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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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