Unstable angina/ NSTEMI resident survival guide

Jump to navigation Jump to search

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 is an unexpected chest pain that starts on minimal exertion, rest or sleep, lasts at least 20 minutes up to half an hour and is not relieved by medications or rest. Unstable angina and non ST elevation myocardial infarction (NSTEMI) belong to two different ends of the spectrum of acute coronary syndrome. Unstable angina is differentiated from NSTEMI by the absence of elevated cardiac biomarkers.

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

FIRE: Focused Initial Rapid Evaluation

A Focused Initial Rapid Evaluation (FIRE) should be performed to identify patients in need of immediate intervention.

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
❑ 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 and sweating

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 troponin and / or CK MB
 
 
 
 
 
 
 
 
 
 
 
 
 
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 - 325 mg of non enteric aspirin
❑ Orally, crushed or chewed, OR
❑ Intravenously

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

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

❑ Administer beta-blockers (unless contraindicated) and titrate to the heart rate and blood pressure
Contraindicated in heart failure , prolonged or high degree AV block , reactive airway disease , high risk of cardiogenic shock and low cardiac output state

Metoprolol IV, 5 mg every 5 min, up to 3 doses
Carvedilol IV, 25 mg, two times a day

❑ Administer sublingual nitroglycerin 0.4 mg every 5 minutes for a total of 3 doses
Contraindicated in suspected right ventricular MI , recent use of phosphodiesterase inhibitors , decreased blood pressure 30 mmHg below baseline
❑ Administer IV morphine if needed

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

❑ Administer 80 mg atorvastatin
❑ Monitor with a 12-lead ECG all the time

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Does the patient have any of the following indications that require immediate angiography and revascularization ?

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

❑ Prior PCI within past 6 months or CABG
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
YES
 
 
 
NO
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Proceed to angiography
 
Low risk
Initial conservative strategy
 
High risk
Initial invasive strategy
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Administer ONE of the following antiplatelet agents (before or at the time of PCI):
P2Y12 receptor inhibitors

Clopidogrel 600 mg
Ticagrelor 180 mg
Prasugrel 60 mg

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
❑ IV GP IIb/IIIa inhibitors

Abciximab
❑ Loading dose 0.25 mg/kg IV bolus
❑ Maintenance dose 0.125 mg/kg/min
Eptifibatide
❑ Loading dose 180 mcg/kg IV bolus
❑ Another 180 mcg/kg IV bolus after 10 minutes
❑ Maintenance dose 2 mcg/kg/min
❑ Decrease infusion by 50% if creatinine clearance <50 mL/min
❑ Avoid in hemodialysis patients
Tirofiban
❑ Loading dose 25 mcg/kg
❑ Maintenance dose 0.15 mcg/kg/min
❑ Decrease infusion by 50% if creatinine clearance <30 mL/min

Administer ONE of the following anticoagulant therapy:
Unfractionated heparin

If GP IIb/IIIa receptor antagonist is planned
❑ 50- to 70-U/kg IV bolus
If no GP IIb/IIIa receptor antagonist is planned
❑ 70- to 100-U/kg bolus

Bivalirudin

❑ 0.75-mg/kg IV bolus, then 1.75–mg/kg/h infusion
❑ Additional bolus of 0.3 mg/kg if needed
❑ Decrease infusion to 1 mg/kg/h when creatinine clearance <30 mL/min
 
Administer one of the following antiplatelet agents:

Clopidogrel

❑ Loading dose (300 mg)
❑ Maintenance dose for up to 12 months (75 mg)

Ticagrelor

❑ Loading dose (180 mg)
❑ Maintenance dose for up to 12 months (90 mg twice daily)
 
Administer one of the following antiplatelet agents:

Before PCI
P2Y12 receptor inhibitors

Clopidogrel (600 mg), or
Ticagrelor (180 mg), or

❑ IV GP IIb/IIIa inhibitors

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

At the time of PCI
P2Y12 receptor inhibitors

Clopidogrel (600 mg), or
Ticagrelor (180 mg), or
❑ Prasugrel (60 mg)

❑ IV GP IIb/IIIa inhibitors

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
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Consider urgent CABG if the coronary anatomy is not amenable to PCI and one of the following:[1]
❑ Patients with left main or left main equivalent disease
❑ Patients with three or two vessel disease involving the left anterior descending artery with left ventricular dysfunction
❑ Diabetic patients
 
 
❑ Perform an angiography
 

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.[2]

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)[3]
MRI (integrate imaging of function, perfusion and necrosis)[4]

Treatment

Shown below is an algorithm summarizing the management of unstable angina and NSTEMI based on the 2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non-ST-elevation myocardial infarction.[2]

 
 
 
 
 
 
Initial Treatment
❑ Administer 162 - 325 mg of aspirin

❑ Administer oxygen when saturation <90%

❑ 2-4 L/min via nasal cannula

❑ Administer beta-blockers (unless contraindicated)

Metoprolol IV, 5 mg every 5 min, up to 3 doses
Carvedilol IV, 6,25 mg, two times a day (titrate to heart rate)

❑ Administer sublingual nitroglycerin 0.4 mg every 5 minutes for a total of 3 doses
❑ Administer IV morphine if needed

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

❑ Administer 80 mg atorvastatin
❑ Administer antithrombotic treatment

Fondaparinux, or
UFH in case of renal failure
❑ Monitor with a 12-lead EKG all the time
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Determine the risk of adverse coronary event:

TIMI Score, or
HEART Risk Score, or

GRACE Risk Score
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Low risk
Initial conservative strategy
 
 
 
 
 
High risk
Initial invasive strategy
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Administer one of the following antiplatelet agents:

Clopidogrel

❑ Loading dose (300 mg)
❑ Maintenance dose for up to 12 months (75 mg)

Ticagrelor

❑ Loading dose (180 mg)
❑ Maintenance dose for up to 12 months (90 mg twice daily)
 
 
 
 
 

Administer one of the following antiplatelet agents:
Before PCI
P2Y12 receptor inhibitors

Clopidogrel (600 mg), or
Ticagrelor (180 mg), or

❑ IV GP IIb/IIIa inhibitors

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

At the time of PCI
P2Y12 receptor inhibitors

Clopidogrel (600 mg), or
Ticagrelor (180 mg), or
❑ Prasugrel (60 mg)

❑ IV GP IIb/IIIa inhibitors

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
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Recurrent or worsening symptoms?
 
 
 
 
 
❑ Perform an angiography
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Recurrence of symptoms
Heart failure
❑ Serious arrhythmia
❑ Subsequent ischemia
 
No recurrent symptoms
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Perform an angiography

Administer upstream antiplatelet agent:
P2Y12 receptor inhibitors

Clopidogrel
❑ Loading dose (600 mg)
❑ Maintenance dose (75 mg), or
Ticagrelor
❑ Loading dose (180 mg)
❑ Maintenance dose (90 mg twice daily), or

❑ IV GP IIb/IIIa inhibitors

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
 
❑ Perform a stress test
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Low Risk
 
High Risk
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Perform an angiography
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Continue aspirin for life
❑ Continue P2Y12 receptor inhibitors up to 12 months
Clopidogrel (75 mg once a day), or
Ticagrelor (90 mg twice a day)

❑ Discontinue GP IIb/IIIa inhibitors
❑ Continue antithrombotic therapy:

UFH for 48 hours, or
Enoxaparin for up to 8 days, or
Fondaparinux for up to 8 days
 
 
 
 
 
 


Management 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
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Continue aspirin

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

Clopidogrel (600 mg), or
Prasugrel (60 mg)

❑ Discontinue IV GP IIb/IIIa inhibitors if started
❑ Manage antithrombotic therapy if given before angiography:

❑ Continue IV UFH for 48 hours or until discharge
❑ Continue enoxaparin for entire hospital stay, up to 8 days
❑ Continue fondaparinux for entire hospital stay, up to 8 days
❑ Discontinue bivalirudin or continue, 0.25 mg/kg/hour for up to 72 hours
 
❑ Administer aspirin for life

❑ Administer a loading dose of P2Y12 receptor inhibitor (if not initially started)

Clopidogrel 600 mg
Ticagrelor 180 mg
Prasugrel 60 mg
❑ Discontinue anticoagulant in uncomplicated cases
 
 
 
 
 

❑ Continue aspirin
❑ Discontinue IV GP IIb/IIIa inhibitors (4 hours before CABG)
❑ Manage the P2Y12 receptor inhibitor therapy (if CABG can be delayed)

❑ Discontinue clopidogrel (5 days prior to CABG)
❑ Discontinue ticagrelor (5 days prior to CABG)
❑ Discontinue prasugrel (7 days prior to CABG)

❑ Manage the antithrombotic therapy

❑ Continue UFH
❑ Discontinue enoxaparin (12-24 hours prior to CABG)
❑ Discontinue fondaparinux (24 hours prior to CABG)
❑ Discontinue bivalirudin (3 hours prior to CABG)
 
 
 
 

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)
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 the management
Contraindicated in hypotension, renal failure and hyperkalemia
Atorvastatin 80 mg daily


Administer antiplatelet therapy

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


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)

 
 

Long Term Management

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
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
 


Thrombolysis in Myocardial Infarction (TIMI) Risk Score

Shown below is a table summarizing the TIMI scoring system. The risk of subsequent death, myocardial Infarction or need for revascularization within two weeks from the initial presentation is 4.7%, 8.3%, 13.2%, 19.9%, 26.2%, 40.9% for risk scores of 0-1, 2, 3, 4, 5, 6 and 7 respectively.[5]

Criteria Score
Adults 65 years and older 1
Previous coronary artery stenosis > 50%
  • Cardiac catherterization
  • Angioplasty or stent
  • Bypass
  • Myocardial infraction
1
Cardiac risk factors (three or more)
  • Hypertension
  • Diabetes
  • High cholesterol
  • MI in family history
  • Tobacco history
1
Use of aspirin the previous week 1
Anginal events (two or more) in the previous day 1
ST segment alteration (>1mm elevation or depression) 1
Cardio bio-markers elevated 1

HEART Risk Score[6]

Factors Degree Score
History Highly suspicious

Moderately suspicious


Slightly suspicious

2

1


0

EGC Significant ST depression

Non-specific repolarisation disturbance


Normal

2

1


0

Age >65 years

45-65 years


<45 years

2

1


0

Risk Factors > 3 risk factors or history of atherosclerotic disease

1 or 2 risk factors


No risk factors

2

1


0

Troponin >3x the normal limit

1-3x the normal limit


< the normal limit

2

1


0

TOTAL
























GRACE Risk Score[7]

Factor Categories Score
Age (years) <40

40-49


50-59


60-69


70-79


>80

0

18


36


55


73


91

Heart Rate (bpm) <70

70-89


90-109


110-149


150-199


>200

0

7


13


23


36


46

Systolic Blood Pressure (mmHg) <80

80-99


100-119


120-139


140-159


160-199


>200

63

58


47


37


26


11


0

Creatinine (mg/dL) 0-0.39

0.4-0.79


0.8-1.19


1.2-1.59


1.6-1.99


2-3.99


>4

2

5


8


11


14


23


31

Killip Class Class I

Class II


Class III


Class IV

0

21


43


64


Cardiac arrest at admission 43
Elevated Cardiac Bio-markers 15
ST-segment deviation 30















































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.

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.

References

  1. "ACC/AHA 2004 guideline update for coronary arter... [Circulation. 2004] - PubMed - NCBI".
  2. 2.0 2.1 2.2 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.
  3. "http://eurheartj.oxfordjournals.org/content/32/23/2999.full.pdf" (PDF). External link in |title= (help)
  4. "http://eurheartj.oxfordjournals.org/content/32/23/2999.full.pdf" (PDF). External link in |title= (help)
  5. Antman EM, Cohen M, Bernink PJ, McCabe CH, Horacek T, Papuchis G; et al. (2000). "The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication and therapeutic decision making". JAMA. 284 (7): 835–42. PMID 10938172.
  6. Doucet S, Malekianpour M, Théroux P, Bilodeau L, Côté G, de Guise P; et al. (2000). "Randomized trial comparing intravenous nitroglycerin and heparin for treatment of unstable angina secondary to restenosis after coronary artery angioplasty". Circulation. 101 (9): 955–61. PMID 10704160.
  7. de Araújo Gonçalves P, Ferreira J, Aguiar C, Seabra-Gomes R (2005). "TIMI, PURSUIT, and GRACE risk scores: sustained prognostic value and interaction with revascularization in NSTE-ACS". Eur Heart J. 26 (9): 865–72. doi:10.1093/eurheartj/ehi187. PMID 15764619.
  8. 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.
  9. 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
  10. 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
  11. Anderson HV (1995). "Intravenous thrombolysis in refractory unstable angina pectoris". Lancet. 346 (8983): 1113–4. PMID 7475596.


Template:WikiDoc Sources