STEMI resident survival guide: Difference between revisions
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* [[Plaque rupture]] | * [[Plaque rupture]] | ||
* [[Takotsubo cardiomyopathy]] (also known as [[broken heart syndrome]] or [[stress cardiomyopathy]]) | * [[Takotsubo cardiomyopathy]] (also known as [[broken heart syndrome]] or [[stress cardiomyopathy]]) | ||
==Pre-Hospital Care== | ==Pre-Hospital Care== | ||
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❑ Non compressible vascular punctures | ❑ Non compressible vascular punctures | ||
|} | |} | ||
==Complete Diagnostic Approach== | |||
Shown below is an algorithm summarizing the diagnostic approach to [[STEMI]] based on the 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction.<ref name="O'GaraKushner2013">{{cite journal|last1=O'Gara|first1=Patrick T.|last2=Kushner|first2=Frederick G.|last3=Ascheim|first3=Deborah D.|last4=Casey|first4=Donald E.|last5=Chung|first5=Mina K.|last6=de Lemos|first6=James A.|last7=Ettinger|first7=Steven M.|last8=Fang|first8=James C.|last9=Fesmire|first9=Francis M.|last10=Franklin|first10=Barry A.|last11=Granger|first11=Christopher B.|last12=Krumholz|first12=Harlan M.|last13=Linderbaum|first13=Jane A.|last14=Morrow|first14=David A.|last15=Newby|first15=L. Kristin|last16=Ornato|first16=Joseph P.|last17=Ou|first17=Narith|last18=Radford|first18=Martha J.|last19=Tamis-Holland|first19=Jacqueline E.|last20=Tommaso|first20=Carl L.|last21=Tracy|first21=Cynthia M.|last22=Woo|first22=Y. Joseph|last23=Zhao|first23=David X.|title=2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction|journal=Journal of the American College of Cardiology|volume=61|issue=4|year=2013|pages=e78–e140|issn=07351097|doi=10.1016/j.jacc.2012.11.019}}</ref> | |||
<span style="font-size:85%"> '''Abbreviations:''' '''CABG:''' coronary artery bypass graft; '''ECG:''' electrocardiogram; '''LAD:''' left anterior descending; '''LBBB:''' left bundle branch block; '''MI:''' myocardial infraction; '''PCI:''' percutaneous coronary intervention </span> | |||
{{Family tree/start}} | |||
{{familytree | A01 | | A01=<div style="float: left; text-align: left; width: 35em; 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 medications<br> | |||
:❑ No relief with rest <br> | |||
:❑ Worse with time <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 [[MI]] <br> | |||
❑ Previous [[PCI]] or [[CABG]] <br> | |||
❑ Cardiac risk factors<br> | |||
:❑ [[Hypertension]] <br> | |||
:❑ [[Diabetes]] <br> | |||
:❑ [[Hypercholesterolemia]] <br> | |||
:❑ [[Smoking]] <br> | |||
:❑ [[Obesity]] <br> | |||
❑ List of medications | |||
---- | |||
'''Identify possible triggers:'''<br> | |||
❑ Physical exertion <br> | |||
❑ [[Stress|Psychological stress]] (anger, anxiety, bereavement, work related stress, natural disasters, wars or sporting events) <br> | |||
❑ [[Sexual activity]] <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: | |||
::❑ [[Cardiogenic shock]] (associated with [[tachycardia]] and end organ hypoperfusion), or | |||
::❑ [[Right ventricular MI]] (associated with increased [[jugular venous pressure]] and clear lung fields), or | |||
::❑ [[Bezold-Jarisch reflex]] (associated with either normal [[heart rate]] or [[bradycardia]]) | |||
:❑ Discrepancy between arms (suggestive or [[aortic dissection]]) | |||
:❑ Narrow [[pulse pressure]] (suggestive of [[heart failure]]) | |||
:❑ Wide [[pulse pressure]] (suggestive of [[mitral regurgitation]] or [[VSD]]) | |||
❑ [[Heart rate]] <br> | |||
:❑ [[Tachycardia]] (suggestive of [[heart failure]]) | |||
:❑ [[Bradycardia]] (suggestive of [[heart block]]) | |||
'''Pulses''' <br> | |||
❑ [[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]] | |||
:❑ [[Mitral regurgitation]]: blowing holosystolic murmur best heard at the apex | |||
:❑ [[VSD]]: holosystolic murmur along the left and right sternal border | |||
:❑ [[Free wall rupture]]: holosytolic murmur | |||
:❑ [[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]]) | |||
'''Signs of Right Ventricular MI:'''<br> | |||
❑ Elevated [[jugular venous pressure]] (suggestive of [[right ventricular MI]])<br> | |||
❑ Presence of [[hepatojugular reflux]] (suggestive of [[right ventricular MI]])<br> | |||
'''Lungs''' <br> | |||
❑ [[Rales]] (suggestive of [[heart failure]]) <br> | |||
</div>}} | |||
{{familytree | |!| | | }} | |||
{{familytree | D01 | | D01=<div style="float: left; text-align: left; width: 35em; padding:1em;">'''Rule out life threatening alternative diagnoses:'''<br> | |||
❑ [[Aortic dissection]] <br> (suggestive signs and symptoms: [[back pain]], interscapular pain, [[aortic regurgitation]], [[pulsus paradoxus]], [[blood pressure]] discrepancy between the arms) <br> | |||
❑ [[Pulmonary embolism]] <br> (suggestive signs and symptoms: acute onset of [[dyspnea]], [[tachypnea]], [[hemoptysis]], previous DVT) <br> | |||
❑ [[Cardiac tamponade]] <br> (suggestive signs and symptoms: [[hypotension]], [[jugular venous distention]], muffled [[heart sounds]])<br> | |||
❑ [[Tension pneumothorax]] <br> (suggestive signs and symptoms: sudden [[dyspnea]], [[tachycardia]], [[trauma|chest trauma]], unilateral absence of breath sounds)<br> | |||
❑ [[Esophageal rupture]] <br> (suggestive signs and symptoms: [[vomiting]], [[subcutaneous emphysema]])</div>}} | |||
{{familytree | |!| | | }} | |||
{{familytree | E01 | | E01=<div style="float: left; text-align: left; width: 35em; padding:1em;">'''Order labs and tests:''' <br> | |||
❑ [[ECG]] <br> | |||
❑ Biomarkers <br> | |||
:❑ [[Troponin|Troponin I]]<br> | |||
:❑ [[Creatinine kinase|CK-MB]] <br> | |||
❑ [[Creatinine]] <br> </div>}} | |||
{{familytree | |!| | | }} | |||
{{familytree | F01 | | F01=<div style="float: left; text-align: left; width: 35em; padding:1em;"> | |||
❑ Characterize [[ECG]] changes consistent with [[STEMI]] | |||
:❑ ST elevation in at least 2 contiguous leads of 2 mm (0.2 mV) in men or 1.5 mm (0.15 mV) in women in leads V2–V3 and/or of 1 mm (0.1mV) in other contiguous chest leads or the limb leads | |||
:❑ ST depression in at least two precordial leads V1-V4 (suggestive of posterior myocardial infarction) | |||
:❑ ST depression in several leads plus ST elevation in lead aVR (suggestive of occlusion of the [[left main]] or proximal [[LAD]] artery) | |||
:❑ New [[LBBB]] | |||
❑ Confirm the diagnosis based on an increase in [[troponin]] | |||
</div>}} | |||
{{familytree | |!| | | }} | |||
{{familytree | G01 | G01= <div style="float: left; text-align: left; width: 35em; padding:1em;"> '''Consider right ventricular MI in case of:''' | |||
❑ [[Hypotension]]<br> | |||
❑ Elevated [[jugular venous pressure]]<br> | |||
❑ Clear lung fields<br> | |||
❑ [[ECG]] changes suggestive of an [[inferior MI]] <br> | |||
:❑ ST elevation in leads [[Echocardiogram#Limb Leads|II]], [[Echocardiogram#Limb Leads|III]] and [[Echocardiogram#Limb Leads|aVF]] </div>}} | |||
{{familytree | |!| | }} | |||
{{familytree | H01 | H01= <div style="float: left; text-align: left; width: 35em; padding:1em;">'''Order a right sided ECG in all patients with ST elevation in leads [[II]], [[III]] and [[aVF]]''' <br> | |||
❑ Clearly label the [[ECG]] as right sided <br> | |||
❑ ST-segment elevation of >1 mm in lead V4R suggests a right ventricular [[MI]]</div>}} | |||
{{Family tree/end}} | |||
==Pre-Discharge Care== | ==Pre-Discharge Care== |
Revision as of 17:08, 25 April 2014
STEMI Resident Survival Guide Microchapters |
---|
Overview |
Causes |
Pre-Hospital Care |
FIRE |
Complete Diagnosis |
Pre-Discharge Care |
Long Term Management |
Do's |
Don'ts |
Gallery |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [2]; Rim Halaby, M.D. [3]
Overview
ST elevation myocardial infarction (STEMI) is a syndrome characterized by the presence of symptoms of myocardial ischemia associated with persistent ST elevation on electrocardiogram and elevated cardiac enzymes. The management of STEMI should be initiated without delay and the following timelines should be minimized (the 4 D's):
Door to Data
If a patient presents with chest discomfort, an electrocardiogram must be obtained immediately and no later than 5-10 minutes after arrival. In the patient with chest discomfort, an electrocardiogram should be obtained prior to obtaining insurance / payment information.
Data to Decision
If the electrocardiogram shows ST segment elevation, ST segment depression consistent with posterior MI, or a new left bundle branch block, a decision must be made within 5 to 10 minutes as to whether to administer a fibrinolytic agent or to proceed to primary angioplasty.
Decision to Drug or Device
Once a decision is made to administer a fibrinolytic agent or to proceed to primary angioplasty this should be carried out within 30 minutes.
Causes
Life Threatening Causes
STEMI is a life-threatening condition and must be treated as such irrespective of the underlying cause.
Common Causes
- Aortic dissection with propagation to the right coronary artery
- Cocaine
- Plaque rupture
- Takotsubo cardiomyopathy (also known as broken heart syndrome or stress cardiomyopathy)
Pre-Hospital Care
Pre-hospital care can begin in the ambulance by Emergency Medical Services (EMS) personnel and it can decrease the delay in the management of STEMI patients. EMS services are staffed by either volunteers, fire fighters, or highly trained paramedics and their services depends on their level of training. Pre-hopital care is different among countries depending on the availability of EMS and highly trained paramedics. In the United States, volunteers and fire fighters are permitted to initiate emergency care prior to the arrival of highly trained paramedics by beginning CPR and if adequately trained, can defibrillate the patient using an automatic external defibrillator. Early access to EMS is promoted by a 9-1-1 system.
Prehospital Care ❑ Check the vital signs
❑ Activate the cardiac cath team in the hospital | |||||||||
Initial Care
Shown below is an algorithm depicting the therapeutic approach to STEMI based on the 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction.[1]
Initial Treatment ❑ Administer 162 - 325 mg of non enteric aspirin
❑ Administer 2-4 L/min via nasal cannula oxygen when saturation <90%
❑ Administer beta-blockers (unless contraindicated)
❑ Administer sublingual nitroglycerin 0.4 mg every 5 minutes for a total of 3 doses
❑ Administer 80 mg atorvastatin | |||||||||||||||||||||||
❑ Determine if PCI is available | |||||||||||||||||||||||
PCI is available | PCI is not available | ||||||||||||||||||||||
First medical contact to device ≥ 120 min | First medical contact to device time ≤ 120 min | ||||||||||||||||||||||
❑ Primary PCI within 90 minutes | ❑ Fibrinolytic therapy within 30 min | ❑ Transfer for primary PCI | |||||||||||||||||||||
Confirm that the patient has one of the following indications: ❑ Symptoms of ischemia <12 hours (Class I, level of evidence A) | ❑ Confirm that the patient has one of the following indications:
❑ Confirm that the patient has no contraindications for fibrinolytics | ||||||||||||||||||||||
Administer ONE of the following antiplatelet agents (before or at the time of PCI):
Prasugrel is contraindicated in case of prior history of strokes or TIAs, active pathological bleeding, age ≥75 years of age, 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
Administer ONE of the following anticoagulant therapy:
| Administer ONE of the following fibrinolytic therapy ❑ Tenecteplase single IV bolus
❑ Reteplase 10 units IV boluses every 30 min
❑ Streptokinase 1.5 million units IV administered over 30-60 min Administer a P12Y2 inhibitor
Administer ONE of the following anticoagulant therapy
❑ Enoxaparin (for up to 8 days or until revascularization)
| ||||||||||||||||||||||
Consider urgent CABG if the coronary anatomy is not amenable to PCI and one of the following: ❑ Ongoing and recurrent ischemia | Transfer to a PCI-Capable hospital for non primary PCI, if there is: ❑ Cardiogenic shock (Class I, level of evidence B) | ||||||||||||||||||||||
Contraindications to Fibrinolytic Therapy
Shown below is a table summarizing the absolute and relative contraindications for fibrinolytic therapy among STEMI patients.
Absolute contraindications | Relative contraindications |
❑ Prior intracranial hemorrhage ❑ Ischemic stroke within the last 3 months (Unless within 4.5 hours) |
❑ Oral anticoagulation therapy ❑ Pregnancy |
Complete Diagnostic Approach
Shown below is an algorithm summarizing the diagnostic approach to STEMI based on the 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction.[1]
Abbreviations: CABG: coronary artery bypass graft; ECG: electrocardiogram; LAD: left anterior descending; LBBB: left bundle branch block; MI: myocardial infraction; PCI: percutaneous coronary intervention
Characterize the symptoms: ❑ Chest pain or chest discomfort
❑ Dyspnea | |||||||||
Obtain a detailed history: ❑ Age
❑ List of medications Identify possible triggers: | |||||||||
Examine the patient: Vital signs
Pulses
Skin Heart
❑ Murmurs
❑ Pericardial friction rub (suggestive of pericarditis) Signs of Right Ventricular MI: Lungs | |||||||||
Rule out life threatening alternative diagnoses: ❑ Aortic dissection (suggestive signs and symptoms: vomiting, subcutaneous emphysema) | |||||||||
❑ Characterize ECG changes consistent with STEMI
❑ Confirm the diagnosis based on an increase in troponin | |||||||||
Consider right ventricular MI in case of:
❑ Hypotension | |||||||||
Pre-Discharge Care
Administer the following medications in patients without contraindications: ❑ Aspirin 81-325 mg (indefinitely)
❑ ACE inhibitor in case of anterior MI, ejection fraction ≤ 40% or heart failure
❑ Valsartan (in case of intolerance to ACE inhibitors)
❑ Atorvastatin 80 mg daily Administer antiplatelet therapy For patients who underwent PCI, for one year Manage complications of STEMI
❑ Temporary pacing for asymptomatic bradycardia refractory to medical therapy (Class I, level of evidence C)
Assess the patient for ischemia: | |||||||||
Long Term Management
❑ Prepare a list of all the home medications and educate the patient about compliance
❑ Encourage lifestyle modification
❑ Ensure the initiation of the management of comorbidities
❑ Educate the patient about the early recognition of symptoms of MI | |||||||
Do's
- Pre-hospital ECG is recommended. If STEMI is diagnosed the PCI team should be activated while the patient is en route to the hospital.
- Administer reperfusion therapy for all patients presenting with STEMI within 12 hours of the beginning of the symptoms (Class I, level of evidence A).
- 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 nitroglycerins.[3]
- Discontinue non-steroidal anti-inflamatory drugs immediately.[4][5]
- Rule out any contraindications for fibrinolytic therapy before its administration. If contraindications to fibrinolytics are present, the patient should be transferred to another hospital where PCI is available.
- Initiate therapeutic hypothermia among comatose patients with STEMI (Class I, level of evidence B).
- Perform immediate angiography and PCI among STEMI patients who underwent resuscitation for cardiac arrest (Class I, level of evidence B).
- Consider bare-metal stent among STEMI patients with any of the following (Class I, level of evidence C):
- High bleeding risk
- Lack of compliance for a one year regimen of dual antiplatelet therapy
- Surgery or invasive procedure within the next year
- Achieve the following therapeutic activated clotting time when administering UFH:
- 200 to 250 seconds with the concomitant administration of GPIIbIIIa receptor inhibitor
- 250 to 300 seconds (HemoTec device) without the concomitant administration of a GPIIbIIIa receptor inhibitor
- 300 to 350 seconds (Hemochron device) without the concomitant administration of a GPIIbIIIa receptor inhibitor
- Make sure the dose of P2Y12 receptor inhibitors is appropriate among patients undergoing PCI after fibrinolytic therapy:
- Patients who already received a loading dose of clopidogrel: No loading dose, clopidogrel daily
- Patients who did not receive a loading dose of clopidogrel and PCI is performed ≤ 24 hours after fibrinolytic therapy: loading dose of 300 mg clopidogrel
- Patients who did not receive a loading dose of clopidogrel and PCI is performed > 24 hours after fibrinolytic therapy: loading dose of 600 mg clopidogrel
- Patients who did not receive a loading dose of clopidogrel and PCI is performed >24 hours after therapy with fibrin specific agent, or >48 hours after therapy with a non-fibrin-specific agent: prasugrel 60 mg
- Prepare the patient for urgent CABG when indicated by discontinuing the following:
- Clopidogrel or ticagrelor at least 24 hours prior to CABG
- Eptifibatide or tirofiban at least 2 to 4 hours prior to CABG
- Abciximab 12 hours prior to CABG
- Consider using a mechanical circulatory support among hemodynamically unstable patients with STEMI requiring an urgent CABG (Class IIa, level of evidence C).
- Recommend a long term maintenance dose of 81 mg of aspirin when the patient is administered ticagrelor.
- Include aldosterone antagonist in the discharge medication list among patients who are already on ACE inhibitors and beta-blockers with a left ventricular ejection fraction <40% or diabetes or heart failure.[1]
Don'ts
- Do not administer IV beta-blockers among patients with elevated risk for cardiogenic shock, signs of heart failure, low ouput state, prolonged PR interval more than 0.24 seconds, second or third degree block or asthma (Class I, level of evidence B).
- 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 nitroglycerine to patients with systolic BP < 90 mm Hg or ≥ to 30 mm Hg below baseline, severe bradycardia (< 50 bpm), tachycardia (> 100 bpm), or suspected right ventricular infarction.
- Do not delay the time for reperfusion.
- Do not administer prasugrel among patients with any of the following:
- Prior history of strokes or TIAs (Class III, Level of evidence B)
- Active pathological bleeding
- Age ≥75 years of age, (except in high-risk patients such as diabetes or prior MI, where its use may be considered)
- Urgent coronary artery bypass graft surgery (CABG) is likely
- Presence of additional risk factors for bleeding such as body weight <60 kg, propensity to bleed, concomitant use of medications that increase the risk of bleeding[6]
- Do not administer fibrinolytic therapy to patients with known cerebral arteriovenous malformation or to patients with suspected aortic dissection.
- Do not withhold aspirin among patients who are planned to undergo urgent CABG (Class I, level of evidence C).[1]
References
- ↑ 1.0 1.1 1.2 1.3 O'Gara, Patrick T.; Kushner, Frederick G.; Ascheim, Deborah D.; Casey, Donald E.; Chung, Mina K.; de Lemos, James A.; Ettinger, Steven M.; Fang, James C.; Fesmire, Francis M.; Franklin, Barry A.; Granger, Christopher B.; Krumholz, Harlan M.; Linderbaum, Jane A.; Morrow, David A.; Newby, L. Kristin; Ornato, Joseph P.; Ou, Narith; Radford, Martha J.; Tamis-Holland, Jacqueline E.; Tommaso, Carl L.; Tracy, Cynthia M.; Woo, Y. Joseph; Zhao, David X. (2013). "2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction". Journal of the American College of Cardiology. 61 (4): e78–e140. doi:10.1016/j.jacc.2012.11.019. ISSN 0735-1097.
- ↑ Epstein AE, Dimarco JP, Ellenbogen KA, Estes NA, Freedman RA, Gettes LS; et al. (2008). "ACC/AHA/HRS 2008 guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: executive summary". Heart Rhythm. 5 (6): 934–55. doi:10.1016/j.hrthm.2008.04.015. PMID 18534377.
- ↑ 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.
- ↑ 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
- ↑ 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
- ↑ "http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=5fe9c118-c44b-48d7-a142-9668ae3df0c6". Retrieved 6 February 2014. External link in
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