
Discontinue IV [[GP IIb/IIIa]] inhibitors if started <br>
: '''Up to 12 months in medically treated with no stenting  (I-B)'''
❑ Manage [[antithrombotic]] therapy if given before angiography:
: '''Up to 12 months in BMS (I-B)'''
:❑ Continue IV [[UFH]] for 48 hours or until discharge
: '''At least 12 months in DES (I-B)'''
:Continue [[enoxaparin]] for entire hospital stay, up to 8 days
❑ [[Clopidogrel]] 75 mg daily, OR <br>
:❑ Continue [[fondaparinux]] for entire hospital stay, up to 8 days
❑ [[Ticagrelor]] 90 mg twice a day, OR <br>
:❑ Discontinue [[bivalirudin]] or continue, 0.25 mg/kg/hour for up to 72 hours</div> |M02=  <div style="float: left; text-align: left; width: 17em; padding:1em;"> ❑ Administer [[aspirin]] for life <br>
❑ [[Prasugrel]] 10 mg daily '''only for patients who underwent PCI'''<br>
❑ Administer a loading dose of [[P2Y12]] receptor inhibitor (if not initially started)<br>
<br>
:❑ [[Clopidogrel]] 600 mg<br>
 
:❑ [[Ticagrelor]] 180 mg<br>
<span style="font-size:85%;color:red">Consider earlier discontinuation in case bleeding risk exceeds benefit of the antiplatelet therapy (I-C).</span> <br>
:❑ [[Prasugrel]] 60 mg<br>
----
❑ Discontinue anticoagulant therapy following PCI in uncomplicated cases (I-B)</div>
'''Assess the patient for ischemia:'''<br>
| M03=<div style="float: left; text-align: left; width: 17em; padding:1em;">
Perform non invasive testing before discharge for the evaluation of ischemia among patients who did not undergo [[coronary angiography]] and in whom [[coronary angiography]] is not warranted due to the absence of high risk features ([[ACC AHA guidelines classification scheme|Class I, level of evidence B]]) <br>
❑ Continue [[aspirin]] (I-A)<br>
Assess the [[LVEF]] ([[ACC AHA guidelines classification scheme|Class I, level of evidence C]])
Discontinue IV [[GP IIb/IIIa]] inhibitors (4 hours before CABG) (I-B)<br>
</div>}}
❑ Manage the P2Y12 receptor inhibitor therapy as follows ''if CABG can be delayed'' (depending on whether benefits of CABG outweigh the risk of bleeding) (I-B):<br>
:❑ Discontinue clopidogrel (5 days prior to CABG) (I-B)<br>
:❑ Discontinue ticagrelor (5 days prior to CABG) (I-C)<br>
:❑ Discontinue prasugrel (7 days prior to CABG) (I-C)<br>
Manage the [[anticoagulation]] therapy <br>
:Continue [[UFH]] (I-B)
:Discontinue [[enoxaparin]] (12-24 hours prior to CABG) and dose with UFH (I-B)<br>
:❑ Discontinue [[fondaparinux]] (24 hours prior to CABG) and dose with UFH (I-B)<br>
:Discontinue [[bivalirudin]] (3 hours prior to CABG) and dose with UFH (I-B)</div>
|M04=
|M05= }}
{{familytree/end}}
{{familytree/end}}
<span style="font-size:85%"> '''Abbreviations:''' '''ACE:''' [[angiotensin converting enzyme]]; '''ARB:''' [[angiotensin receptor blocker]];</span>
{{Family tree/start}}
{{familytree  | A01 | | A01= <div style="float: left; text-align: left; width: 30em; padding:1em;"> ❑ Prepare a list of all the home medications and educate the patient about compliance
:❑ [[Aspirin]] 81-325 mg (indefinitely)
:❑ [[Antiplatelet drug|Antiplatelet therapy]]
:❑ [[Beta blockers]]
:❑ [[ACE inhibitors]] or [[ARB]] (only in selected patients <ref name="ACE">{{Cite web  | last =  | first =  | title = Therapeutic effects of captopril on ischemia and ... [Am Heart J. 1994] - PubMed - NCBI | url = http://www.ncbi.nlm.nih.gov/pubmed?term=8273728 | publisher =  | date =  | accessdate =  }}</ref>
:❑ [[Atorvastatin]] 80 mg daily
❑ Encourage lifestyle modification <br>
:❑ [[Smoking]] cessation
:❑ Physical activity
:❑ Dietary changes
❑ Ensure the initiation of the management of comorbidities
:❑ [[Obesity]]
:❑ [[Dyslipidemia]]
:❑ [[Hypertension]]
:❑ [[Diabetes]]
:❑ [[Heart failure]]
❑ Educate the patient about the early recognition of symptoms of [[acute coronary syndrome]]
❑ Educate the patient about the use of [[nitroglycerin]] 0.4 mg, sublingually, up to 3 doses every 5 minutes </div> }}
{{Family tree/end}}
==Do's==
* Administer a loading dose followed by a maintenance dose of [[clopidogrel]], [[ticagrelor]] or [[prasugrel]] (if [[PCI]] is planned) as initial treatment instead of [[aspirin]] among patients with gastrointestinal intolerance or hypersensitivity reaction to [[aspirin]].
* Administer sublingual [[nitroglycerin]] in patients with ischemic [[chest pain]]; however, administer IV [[nitroglycerin]] among patients with persistent [[chest pain]] after three sublingual [[nitroglycerin]].<ref name="pmid6402912">{{cite journal| author=Kaplan K, Davison R, Parker M, Przybylek J, Teagarden JR, Lesch M| title=Intravenous nitroglycerin for the treatment of angina at rest unresponsive to standard nitrate therapy. | journal=Am J Cardiol | year= 1983 | volume= 51 | issue= 5 | pages= 694-8 | pmid=6402912 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6402912  }} </ref>
*Discontinue [[NSAID]] drugs immediately. <ref name="pmid21224324">{{cite journal| author=Trelle S, Reichenbach S, Wandel S, Hildebrand P, Tschannen B, Villiger PM et al.| title=Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. | journal=BMJ | year= 2011 | volume= 342 | issue=  | pages= c7086 | pmid=21224324 | doi=10.1136/bmj.c7086 | pmc=PMC3019238 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21224324  }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21460398 Review in: Evid Based Med. 2011 Oct;16(5):142-3] </ref>  <ref name="pmid23726390">{{cite journal| author=Coxib and traditional NSAID Trialists' (CNT) Collaboration. Bhala N, Emberson J, Merhi A, Abramson S, Arber N et al.| title=Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. | journal=Lancet | year= 2013 | volume= 382 | issue= 9894 | pages= 769-79 | pmid=23726390 | doi=10.1016/S0140-6736(13)60900-9 | pmc=PMC3778977 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23726390  }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24126661 Review in: Ann Intern Med. 2013 Oct 15;159(8):JC12] </ref>
* If fondaparinux is chosen to be administered ad the anticoagulant therapy during PCI, co-administer another antocoagulant with factor IIa activity such as UFH.
==Don'ts==
* Do not administer IV [[GP IIb/IIIa inhibitors]] to patients with low risk of ischemic events or at high risk of [[bleeding]] and who are already on [[aspirin]] and P2Y12 receptor inhibitors therapy.
* Do not administer [[prasugrel]] among patients with prior history of [[strokes]] or [[TIAs]].
* Do not administer IV [[beta-blockers]] among hemodynamically unstable patients.
* Do not administer a complete dose of [[prasugrel]] among patients under 60kg (132lbs) due to high exposure to the active metabolite.  They should receive half the dose of [[prasugrel]] although there is no evidence that half the dose is as effective as a complete dose.
* Do not administer fibrinolytic therapy to patients with [[unstable angina]].<ref name="pmid7475596">{{cite journal| author=Anderson HV| title=Intravenous thrombolysis in refractory unstable angina pectoris. | journal=Lancet | year= 1995 | volume= 346 | issue= 8983 | pages= 1113-4 | pmid=7475596 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7475596  }} </ref>
*Do not administer [[abciximab]] for patients not scheduled for [[PCI]]. <ref name="pmid22809746">{{cite journal| author=Jneid H, Anderson JL, Wright RS, Adams CD, Bridges CR, Casey DE et al.| title=2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non-ST-elevation myocardial infarction (updating the 2007 guideline and replacing the 2011 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. | journal=J Am Coll Cardiol | year= 2012 | volume= 60 | issue= 7 | pages= 645-81 | pmid=22809746 | doi=10.1016/j.jacc.2012.06.004 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22809746  }} </ref>
* Do not administer 2 P2Y12 receptor inhibitors, even in the presence of hypersensitivity or GI interoperability to aspirin.
==References==
{{reflist|2}}
[[Category:Emergency medicine]]
[[Category:Medicine]]
[[Category:Resident survival guide]]
[[Category:Cardiology]]
{{WikiDoc Help Menu}}
{{WikiDoc Sources}}
</div>

Latest revision as of 21:09, 15 April 2015

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Andrea Tamayo Soto [2]; Rim Halaby, M.D. [3]

Unstable angina/ NSTEMI Resident Survival Guide Microchapters
Overview
Causes
FIRE
Diagnosis
Treatment
Management Following Angiography
Pre-Discharge Care
Long Term Management
Do's
Don'ts

Overview

Unstable angina and non ST elevation myocardial infarction (NSTEMI) belong to two different ends of the spectrum of acute coronary syndrome. These conditions have a similar clinical presentation characterized by an acute onset of chest pain that starts on minimal exertion, rest or sleep, lasts at least 20 minutes (but usually less that half an hour) and, is not relieved by medications or rest. NSTEMI is differentiated from unstable angina by the presence of elevated cardiac biomarkers secondary to myocardial injury. Unstabel angina and NSTEMI might not be differentiated early following the occurrence of symptoms because cardiac biomarkers may require a few hours to rise.

Causes

Life Threatening Causes

Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated. Unstable angina and NSTEMI are life-threatening conditions and must be treated as such irrespective of the causes.

Common Causes

Myocardial Infarction

For a complete list of causes, click here for unstable angina and here for NSTEMI.

FIRE: Focused Initial Rapid Evaluation

A Focused Initial Rapid Evaluation (FIRE) should be performed to identify patients in need of immediate intervention based on the 2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non-ST-elevation myocardial infarction.[1] An invasive strategy is defined as diagnostic angiography with the intention of revascularization.

Boxes in the red color signify that an urgent management is needed.

 
 
 
Identify cardinal findings of unstable angina/ NSTEMI :

Chest pain or chest discomfort

❑ Sudden onset
❑ Sensation of heaviness, tightness, pressure, or squeezing
❑ Duration> 20 minutes (but usually less than half an hour)
❑ Radiation to the left arm, jaw, neck, right arm, back or epigastrium
❑ No relief with medications
❑ No relief with rest
❑ Worse with time
❑ Worse with exertion
❑ Associated symptoms of palpitations, nausea, vomiting, sweating, dyspnea, and lightheadedness

Characteristic ECG changes consistent with unstable angina/ NSTEMI

❑ No changes
❑ Non specific ST / T wave changes
❑ Flipped or inverted T waves
❑ ST depression (carries the poorest prognosis)
Increase in >99th percentile of upper limit of normal of troponin and / or CK MB, which is consistent with NSTEMI
 
 
 
 
 
 
 
 
 
 
 
 
 
Rule out life threatening alternative diagnoses:

Aortic dissection
(suggestive findings: back pain, interscapular pain, aortic regurgitation, pulsus paradoxus, blood pressure discrepancy between the arms)
Pulmonary embolism
(suggestive findings: acute onset of dyspnea, tachypnea, hemoptysis, previous DVT)
Cardiac tamponade
(suggestive findings: hypotension, jugular venous distention, muffled heart sounds, pulsus paradoxus)
Tension pneumothorax
(suggestive findings: sudden dyspnea, tachycardia, chest trauma, unilateral absence of breath sound)

Esophageal rupture
(suggestive findings: vomiting, subcutaneous emphysema)
 
 
 
 
 
 
 
 
 
 
 
 
Begin initial treatment:

❑ Administer 162 to 325 mg of non enteric aspirin,orally, crushed or chewed (I-A)

Among patients with either GI intolerance or hypersensitivity to aspirin, administer a loading dose (75 mg) followed by maintenance dose of clopidogrel (I-B)

❑ Administer 2-4 L/min oxygen via nasal cannula when saturation <90% (I-C)

Caution in COPD patients: maintain an oxygen saturation between 88% and 92%.

❑ Administer nitroglycerin

❑ Administer sublingual nitroglycerin (0.3 to 0.4 mg, every 5 minutes for a total of 3 doses) then assess for further need to IV nitroglycerin (I-C)
❑ Administer IV nitroglyerin in case of persistent chest pain despite PO nitroglycerin, heart failure, or hypertenion (I-B): 10 mcg/min, increase by 10 mcg/min every 3 to 5 minutes until symptom relief; in case no response at 20 mcg/min, can increase by 10 mcg/min and then by 20 mcg/min

Contraindicated in suspected right ventricular MI, recent use of phosphodiesterase inhibitors, decreased blood pressure 30 mmHg below baseline
❑ Administer beta-blockers (unless contraindicated) and titrate to the heart rate and blood pressure (I-A)

PO in general, IV if patient has hypertension or ongoing pain
Beta blocker is contraindicated in heart failure and high risk of cardiogenic shock.
Metoprolol:
PO: 25 to 50 mg every 6 hours
IV: 5 mg every 5 min, up to 3 doses, then 25 to 50 mg orally every 6 hours
Carvedilol IV, 25 mg, two times a day

Contraindicated in heart failure, bradycardia, hypotension (SBP<90 mmHg), second or third degree AV block, reactive airway disease, high risk of cardiogenic shock and low cardiac output state
❑ Administer IV morphine if persistent symptoms (IIb-B) or pulmonary edema

❑ Initial dose 4-8 mg
❑ 2-8 mg every 5 to 15 minutes, as needed

❑ Administer 80 mg atorvastatin (I-A)
❑ Monitor with a 12-lead ECG all the time

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
TRIAGE FOR IMMEDIATE INTERVENTION
Does the patient have ANY of the following indications that require immediate angiography and revascularization ?

❑ Hemodynamic instability or cardiogenic shock, OR
❑ Severe left ventricular dysfunction or heart failure, OR
❑ Recurrent or persistent rest angina despite intensive medical therapy, OR
❑ New or worsening mitral regurgitation or new VSD, OR
❑ Sustained VT or VF, OR

❑ Prior PCI within past 6 months or CABG
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
YES
 
 
 
NO
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Does the patient have no ECG changes AND no rise in cardiac biomarkers > 99th percentile of ULN?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Yes. The patient has no ECG changes AND no rise in cardiac biomarkers > 99th percentile of ULN.
 
No. The patient has either positive ECG changes, OR rise in cardiac biomarkers, OR both.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Repeat ECG and biomarkers within next 3 hours and 6 hours

Does the patient still have no ECG changes AND no rise in cardiac biomarkers?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Yes. The patient has no ECG changes AND no rise in cardiac biomarkers.
 
No. The patient has either positive ECG changes, OR rise in cardiac biomarkers, OR both.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
TRIAGE FOR INITIAL CONSERVATIVE OR INVASIVE THERAPY
Calculate the risk of future adverse clinical outcomes:

Thrombolysis in Myocardial Infarction (TIMI) risk score, OR

GRACE score
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Intermediate or high risk
 
Low risk
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
INITIAL INVASIVE THERAPY (IMMEDIATELY)
 
INITIAL INVASIVE THERAPY (4 to 48 hours)
 
INITIAL CONSERVATIVE THERAPY
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Initiate ONE of the following anticoagulant therapy (I-A)

❑ Enoxaparin (I-A)

❑ SC 1 mg/kg every 12 hours if CrCL≥ 30 mL/min
❑ SC 1 mg/kg every 12 hours if CrCL< 30 mL/min
❑ Initial IV 30 mg loading dose in selected patients

OR
❑ IV Unfractionated heparin (and adjust dose for apTT) for 48 hours or until PCI is perfomed (I-B)

❑ Initial loading dose 60 IU/kg (max 40,000 IU)
❑ Initial infusion 12 IU/kg/h (max 10,000 IU)
OR

Bivalirudin (I-B)

❑ Loading dose 0.1-mg/kg IV bolus, then 0.25–mg/kg/h infusion


OR
❑ Fondaparinux , SC 2.5 mg daily (I-B)

PLUS

Administer ONE of the following antiplatelet agents (before OR at the time of PCI) (I-A)
❑ Loading dose of P2Y12 receptor inhibitors

Clopidogrel (I-B if before PCI, I-A if at time of PCI)
Loading dose: 300 mg or 600 mg
Maintenance dose: 75 mg OD


OR

Ticagrelor (I-B)
Loading dose: 180 mg
Maintenance dose: 90 mg BID


OR

❑ Prasugrel ONLY AT THE TIME OF PCI, AND NOT PRE-PCI (I-B)
Loading dose: 60 mg
Maintenance dose: 10 mg OD

Prasugrel is contraindicated in case of prior history of strokes or TIAs, active pathological bleeding, age ≥75 years, when urgent coronary artery bypass graft surgery (CABG) is likely, body weight <60 kg, propensity to bleed, concomitant use of medications that increase the risk of bleeding

Consider adding IV GP IIb/IIIa inhibitors in case of high risk patients (IIb-B)
Eptifibatide

❑ Loading dose 180 mcg/kg IV bolus followed by another bolus after 10 minutes
❑ Maintenance dose 2 mcg/kg/min
OR

Tirofiban

❑ Loading dose 25 mcg/kg
❑ Maintenance dose 0.15 mcg/kg/min
 
 
 
Initiate ONE of the following anticoagulant therapy (I-A)

❑ Enoxaparin (I-A)
OR
❑ UFH (I-B)
OR
❑ Fondaparinux (I-B)



PLUS

Administer ONE of the following antiplatelet agents (I-B):
P2Y12 receptor inhibitors

Clopidogrel
❑ Loading dose (300 mg or 600 mg)
❑ Maintenance dose (75 mg)
OR
Ticagrelor
❑ Loading dose (180 mg)
❑ Maintenance dose (90 mg twice daily)
OR
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
TRIAGE FOR NEED OF INVASIVE THERAPY
Does the patient experience ANY of the following?

❑ Recurrence of symptoms, OR
Heart failure, OR
❑ Serious arrhythmia, OR

❑ Subsequent ischemia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
YES
 
NO
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PROCEED TO INVASIVE THERAPY (I-A)

Administer ONE of the following antiplatelet agents if not already administered (I-A):

The antiplatelet should be administered upstream (I-C)

P2Y12 receptor inhibitors

Clopidogrel (I-B)
❑ Loading dose (300 mg or 600 mg)
❑ Maintenance dose (75 mg)
OR
Ticagrelor (I-B)
❑ Loading dose (180 mg)
❑ Maintenance dose (90 mg twice daily)
OR

❑ IV GP IIb/IIIa inhibitors (I-A)

Eptifibatide
❑ Loading dose 180 mcg/kg IV bolus followed by another bolus after 10 minutes
❑ Maintenance dose 2 mcg/kg/min
OR
Tirofiban
❑ Loading dose 25 mcg/kg
❑ Maintenance dose 0.15 mcg/kg/min
 
TRIAGE PATIENTS BY RISK ON STRESS TEST
❑ Perform a stress test (I-B)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
High risk on stress test
 
Low risk on stress test OR did not undergo stress test
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
INVASIVE THERAPY
❑ Perform diagnostic angiography (I-A)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Continue aspirin for life (I-A)
❑ Continue P2Y12 receptor inhibitors up to 12 months (I-B)
Clopidogrel (75 mg once a day)
OR
Ticagrelor (90 mg twice a day)

❑ Discontinue GP IIb/IIIa inhibitors if administered earlier (I-A)
❑ Continue antithrombotic therapy:

UFH for 48 hours (I-A)
OR
Enoxaparin for duration of hospitalization (up to 8 days) (I-A)
OR
Fondaparinux for duration of hospitalization (up to 8 days) (I-B)
❑ Measure LVEF (I-B)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
TRIAGE FOR SUBSEQUENT THERAPY PLAN FOLLOWING ANGIOGRAPHY
Does the angiography show coronary vessel obstruction ?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No
 
 
 
Yes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ 1 or 2 vessel disease
CABG or medical therapy might also be considered
 
❑ Left main coronary artery disease
❑ 3 vessel disease
❑ 2 vessel disease with proximal left anterior descending artery affection
Left ventricular dysfunction
❑Patient treated from diabetes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical treatment
 
PCI
 
CABG
 
Medical treatment
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

❑ Administer aspirin indefinitely
❑ Administer additional antiplatelet therapy at the discretion of the physician (I-C)

❑ Administer anticoagulant therapy at the discretion of the physician (I-C)
 

❑ Administer aspirin for life (I-B)
❑ Initiate/continue P2Y12 receptor inhibitor:

Clopidogrel (I-B)
OR
Ticagrelor (I-B)
OR
Prasugrel (I-B)
OR

❑ Initiate/continue GPI (if not treated with bivalirudin at the time of PCI):

High risk patients without adequate clopidogrel pre-treatment (I-A)
High risk patients with adequate clopidogrel pre-treatment (I-B)

❑ Initiate/Continue anticoagulant therapy:

❑ Enoxaparin (I-A)
❑ UFH (I-B)
❑ Bivalirudin (I-B)
❑ Fondaparinux (not as a sole agent)
 

❑ Continue aspirin (I-B)
❑ Discontinue IV GP IIb/IIIa inhibitors (I-B):

❑ Discontinue eptifibatide/tirofiban if started before angiography (2 to 4 hours prior to CABG)
❑ Discontinue abciximab if started before angiography (≥ 12 hours prior to CABG)

❑ Manage the P2Y12 receptor inhibitor therapy as follows: If CABG can be delayed:

❑ Discontinue clopidogrel if started before angiography (5 days prior to CABG)
❑ Discontinue ticagrelor if started before angiography (5 days prior to CABG)
❑ Discontinue prasugrel if started before angiography (7 days prior to CABG)

If CABG is urgent:

❑ Discontinue clopidogrel if started before angiography (up to 24 hours prior to CABG)
❑ Discontinue ticagrelor if started before angiography (up to 24 hours prior to CABG)

❑ Manage the anticoagulation therapy

❑ Continue UFH (I-B)
❑ Discontinue enoxaparin if started before angiography (12-24 hours prior to CABG) and dose with UFH (I-B)
❑ Discontinue fondaparinux if started before angiography (24 hours prior to CABG) and dose with UFH (I-B)
❑ Discontinue bivalirudin if started before angiography (3 hours prior to CABG) and dose with UFH (I-B)
 
❑ Continue aspirin (I-A)

❑ Administer a loading dose of P2Y12 receptor inhibitors if not given before angiography (I-B)

Clopidogrel (300 mg or 600 mg)
OR
Prasugrel (60 mg)

❑ Discontinue IV GP IIb/IIIa inhibitors if started before angiography (I-B)
❑ Manage antithrombotic therapy:

❑ Continue IV UFH for at least 48 hours or until discharge if started before angiography (I-A)
❑ Continue enoxaparin for entire hospital stay, up to 8 days if started before angiography (I-A)
❑ Continue fondaparinux for entire hospital stay, up to 8 days if started before angiography (I-B)
❑ Discontinue bivalirudin or continue at 0.25 mg/kg/hour for up to 72 hours (I-B)
 

Complete Diagnostic Approach

A complete diagnostic approach should be carried out after a focused initial rapid evaluation is conducted and following initiation of any urgent intervention.[1]

Abbreviations: CABG: coronary artery bypass graft; ECG: electrocardiogram; LAD: left anterior descending; LBBB: left bundle branch block; MI: myocardial infarction; PCI: percutaneous coronary intervention; S3: third heart sound; S4: fourth heart sound; VSD: ventricular septal defect

Characterize the symptoms:

Chest pain or chest discomfort

❑ Sudden onset
❑ Sensation of heaviness, tightness, pressure, or squeezing
❑ Duration> 20 minutes
❑ Radiation to the left arm, jaw, neck, right arm, back or epigastrium
❑ No relief with rest
❑ Worse with time
❑ Worse with exertion

Dyspnea
Weakness
Palpitations
Nausea
Vomiting
Sweating
Loss of consciousness
Fatigue

 
 
 
 
 
 
Obtain a detailed history:

❑ Age
❑ Baseline blood pressure
❑ Previous episodes of chest pain
❑ Previous PCI or CABG
❑ Cardiac risk factors

Hypertension
Diabetes
Hypercholesterolemia
Smoking
Obesity

❑ List of medications
❑ Family history of premature coronary artery disease


Identify possible triggers:
❑ Physical exertion
❑ Air pollution or fine particulate matter
❑ Antecedant infection
❑ Heavy meal
Cocaine

Marijuana
 
 
 
 
 
 
 
Examine the patient:

Vital signs
Blood pressure

Blood pressure lower than baseline, suggestive of:
❑ Discrepancy between arms (suggestive of aortic dissection)
❑ Narrow pulse pressure (suggestive of heart failure)

Heart rate

Tachycardia (suggestive of heart failure)
Bradycardia (suggestive of heart block or bradyarrhythmias)

Pulses
Femoral pulse (if a patient is to undergo PCI)

❑ Strength
Bruits

Skin
Xanthelasma (suggestive of dyslipidemia)
Xanthoma (suggestive of dyslipidemia)
Edema (suggestive of heart failure)
Cyanotic and cold skin, lips, nail bed (suggestive of cardiogenic shock)

Heart
Heart sounds

S3 (suggestive of heart failure)
S4 (associated with conditions that increase the stiffness of the ventricle)

Murmurs

Aortic regurgitation: early diastolic high-pitched sound best heard at the left sternal border (suggestive of aortic dissection with propagation to the aortic arch)

Pericardial friction rub (suggestive of pericarditis)

Lungs
Rales (suggestive of heart failure)

 
 
 
 
 
 
Order labs and tests:

EKG
❑ Biomarkers

❑ Troponin I
❑ CK-MB

EchocardiographyCreatinine
Glucose
Hemoglobin
❑ Multislice CT coronary imaging (rule out CAD as cause of pain in patients with low to intermediate likelihood of CAD and when troponin and ECG are inconclusive)[2]
MRI (integrate imaging of function, perfusion and necrosis)[3]

Pre-Discharge Care

Abbreviations: ACE: angiotensin converting enzyme; LVEF: left ventricular ejection fraction; PCI: percutaneous coronary intervention; PO: per os; VF: ventricular fibrillation; VT: ventricular tachycardia

Administer the following medications in patients without contraindications:

Aspirin 81-325 mg (indefinitely) (I-A)

Among patients with either GI intolerance or hypersensitivity to aspirin, administer a loading dose followed by maintenance dose of either clopidogrel 75 mg OD (I-B), OR prasugrel 10 mg OD (only in PCI patients) (I-C), OR ticagrelor 90 mg BID (I-C)

Beta blockers
Contraindicated in heart failure, prolonged or high degree AV block, reactive airway disease, high risk of cardiogenic shock and low cardiac output state :❑ Metoprolol tartrate

❑ Begin with 25 to 50 mg PO every 6 to 12 hour
❑ Then, metoprolol tartrate twice daily or metoprolol succinate once daily for 2-3 days
❑ Titate to 200 mg daily, OR
Carvedilol
❑ Begin with 6.25 mg twice daily
❑ Titrate to 25 mg twice daily

Calcium channel blockers are used as anti-ischemic or antihypertensive drugs and also in atrial fibrillation when beta blockers are contraindicated
Contraindicated in heart failure and left ventricular dysfunction
ACE inhibitors and ARBs may also be considered in selected patients (no enough information)[4]
Contraindicated in hypotension, renal failure and hyperkalemia
Atorvastatin 80 mg daily


Administer ONE of the following antiplatelet therapy for a duration of:

Up to 12 months in medically treated with no stenting (I-B)
Up to 12 months in BMS (I-B)
At least 12 months in DES (I-B)

Clopidogrel 75 mg daily, OR
Ticagrelor 90 mg twice a day, OR
Prasugrel 10 mg daily only for patients who underwent PCI

Consider earlier discontinuation in case bleeding risk exceeds benefit of the antiplatelet therapy (I-C).


Assess the patient for ischemia:
❑ Perform non invasive testing before discharge for the evaluation of ischemia among patients who did not undergo coronary angiography and in whom coronary angiography is not warranted due to the absence of high risk features (Class I, level of evidence B)
❑ Assess the LVEF (Class I, level of evidence C)

 
 


Abbreviations: ACE: angiotensin converting enzyme; ARB: angiotensin receptor blocker;

❑ Prepare a list of all the home medications and educate the patient about compliance
Aspirin 81-325 mg (indefinitely)
Antiplatelet therapy
Beta blockers
ACE inhibitors or ARB (only in selected patients [5]
Atorvastatin 80 mg daily

❑ Encourage lifestyle modification

Smoking cessation
❑ Physical activity
❑ Dietary changes

❑ Ensure the initiation of the management of comorbidities

Obesity
Dyslipidemia
Hypertension
Diabetes
Heart failure

❑ Educate the patient about the early recognition of symptoms of acute coronary syndrome

❑ Educate the patient about the use of nitroglycerin 0.4 mg, sublingually, up to 3 doses every 5 minutes
 

Do's

  • Administer a loading dose followed by a maintenance dose of clopidogrel, ticagrelor or prasugrel (if PCI is planned) as initial treatment instead of aspirin among patients with gastrointestinal intolerance or hypersensitivity reaction to aspirin.
  • If fondaparinux is chosen to be administered ad the anticoagulant therapy during PCI, co-administer another antocoagulant with factor IIa activity such as UFH.

Don'ts

  • Do not administer IV GP IIb/IIIa inhibitors to patients with low risk of ischemic events or at high risk of bleeding and who are already on aspirin and P2Y12 receptor inhibitors therapy.
  • Do not administer IV beta-blockers among hemodynamically unstable patients.
  • Do not administer a complete dose of prasugrel among patients under 60kg (132lbs) due to high exposure to the active metabolite. They should receive half the dose of prasugrel although there is no evidence that half the dose is as effective as a complete dose.
  • Do not administer 2 P2Y12 receptor inhibitors, even in the presence of hypersensitivity or GI interoperability to aspirin.

References

  1. 1.0 1.1 1.2 Jneid H, Anderson JL, Wright RS, Adams CD, Bridges CR, Casey DE; et al. (2012). "2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non-ST-elevation myocardial infarction (updating the 2007 guideline and replacing the 2011 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines". J Am Coll Cardiol. 60 (7): 645–81. doi:10.1016/j.jacc.2012.06.004. PMID 22809746.
  2. "http://eurheartj.oxfordjournals.org/content/32/23/2999.full.pdf" (PDF). External link in |title= (help)
  3. "http://eurheartj.oxfordjournals.org/content/32/23/2999.full.pdf" (PDF). External link in |title= (help)
  4. "Therapeutic effects of captopril on ischemia and ... [Am Heart J. 1994] - PubMed - NCBI".
  5. "Therapeutic effects of captopril on ischemia and ... [Am Heart J. 1994] - PubMed - NCBI".
  6. Kaplan K, Davison R, Parker M, Przybylek J, Teagarden JR, Lesch M (1983). "Intravenous nitroglycerin for the treatment of angina at rest unresponsive to standard nitrate therapy". Am J Cardiol. 51 (5): 694–8. PMID 6402912.
  7. Trelle S, Reichenbach S, Wandel S, Hildebrand P, Tschannen B, Villiger PM; et al. (2011). "Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis". BMJ. 342: c7086. doi:10.1136/bmj.c7086. PMC 3019238. PMID 21224324. Review in: Evid Based Med. 2011 Oct;16(5):142-3
  8. Coxib and traditional NSAID Trialists' (CNT) Collaboration. Bhala N, Emberson J, Merhi A, Abramson S, Arber N; et al. (2013). "Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials". Lancet. 382 (9894): 769–79. doi:10.1016/S0140-6736(13)60900-9. PMC 3778977. PMID 23726390. Review in: Ann Intern Med. 2013 Oct 15;159(8):JC12
  9. Anderson HV (1995). "Intravenous thrombolysis in refractory unstable angina pectoris". Lancet. 346 (8983): 1113–4. PMID 7475596.


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