Acute coronary syndrome: Difference between revisions

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In [[medicine]] and [[cardiology]], '''acute coronary syndrome''' (ACS) is a collection of [[sign (medical)|signs]] and [[symptom]]s due to inadequate oxygenation of the heart muscle, the [[myocardium]], usually due to [[coronary artery disease]].<ref>{{MeSH}}</ref> ACS includes [[myocardial infarction]] ("heart attack") and  [[angina]].
Pain relief and proper oxygenation is the core of ACS treatment. When the root causie is angina, the temporary cause of ischemia should be reversed. For myocardial infarction, more vigorous interventions are appropriate if they can prevent damage to myocardium.
==Etiology/causes==
===Atheroclerotic obstruction===
ACS is usually caused by obstruction in an epicardial coronary artery.<ref name="pmid18687244">{{cite journal |author=Ong P, Athanasiadis A, Hill S, Vogelsberg H, Voehringer M, Sechtem U |title=Coronary artery spasm as a frequent cause of acute coronary syndrome: The CASPAR (Coronary Artery Spasm in Patients With Acute Coronary Syndrome) Study |journal=J. Am. Coll. Cardiol. |volume=52 |issue=7 |pages=523–7 |year=2008 |month=August |pmid=18687244 |doi=10.1016/j.jacc.2008.04.050 |url=http://linkinghub.elsevier.com/retrieve/pii/S0735-1097(08)01872-X |issn=}}</ref> The obstruction may be due to a thrombus at the site of a ruptured atherosclerotic plaque.<ref name="pmid1728732">{{cite journal |author=Mizuno K, Satomura K, Miyamoto A, ''et al'' |title=Angioscopic evaluation of coronary-artery thrombi in acute coronary syndromes |journal=N. Engl. J. Med. |volume=326 |issue=5 |pages=287–91 |year=1992 |month=January |pmid=1728732 |doi= |url= |issn=}}</ref>
Rupture seems more likely to occur during the morning hours.<ref name="pmid2865677">{{cite journal |author=Muller JE, Stone PH, Turi ZG, ''et al'' |title=Circadian variation in the frequency of onset of acute myocardial infarction |journal=N. Engl. J. Med. |volume=313 |issue=21 |pages=1315–22 |year=1985 |month=November |pmid=2865677 |doi= |url= |issn=}}</ref> Rupture may be precipited by inflammation from non-cardiac infections.<ref name="pmid18293142">{{cite journal |author=Harskamp RE, van Ginkel MW |title=Acute respiratory tract infections: a potential trigger for the acute coronary syndrome |journal=Ann. Med. |volume=40 |issue=2 |pages=121–8 |year=2008 |pmid=18293142 |doi=10.1080/07853890701753672 |url=http://www.informaworld.com/openurl?genre=article&doi=10.1080/07853890701753672&magic=pubmed&#124;&#124;1B69BA326FFE69C3F0A8F227DF8201D0 |issn=}}</ref> Rupture may be triggered by vigorous exercise among individuals who do not ordinarily do vigorous exercise.<ref name="pmid6472399">{{cite journal |author=Siscovick DS, Weiss NS, Fletcher RH, Lasky T |title=The incidence of primary cardiac arrest during vigorous exercise |journal=N. Engl. J. Med. |volume=311 |issue=14 |pages=874–7 |year=1984 |month=October |pmid=6472399 |doi= |url= |issn=}}</ref>
===Coronary vasospasm===
Approximately 15% of NSTEMI and 2% of STEMI patients have no obstruction of coronary vessels and in about half of these patients, spasm can be induced of a coronary artery.<ref name="pmid18687244"/>
===Emotional stress===
The role of emotional stress was supported in a study of the incidence of coronary events in the [[Munich]] area during the 2006 FIFA World Cup Football ([[soccer]]) championship.<ref name="pmid18234752">{{cite journal |author=Wilbert-Lampen U, Leistner D, Greven S, ''et al'' |title=Cardiovascular events during World Cup soccer |journal=N. Engl. J. Med. |volume=358 |issue=5 |pages=475–83 |year=2008 |pmid=18234752 |doi=10.1056/NEJMoa0707427 |issn=}}</ref> The incidence of coronary events was higher during the match, especially for people who had pre-existing coronary disease. Similar findings have been reported in [[Los Angeles, California|Los Angeles]], California during the American [[Super Bowl]].<ref name="pmid19539070">{{cite journal| author=Kloner RA, McDonald S, Leeka J, Poole WK| title=Comparison of total and cardiovascular death rates in the same city during a losing versus winning super bowl championship. | journal=Am J Cardiol | year= 2009 | volume= 103 | issue= 12 | pages= 1647-50 | pmid=19539070
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&email=badgett@uthscdsa.edu&retmode=ref&cmd=prlinks&id=19539070 | doi=10.1016/j.amjcard.2009.02.012 }} <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref> Stress, via increases in unhealthy behaviors, was also identified as more important than hypertension or [[C-reactive protein]] level in predicting coronary events.<ref name="pmid19095133">{{cite journal |author=Hamer M, Molloy GJ, Stamatakis E |title=Psychological distress as a risk factor for cardiovascular events pathophysiological and behavioral mechanisms |journal=J. Am. Coll. Cardiol. |volume=52 |issue=25 |pages=2156–62 |year=2008 |month=December |pmid=19095133 |doi=10.1016/j.jacc.2008.08.057 |url=http://content.onlinejacc.org/cgi/content/full/52/25/2156 |issn=}}</ref>
====Stress-induced (takotsubo) cardiomyopathy====
Stress-induced (takotsubo) cardiomyopathy may occur during acute medical illness or after intense emotional or physical stress.<ref name="pmid17573507">{{cite journal |author=Kurowski V, Kaiser A, von Hof K, ''et al'' |title=Apical and midventricular transient left ventricular dysfunction syndrome (tako-tsubo cardiomyopathy): frequency, mechanisms, and prognosis |journal=Chest |volume=132 |issue=3 |pages=809–16 |year=2007 |month=September |pmid=17573507 |doi=10.1378/chest.07-0608 |url=http://www.chestjournal.org/cgi/pmidlookup?view=long&pmid=17573507 |issn=}}</ref> It may be caused by [[catecholamine]]s.
==Classification==
==Classification==
{| class="wikitable"
|+Classification of acute coronary syndrome<ref name="pmid17692738">{{cite journal |author=Anderson JL, Adams CD, Antman EM, ''et al'' |title=ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-Elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction) developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine |journal=J. Am. Coll. Cardiol. |volume=50 |issue=7 |pages=e1–e157 |year=2007 |pmid=17692738 |doi=10.1016/j.jacc.2007.02.013|url=http://content.onlinejacc.org/cgi/content/full/50/7/e1}} [http://content.onlinejacc.org/cgi/content/full/50/7/652 Executive summary] [http://www.ngc.gov/summary/summary.aspx?ss=15&doc_id=11333 Summary at National Guidelines Clearinghouse]</ref>
|-
! &nbsp;
! [[Electrocardiogram]]
! Serum biomarkers
!Typical appearance of culprit vessel at angioscopy<ref name="pmid1728732">{{cite journal |author=Mizuno K, Satomura K, Miyamoto A, ''et al'' |title=Angioscopic evaluation of coronary-artery thrombi in acute coronary syndromes |journal=N. Engl. J. Med. |volume=326 |issue=5 |pages=287–91 |year=1992 |month=January |pmid=1728732 |doi= |url= |issn=}}</ref>
|-
| Unstable angina
| "ST-segment depression or prominent T-wave inversion"<ref name="pmid17692738"/>
| Normal
| Nonocclusive grayish-white thrombus<br/>(platelet-rich)
|-
| Non-ST segment elevation myocardial infarction<br>(NSTEMI)
| "ST-segment depression or prominent T-wave inversion"<ref name="pmid17692738"/>
| Elevated
| Primary NSTEMI: Nonocclusive grayish-white thrombus<br/>(platelet-rich)<br/>
Secondary NSTEMI: no thrombus
|-
| ST segment elevation myocardial infarction<br>(STEMI)
| ST-segment elevation
| Elevated
| Occlusive reddish thrombus <br/>(fibrin-rich)
|-
| Q-wave myocardial infarction
| Q-waves
| Elevated
| Occlusive reddish thrombus <br/>(fibrin-rich)
|}
===Unstable angina===
===Unstable angina===
Unstable angina is defined as "precordial pain at rest, which may precede a myocardial infarction".<ref>{{cite web |url=http://www.nlm.nih.gov/cgi/mesh/2007/MB_cgi?mode=&term=unstable+angina |title=Unstable angina|author=National Library of Medicine |accessdate=2007-10-28 |format= |work=}}</ref>
Unstable angina is defined as "precordial pain at rest, which may precede a myocardial infarction".<ref>{{cite web |url=http://www.nlm.nih.gov/cgi/mesh/2007/MB_cgi?mode=&term=unstable+angina |title=Unstable angina|author=National Library of Medicine |accessdate=2007-10-28 |format= |work=}}</ref>
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===Myocardial infarction===
===Myocardial infarction===
{{main|Myocardial infarction}}
{{main|Myocardial infarction}}
A myocardial infarction is defined as "gross necrosis of the myocardium, as a result of interruption of the blood supply to the area".<ref>{{cite web |url=http://www.nlm.nih.gov/cgi/mesh/2007/MB_cgi?mode=&term=unstable+angina |title=Myocardial infarction|author=National Library of Medicine |accessdate=2007-10-28 |format= |work=}}</ref>
A myocardial infarction is defined as "gross necrosis of the myocardium, as a result of interruption of the blood supply to the area".<ref>{{cite web |url=http://www.nlm.nih.gov/cgi/mesh/2007/MB_cgi?mode=&term=unstable+angina |title=Myocardial infarction|author=National Library of Medicine |accessdate=2007-10-28 |format= |work=}}</ref> It is usually caused by occlusion of an epicardial [[coronary artery]].<ref name="pmid7412821">{{cite journal |author=DeWood MA, Spores J, Notske R, ''et al'' |title=Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction |journal=N. Engl. J. Med. |volume=303 |issue=16 |pages=897–902 |year=1980 |month=October |pmid=7412821 |doi= |url= |issn=}}</ref>
 
====Non-ST segment elevation myocardial infarction (NSTEMI)====
NSTEMI is usually caused by a grayish-white [[thrombus]] that is [[platelet]]-rich.<ref name="pmid1728732">{{cite journal |author=Mizuno K, Satomura K, Miyamoto A, ''et al'' |title=Angioscopic evaluation of coronary-artery thrombi in acute coronary syndromes |journal=N. Engl. J. Med. |volume=326 |issue=5 |pages=287–91 |year=1992 |month=January |pmid=1728732 |doi= |url= |issn=}}</ref>
 
====ST segment elevation myocardial infarction (STEMI)====
STEMI is usually caused by a reddish [[thrombus]] that is [[fibrin]]-rich.<ref name="pmid1728732">{{cite journal |author=Mizuno K, Satomura K, Miyamoto A, ''et al'' |title=Angioscopic evaluation of coronary-artery thrombi in acute coronary syndromes |journal=N. Engl. J. Med. |volume=326 |issue=5 |pages=287–91 |year=1992 |month=January |pmid=1728732 |doi= |url= |issn=}}</ref>


==Diagnosis==
==Diagnosis==
The Acute Cardiac Ischemia Time-Insensitive Predictive Instrument (ACI-TIPI), a [[clinical prediction rule]], can help diagnose patients with chest pain.<ref name="pmid9867725">{{cite journal |author=Selker HP, Beshansky JR, Griffith JL, ''et al'' |title=Use of the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI) to assist with triage of patients with chest pain or other symptoms suggestive of acute cardiac ischemia. A multicenter, controlled clinical trial |journal=Ann. Intern. Med. |volume=129 |issue=11 |pages=845–55 |year=1998 |pmid=9867725 |doi=}}</ref>
Various protocols that combine findings from the medical history, [[physical examination]], and [[diagnostic test]]s have been studied.<ref name="pmid22892889">{{cite journal| author=Reichlin T, Schindler C, Drexler B, Twerenbold R, Reiter M, Zellweger C et al.| title=One-Hour Rule-out and Rule-in of Acute Myocardial Infarction Using High-Sensitivity Cardiac Troponin T. | journal=Arch Intern Med | year= 2012 | volume=  | issue=  | pages= 1-8 | pmid=22892889 | doi=10.1001/archinternmed.2012.3698 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22892889  }} </ref><ref name="pmid22805631">{{cite journal| author=Jalili M, Hejripour Z, Honarmand AR, Pourtabatabaei N| title=Validation of the vancouver chest pain rule: a prospective cohort study. | journal=Acad Emerg Med | year= 2012 | volume= 19 | issue= 7 | pages= 837-42 | pmid=22805631 | doi=10.1111/j.1553-2712.2012.01399.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22805631  }} </ref><ref name="pmid22221842">{{cite journal| author=Scheuermeyer FX, Innes G, Grafstein E, Kiess M, Boychuk B, Yu E et al.| title=Safety and efficiency of a chest pain diagnostic algorithm with selective outpatient stress testing for emergency department patients with potential ischemic chest pain. | journal=Ann Emerg Med | year= 2012 | volume= 59 | issue= 4 | pages= 256-264.e3 | pmid=22221842 | doi=10.1016/j.annemergmed.2011.10.016 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22221842  }} </ref>
 
===History and physical examination===
A helpful finding is exact reproduction of chest pain upon palpating the chest.<ref>Lee TH, Cook EF, Weisberg M, Sargent RK, Wilson C, Goldman L. Acute chest pain in the emergency room. Identification and examination of low-risk patients. Arch Intern Med. 1985 Jan;145(1):65-9. PMID 3970650</ref> In a patient whose other findings also suggest a non-cardiac course of their chest pain, this finding can help rule out coronary disease.<ref name="pmid18307844">{{cite journal |author=Bruyninckx R, Aertgeerts B, Bruyninckx P, Buntinx F |title=Signs and symptoms in diagnosing acute myocardial infarction and acute coronary syndrome: a diagnostic meta-analysis |journal=Br J Gen Pract |volume=58 |issue=547 |pages=105–11 |year=2008 |month=February |pmid=18307844 |doi=10.3399/bjgp08X277014 |url=http://openurl.ingenta.com/content/nlm?genre=article&issn=0960-1643&volume=58&issue=547&spage=105&aulast=Bruyninckx |issn=}}</ref>
 
===Electrocardiogram===
The [[electrocardiogram]] is a key part of decision making. For example, the presence of ST changes and Q-waves determines therapy.
 
A normal [[electrocardiogram]] has been reported ''not'' to exclude acute coronary syndrome, even when the [[electrocardiogram]] is taken during pain.<ref>{{Cite journal | doi = 10.1111/j.1553-2712.2009.00420.x | volume = 16
| issue = 6 | pages = 495-499 | last = Turnipseed | first = Samuel D. | coauthors = William S. Trythall, Deborah B. Diercks, Erik G. Laurin, J. Douglas Kirk, David S. Smith, David N. Main, Ezra A. Amsterdam
| title = Frequency of Acute Coronary Syndrome in Patients with Normal Electrocardiogram Performed during Presence or Absence of Chest Pain | journal = Academic Emergency Medicine | accessdate = 2009-06-13 | date = 2009 | url = http://dx.doi.org/10.1111/j.1553-2712.2009.00420.x }}</ref> Although this study defined unstable angina as either a coronary stenosis or positive stress test and so likely includes patients without true acute coronary syndrome as defined by the American Heart Association<ref name="pmid17692738" />, the study was still not able to show that a normal electrocardiogram helped exclude a NSTEMI.
 
Isolated abnormalities of T-waves also confers worse prognosis.<ref name="pmid18616439">{{cite journal |author=Lin KB, Shofer FS, McCusker C, Meshberg E, Hollander JE |title=Predictive value of T-wave abnormalities at the time of emergency department presentation in patients with potential acute coronary syndromes |journal=Acad Emerg Med |volume=15 |issue=6 |pages=537–43 |year=2008 |month=June |pmid=18616439 |doi=10.1111/j.1553-2712.2008.00135.x |url=http://dx.doi.org/10.1111/j.1553-2712.2008.00135.x |issn=}}</ref>
 
===Computed tomographic cardiac angiography===
[[Computed tomographic cardiac angiography]] may reduce the rate of [[hospital admission]]s.<ref name="pmid22449295">{{cite journal| author=Litt HI, Gatsonis C, Snyder B, Singh H, Miller CD, Entrikin DW et al.| title=CT angiography for safe discharge of patients with possible acute coronary syndromes. | journal=N Engl J Med | year= 2012 | volume= 366 | issue= 15 | pages= 1393-403 | pmid=22449295 | doi=10.1056/NEJMoa1201163 | pmc= | url= }} </ref>
 
===Laboratory tests===
{{main|Troponin}}
[[Clinical practice guideline]]s anchor the diagnosis on [[troponin]] blood assays obtained within 6 hours and again within 8-12 hours of a patient arriving for medical care.<ref name="pmid17692738" />
 
===Clinical prediction rules===
The [[Thrombolysis in Myocardial Infarction risk score for unstable angina or non-ST elevation myocardial infarction]] is a [[clinical prediction rule]] that may detect patients with chest pain who are at increased risk of [[acute coronary syndrome]]<ref name="pmid19041531">{{cite journal| author=Campbell CF, Chang AM, Sease KL, Follansbee C, McCusker CM, Shofer FS et al.| title=Combining Thrombolysis in Myocardial Infarction risk score and clear-cut alternative diagnosis for chest pain risk stratification. | journal=Am J Emerg Med | year= 2009 | volume= 27 | issue= 1 | pages= 37-42 | pmid=19041531 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19041531 | doi=10.1016/j.ajem.2008.01.028 }} </ref><ref name="pmid16365321">{{cite journal| author=Pollack CV, Sites FD, Shofer FS, Sease KL, Hollander JE| title=Application of the TIMI risk score for unstable angina and non-ST elevation acute coronary syndrome to an unselected emergency department chest pain population. | journal=Acad Emerg Med | year= 2006 | volume= 13 | issue= 1 | pages= 13-8 | pmid=16365321 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16365321 | doi=10.1197/j.aem.2005.06.031 }} </ref>
 
A second [[clinical prediction rule]], the Acute Cardiac Ischemia Time-Insensitive Predictive Instrument (ACI-TIPI) can help diagnose patients with chest pain and has been shown to improve medical care in a [[randomized controlled trial]].<ref name="pmid9867725">{{cite journal |author=Selker HP, Beshansky JR, Griffith JL, ''et al'' |title=Use of the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI) to assist with triage of patients with chest pain or other symptoms suggestive of acute cardiac ischemia. A multicenter, controlled clinical trial |journal=Ann. Intern. Med. |volume=129 |issue=11 |pages=845–55 |year=1998 |pmid=9867725 |doi=|url=http://www.annals.org/cgi/content/full/129/11_Part_1/845}} [http://www.infopoems.com/irsearch/display_article.cfm?resource=R&article=30 Online calculator at InfoRetriever]</ref><ref name="pmid2072767">{{cite journal |author=Selker HP, Griffith JL, D'Agostino RB |title=A tool for judging coronary care unit admission appropriateness, valid for both real-time and retrospective use. A time-insensitive predictive instrument (TIPI) for acute cardiac ischemia: a multicenter study |journal=Med Care |volume=29 |issue=7 |pages=610–27 |year=1991 |pmid=2072767 |doi=|url=http://www.jstor.org/view/00257079/ap060296/06a00030/0}}</ref> The ACI-TIPI was studied up through 1993 before troponin assays were widely available and thus does not incorporate the troponin. However, the ACI-TIPI should retain its ability to use the medical history and the EKG to decide who should be observed for serial troponin levels. It is unclear why this role is not recognized by the ACC/AHA guidelines. One reason may be that the ACI-TIPI is patented.<ref name="USPAT5718233>{{cite web |url=http://www.google.com/patents?vid=USPAT5718233 |title=Continuous monitoring using a predictive instrument|author=Selker HP et al. |accessdate=2007-11-29 |format= |work=}}</ref><ref name="USPAT5724983">{{cite web |url=http://www.google.com/patents?vid=USPAT5724983 |title=Continuous monitoring using a predictive instrument|author=Selker HP et al. |accessdate=2007-11-29 |format= |work=}}</ref>
 
A third [[clinical prediction rule]], also prior to availability of troponin tests, was created by Pozen.<ref name="pmid6371525">{{cite journal| author=Pozen MW, D'Agostino RB, Selker HP, Sytkowski PA, Hood WB| title=A predictive instrument to improve coronary-care-unit admission practices in acute ischemic heart disease. A prospective multicenter clinical trial. | journal=N Engl J Med | year= 1984 | volume= 310 | issue= 20 | pages= 1273-8 | pmid=6371525 | doi=10.1056/NEJM198405173102001 }} </ref> The rule is [http://www.nejm.org/doi/full/10.1056/NEJM198411083111913 available online] through the New England Journal of Medicine website.
 
Another [[clinical prediction rule]] is the [http://emed.wustl.edu/images/journal_club/2006/September_2006/Vancouver_Chest_Pain_Rule.pdf Vancouver Chest Pain Rule].<ref name="pmid16387209">{{cite journal| author=Christenson J, Innes G, McKnight D, Thompson CR, Wong H, Yu E et al.| title=A clinical prediction rule for early discharge of patients with chest pain. | journal=Ann Emerg Med | year= 2006 | volume= 47 | issue= 1 | pages= 1-10 | pmid=16387209 | doi=10.1016/j.annemergmed.2005.08.007 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16387209  }} </ref> In an independent validation study, "a lower  sensitivity and higher specificity when applying the Vancouver Chest  Pain Rule...as compared to the original study.". <ref  name="pmid22805631" />


==Treatment==
==Treatment==
[[Clinical practice guideline]]s address the treatment of unstable angina and non-ST-elevation [[myocardial infarction]].<ref name="pmid17692738">{{cite journal |author=Anderson JL, Adams CD, Antman EM, ''et al'' |title=ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-Elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction) developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine |journal=J. Am. Coll. Cardiol. |volume=50 |issue=7 |pages=e1–e157 |year=2007 |pmid=17692738 |doi=10.1016/j.jacc.2007.02.013}}</ref>
[[Clinical practice guideline]]s address the treatment of unstable angina and non-ST-elevation [[myocardial infarction]].<ref name="pmid17692738" /><ref name="pmid12383588">{{cite journal |author=Braunwald E, Antman EM, Beasley JW, ''et al'' |title=ACC/AHA 2002 guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction--summary article: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (Committee on the Management of Patients With Unstable Angina) |journal=J. Am. Coll. Cardiol. |volume=40 |issue=7 |pages=1366–74 |year=2002 |pmid=12383588 |doi=|url=http://content.onlinejacc.org/cgi/content/full/50/7/652}}</ref>
 
In the absence of specific contraindications, [[aspirin]] may be of benefit, both in the prehospital and emergency department settings, for all forms of ACS. <ref>{{citation
| Emerg Med J.
| date = 2001 November | volume = 18 | issue = 6 | pages = 478–481
| doi= 10.1136/emj.18.6.478.
| PMCID = PMC1725743
| title = Pre-hospital aspirin for suspected myocardial infarction and acute coronary syndromes: A headache for paramedics?
| author = M Woollard, A Smith, and P Elwood
| url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1725743/pdf/v018p00478.pdf}}</ref>
 
Patients without contraindication should receive [[anticoagulation]] with unfractionated [[heparin]].<ref name="pmid19458369">{{cite journal |author=Hillis LD, Lange RA |title=Optimal management of acute coronary syndromes |journal=N. Engl. J. Med. |volume=360 |issue=21 |pages=2237–40 |year=2009 |month=May |pmid=19458369 |doi=10.1056/NEJMe0902632 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=19458369&promo=ONFLNS19 |issn=}}</ref> The risk of bleeding can be estimated with a clinical prediction rule (http://www.crusadebleedingscore.org/).
===Unstable angina or NSTEMI===
====Adrenergic beta-antagonists====
[[Adrenergic beta-antagonist]]s (beta-blockers) are effective according to a [[systematic review]]<ref name="pmid10381708">{{cite journal |author=Freemantle N, Cleland J, Young P, Mason J, Harrison J |title=beta Blockade after myocardial infarction: systematic review and meta regression analysis |journal=BMJ |volume=318 |issue=7200 |pages=1730–7 |year=1999 |month=June |pmid=10381708 |pmc=31101 |doi= |url=http://bmj.com/cgi/pmidlookup?view=long&pmid=10381708 |issn=}}</ref>
 
====Platelet ADP receptor blockers====
[[Thienopyridine]] ADP blockers such as [[clopidogrel]], [[ticlopidine]], and the prodrug [[prasugrel]] may help especially for patients undergoing [[percutaneous coronary intervention]] (PCI). [[Ticagrelor]] may be better than clopidogrel for some patients.<ref name="pmid19717846">{{cite journal| author=Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C et al.| title=Ticagrelor versus clopidogrel in patients with acute coronary syndromes. | journal=N Engl J Med | year= 2009 | volume= 361 | issue= 11 | pages= 1045-57 | pmid=19717846
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&email=badgett@uthscdsa.edu&retmode=ref&cmd=prlinks&id=19717846 | doi=10.1056/NEJMoa0904327 }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&email=badgett@uthscdsa.edu&retmode=ref&cmd=prlinks&id=20008753 Review in: Ann Intern Med. 2009 Dec 15;151(12):JC6-4] <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref><ref>(2010) Lancet. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2809%2962191-7/fulltext Comparison of ticagrelor with clopidogrel in patients with a planned invasive strategy for acute coronary syndromes (PLATO): a randomised double-blind study]</ref>
 
====Glycoprotein IIb/IIIa inhibitors====
Glycoprotein IIb/IIIa inhibitors such as eptifibatide should not be given until after [[percutaneous transluminal coronary angioplasty]].<ref name="pmid">{{cite journal |author=Giugliano RP, White JA, Bode C, ''et al.'' |title=Early versus delayed, provisional eptifibatide in acute coronary syndromes |journal=N. Engl. J. Med. |volume=360 |issue=21 |pages=2176–90 |year=2009 |month=May |pmid= |doi=10.1056/NEJMoa0901316 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=19332455&promo=ONFLNS19 |issn=}}</ref>
 
====Percutaneous transluminal coronary angioplasty====
Among patients with unstable angina or NSTEMI and without ST-segment elevation (but may have other EKG evidence of ischemia such as ST-segment depression of ≥1 mm or transient ST-segment elevation or T-wave inversion of >3 mm) may benefit from early invasive management ([[percutaneous transluminal coronary angioplasty]]) if:
* [[Thrombolysis in Myocardial Infarction (TIMI) risk score]] of 3 or more, elevated myocardial enzymes, or elderly patients according to the TACTICS [[randomized controlled trial]].<ref name="pmid11419424">{{cite journal |author=Cannon CP, Weintraub WS, Demopoulos LA, ''et al'' |title=Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban |journal=N. Engl. J. Med. |volume=344 |issue=25 |pages=1879-87 |year=2001 |pmid=11419424 |doi= |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=11419424&promo=ONFLNS19 |issn=}}</ref><ref name="pmid15289215">{{cite journal |author=Bach RG, Cannon CP, Weintraub WS, ''et al'' |title=The effect of routine, early invasive management on outcome for elderly patients with non-ST-segment elevation acute coronary syndromes |journal=Ann. Intern. Med. |volume=141 |issue=3 |pages=186-95 |year=2004 |pmid=15289215 |doi=}}</ref>
* A [http://www.outcomes-umassmed.org/grace/acs_risk/acs_risk_content.html GRACE risk score] is more than 140 according to the TIMACS [[randomized controlled trial]].<ref name="pmid19458363">{{cite journal |author=Mehta SR, Granger CB, Boden WE, ''et al.'' |title=Early versus delayed invasive intervention in acute coronary syndromes |journal=N. Engl. J. Med. |volume=360 |issue=21 |pages=2165–75 |year=2009 |month=May |pmid=19458363 |doi=10.1056/NEJMoa0807986 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=19458363&promo=ONFLNS19 |issn=}}</ref>
 
In patients without ST-segment elevation on the [[electrocardiogram]], urgent [[angioplasty]] may occur anytime within the first 24 hours according to a [[randomized controlled trial]].<ref name="pmid19724041">{{cite journal| author=Montalescot G, Cayla G, Collet JP, Elhadad S, Beygui F, Le Breton H et al.| title=Immediate vs delayed intervention for acute coronary syndromes: a randomized clinical trial. | journal=JAMA | year= 2009 | volume= 302 | issue= 9 | pages= 947-54 | pmid=19724041 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&email=badgett@uthscdsa.edu&retmode=ref&cmd=prlinks&id=19724041 | doi=10.1001/jama.2009.1267 }}</ref>
 
===Myocardial infarction===
{{main|Myocardial infarction}}


==Prognosis==
==Prognosis==
The Thrombolysis in Myocardial Infarction [TIMI] [[clinical prediction rule]] can predict the likelihood of morbidity in patients with unstable angina or NSTEMI.<ref name="pmid10938172">{{cite journal |author=Antman EM, Cohen M, Bernink PJ, ''et al'' |title=The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication and therapeutic decision making |journal=JAMA |volume=284 |issue=7 |pages=835–42 |year=2000 |pmid=10938172 |doi=|url=http://jama.ama-assn.org/cgi/content/full/284/7/835}}</ref> The TIMI risk score is:
Three clinical prediction rules can help prognosticate with similar ability:<ref name="pmid15764619">{{cite journal |author=de Araújo Gonçalves P, Ferreira J, Aguiar C, Seabra-Gomes R |title=TIMI, PURSUIT, and GRACE risk scores: sustained prognostic value and interaction with revascularization in NSTE-ACS |journal=Eur. Heart J. |volume=26 |issue=9 |pages=865–72 |year=2005 |month=May |pmid=15764619 |doi=10.1093/eurheartj/ehi187 |url=http://eurheartj.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=15764619 |issn=}}</ref>
* Age 65 years or older
* [http://www.outcomes-umassmed.org/grace/acs_risk/acs_risk_content.html GRACE Risk Score]
* At least 3 risk factors for coronary artery disease (family history or [[coronary disease]], [[hypertension]], [[hypercholesterolemia]], [[diabetes]], current smoking)
* The Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) risk model
* Prior coronary stenosis of 50% or more
* [[Thrombolysis in Myocardial Infarction (TIMI) risk score]]
* ST-segment deviation on electrocardiogram at presentation
 
* At least 2 anginal events in prior 24 hours
These rules can help estimate prognosis and guide decisions.
* Use of aspirin in prior 7 days
* Elevated serum cardiac markers


==References==
==References==
<references/>
<references/>[[Category:Suggestion Bot Tag]]
 
[[Category:CZ Live]] [[Category:Health Sciences Workgroup]]

Latest revision as of 11:00, 6 July 2024

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Main Article
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In medicine and cardiology, acute coronary syndrome (ACS) is a collection of signs and symptoms due to inadequate oxygenation of the heart muscle, the myocardium, usually due to coronary artery disease.[1] ACS includes myocardial infarction ("heart attack") and angina.

Pain relief and proper oxygenation is the core of ACS treatment. When the root causie is angina, the temporary cause of ischemia should be reversed. For myocardial infarction, more vigorous interventions are appropriate if they can prevent damage to myocardium.

Etiology/causes

Atheroclerotic obstruction

ACS is usually caused by obstruction in an epicardial coronary artery.[2] The obstruction may be due to a thrombus at the site of a ruptured atherosclerotic plaque.[3]

Rupture seems more likely to occur during the morning hours.[4] Rupture may be precipited by inflammation from non-cardiac infections.[5] Rupture may be triggered by vigorous exercise among individuals who do not ordinarily do vigorous exercise.[6]

Coronary vasospasm

Approximately 15% of NSTEMI and 2% of STEMI patients have no obstruction of coronary vessels and in about half of these patients, spasm can be induced of a coronary artery.[2]

Emotional stress

The role of emotional stress was supported in a study of the incidence of coronary events in the Munich area during the 2006 FIFA World Cup Football (soccer) championship.[7] The incidence of coronary events was higher during the match, especially for people who had pre-existing coronary disease. Similar findings have been reported in Los Angeles, California during the American Super Bowl.[8] Stress, via increases in unhealthy behaviors, was also identified as more important than hypertension or C-reactive protein level in predicting coronary events.[9]

Stress-induced (takotsubo) cardiomyopathy

Stress-induced (takotsubo) cardiomyopathy may occur during acute medical illness or after intense emotional or physical stress.[10] It may be caused by catecholamines.

Classification

Classification of acute coronary syndrome[11]
  Electrocardiogram Serum biomarkers Typical appearance of culprit vessel at angioscopy[3]
Unstable angina "ST-segment depression or prominent T-wave inversion"[11] Normal Nonocclusive grayish-white thrombus
(platelet-rich)
Non-ST segment elevation myocardial infarction
(NSTEMI)
"ST-segment depression or prominent T-wave inversion"[11] Elevated Primary NSTEMI: Nonocclusive grayish-white thrombus
(platelet-rich)

Secondary NSTEMI: no thrombus

ST segment elevation myocardial infarction
(STEMI)
ST-segment elevation Elevated Occlusive reddish thrombus
(fibrin-rich)
Q-wave myocardial infarction Q-waves Elevated Occlusive reddish thrombus
(fibrin-rich)

Unstable angina

Unstable angina is defined as "precordial pain at rest, which may precede a myocardial infarction".[12]

Myocardial infarction

For more information, see: Myocardial infarction.

A myocardial infarction is defined as "gross necrosis of the myocardium, as a result of interruption of the blood supply to the area".[13] It is usually caused by occlusion of an epicardial coronary artery.[14]

Non-ST segment elevation myocardial infarction (NSTEMI)

NSTEMI is usually caused by a grayish-white thrombus that is platelet-rich.[3]

ST segment elevation myocardial infarction (STEMI)

STEMI is usually caused by a reddish thrombus that is fibrin-rich.[3]

Diagnosis

Various protocols that combine findings from the medical history, physical examination, and diagnostic tests have been studied.[15][16][17]

History and physical examination

A helpful finding is exact reproduction of chest pain upon palpating the chest.[18] In a patient whose other findings also suggest a non-cardiac course of their chest pain, this finding can help rule out coronary disease.[19]

Electrocardiogram

The electrocardiogram is a key part of decision making. For example, the presence of ST changes and Q-waves determines therapy.

A normal electrocardiogram has been reported not to exclude acute coronary syndrome, even when the electrocardiogram is taken during pain.[20] Although this study defined unstable angina as either a coronary stenosis or positive stress test and so likely includes patients without true acute coronary syndrome as defined by the American Heart Association[11], the study was still not able to show that a normal electrocardiogram helped exclude a NSTEMI.

Isolated abnormalities of T-waves also confers worse prognosis.[21]

Computed tomographic cardiac angiography

Computed tomographic cardiac angiography may reduce the rate of hospital admissions.[22]

Laboratory tests

For more information, see: Troponin.

Clinical practice guidelines anchor the diagnosis on troponin blood assays obtained within 6 hours and again within 8-12 hours of a patient arriving for medical care.[11]

Clinical prediction rules

The Thrombolysis in Myocardial Infarction risk score for unstable angina or non-ST elevation myocardial infarction is a clinical prediction rule that may detect patients with chest pain who are at increased risk of acute coronary syndrome[23][24]

A second clinical prediction rule, the Acute Cardiac Ischemia Time-Insensitive Predictive Instrument (ACI-TIPI) can help diagnose patients with chest pain and has been shown to improve medical care in a randomized controlled trial.[25][26] The ACI-TIPI was studied up through 1993 before troponin assays were widely available and thus does not incorporate the troponin. However, the ACI-TIPI should retain its ability to use the medical history and the EKG to decide who should be observed for serial troponin levels. It is unclear why this role is not recognized by the ACC/AHA guidelines. One reason may be that the ACI-TIPI is patented.[27][28]

A third clinical prediction rule, also prior to availability of troponin tests, was created by Pozen.[29] The rule is available online through the New England Journal of Medicine website.

Another clinical prediction rule is the Vancouver Chest Pain Rule.[30] In an independent validation study, "a lower sensitivity and higher specificity when applying the Vancouver Chest Pain Rule...as compared to the original study.". [16]

Treatment

Clinical practice guidelines address the treatment of unstable angina and non-ST-elevation myocardial infarction.[11][31]

In the absence of specific contraindications, aspirin may be of benefit, both in the prehospital and emergency department settings, for all forms of ACS. [32]

Patients without contraindication should receive anticoagulation with unfractionated heparin.[33] The risk of bleeding can be estimated with a clinical prediction rule (http://www.crusadebleedingscore.org/).

Unstable angina or NSTEMI

Adrenergic beta-antagonists

Adrenergic beta-antagonists (beta-blockers) are effective according to a systematic review[34]

Platelet ADP receptor blockers

Thienopyridine ADP blockers such as clopidogrel, ticlopidine, and the prodrug prasugrel may help especially for patients undergoing percutaneous coronary intervention (PCI). Ticagrelor may be better than clopidogrel for some patients.[35][36]

Glycoprotein IIb/IIIa inhibitors

Glycoprotein IIb/IIIa inhibitors such as eptifibatide should not be given until after percutaneous transluminal coronary angioplasty.[37]

Percutaneous transluminal coronary angioplasty

Among patients with unstable angina or NSTEMI and without ST-segment elevation (but may have other EKG evidence of ischemia such as ST-segment depression of ≥1 mm or transient ST-segment elevation or T-wave inversion of >3 mm) may benefit from early invasive management (percutaneous transluminal coronary angioplasty) if:

In patients without ST-segment elevation on the electrocardiogram, urgent angioplasty may occur anytime within the first 24 hours according to a randomized controlled trial.[41]

Myocardial infarction

For more information, see: Myocardial infarction.


Prognosis

Three clinical prediction rules can help prognosticate with similar ability:[42]

These rules can help estimate prognosis and guide decisions.

References

  1. Anonymous (2024), Acute coronary syndrome (English). Medical Subject Headings. U.S. National Library of Medicine.
  2. 2.0 2.1 Ong P, Athanasiadis A, Hill S, Vogelsberg H, Voehringer M, Sechtem U (August 2008). "Coronary artery spasm as a frequent cause of acute coronary syndrome: The CASPAR (Coronary Artery Spasm in Patients With Acute Coronary Syndrome) Study". J. Am. Coll. Cardiol. 52 (7): 523–7. DOI:10.1016/j.jacc.2008.04.050. PMID 18687244. Research Blogging.
  3. 3.0 3.1 3.2 3.3 Mizuno K, Satomura K, Miyamoto A, et al (January 1992). "Angioscopic evaluation of coronary-artery thrombi in acute coronary syndromes". N. Engl. J. Med. 326 (5): 287–91. PMID 1728732[e]
  4. Muller JE, Stone PH, Turi ZG, et al (November 1985). "Circadian variation in the frequency of onset of acute myocardial infarction". N. Engl. J. Med. 313 (21): 1315–22. PMID 2865677[e]
  5. Harskamp RE, van Ginkel MW (2008). "Acute respiratory tract infections: a potential trigger for the acute coronary syndrome". Ann. Med. 40 (2): 121–8. DOI:10.1080/07853890701753672. PMID 18293142. Research Blogging.
  6. Siscovick DS, Weiss NS, Fletcher RH, Lasky T (October 1984). "The incidence of primary cardiac arrest during vigorous exercise". N. Engl. J. Med. 311 (14): 874–7. PMID 6472399[e]
  7. Wilbert-Lampen U, Leistner D, Greven S, et al (2008). "Cardiovascular events during World Cup soccer". N. Engl. J. Med. 358 (5): 475–83. DOI:10.1056/NEJMoa0707427. PMID 18234752. Research Blogging.
  8. Kloner RA, McDonald S, Leeka J, Poole WK (2009). "Comparison of total and cardiovascular death rates in the same city during a losing versus winning super bowl championship.". Am J Cardiol 103 (12): 1647-50. DOI:10.1016/j.amjcard.2009.02.012. PMID 19539070. Research Blogging.
  9. Hamer M, Molloy GJ, Stamatakis E (December 2008). "Psychological distress as a risk factor for cardiovascular events pathophysiological and behavioral mechanisms". J. Am. Coll. Cardiol. 52 (25): 2156–62. DOI:10.1016/j.jacc.2008.08.057. PMID 19095133. Research Blogging.
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  19. Bruyninckx R, Aertgeerts B, Bruyninckx P, Buntinx F (February 2008). "Signs and symptoms in diagnosing acute myocardial infarction and acute coronary syndrome: a diagnostic meta-analysis". Br J Gen Pract 58 (547): 105–11. DOI:10.3399/bjgp08X277014. PMID 18307844. Research Blogging.
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  21. Lin KB, Shofer FS, McCusker C, Meshberg E, Hollander JE (June 2008). "Predictive value of T-wave abnormalities at the time of emergency department presentation in patients with potential acute coronary syndromes". Acad Emerg Med 15 (6): 537–43. DOI:10.1111/j.1553-2712.2008.00135.x. PMID 18616439. Research Blogging.
  22. Litt HI, Gatsonis C, Snyder B, Singh H, Miller CD, Entrikin DW et al. (2012). "CT angiography for safe discharge of patients with possible acute coronary syndromes.". N Engl J Med 366 (15): 1393-403. DOI:10.1056/NEJMoa1201163. PMID 22449295. Research Blogging.
  23. Campbell CF, Chang AM, Sease KL, Follansbee C, McCusker CM, Shofer FS et al. (2009). "Combining Thrombolysis in Myocardial Infarction risk score and clear-cut alternative diagnosis for chest pain risk stratification.". Am J Emerg Med 27 (1): 37-42. DOI:10.1016/j.ajem.2008.01.028. PMID 19041531. Research Blogging.
  24. Pollack CV, Sites FD, Shofer FS, Sease KL, Hollander JE (2006). "Application of the TIMI risk score for unstable angina and non-ST elevation acute coronary syndrome to an unselected emergency department chest pain population.". Acad Emerg Med 13 (1): 13-8. DOI:10.1197/j.aem.2005.06.031. PMID 16365321. Research Blogging.
  25. Selker HP, Beshansky JR, Griffith JL, et al (1998). "Use of the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI) to assist with triage of patients with chest pain or other symptoms suggestive of acute cardiac ischemia. A multicenter, controlled clinical trial". Ann. Intern. Med. 129 (11): 845–55. PMID 9867725[e] Online calculator at InfoRetriever
  26. Selker HP, Griffith JL, D'Agostino RB (1991). "A tool for judging coronary care unit admission appropriateness, valid for both real-time and retrospective use. A time-insensitive predictive instrument (TIPI) for acute cardiac ischemia: a multicenter study". Med Care 29 (7): 610–27. PMID 2072767[e]
  27. Selker HP et al.. Continuous monitoring using a predictive instrument. Retrieved on 2007-11-29.
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  29. Pozen MW, D'Agostino RB, Selker HP, Sytkowski PA, Hood WB (1984). "A predictive instrument to improve coronary-care-unit admission practices in acute ischemic heart disease. A prospective multicenter clinical trial.". N Engl J Med 310 (20): 1273-8. DOI:10.1056/NEJM198405173102001. PMID 6371525. Research Blogging.
  30. Christenson J, Innes G, McKnight D, Thompson CR, Wong H, Yu E et al. (2006). "A clinical prediction rule for early discharge of patients with chest pain.". Ann Emerg Med 47 (1): 1-10. DOI:10.1016/j.annemergmed.2005.08.007. PMID 16387209. Research Blogging.
  31. Braunwald E, Antman EM, Beasley JW, et al (2002). "ACC/AHA 2002 guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction--summary article: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (Committee on the Management of Patients With Unstable Angina)". J. Am. Coll. Cardiol. 40 (7): 1366–74. PMID 12383588[e]
  32. M Woollard, A Smith, and P Elwood (2001 November), Pre-hospital aspirin for suspected myocardial infarction and acute coronary syndromes: A headache for paramedics?, vol. 18, DOI:10.1136/emj.18.6.478., at 478–481
  33. Hillis LD, Lange RA (May 2009). "Optimal management of acute coronary syndromes". N. Engl. J. Med. 360 (21): 2237–40. DOI:10.1056/NEJMe0902632. PMID 19458369. Research Blogging.
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  35. Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C et al. (2009). "Ticagrelor versus clopidogrel in patients with acute coronary syndromes.". N Engl J Med 361 (11): 1045-57. DOI:10.1056/NEJMoa0904327. PMID 19717846. Research Blogging. Review in: Ann Intern Med. 2009 Dec 15;151(12):JC6-4
  36. (2010) Lancet. Comparison of ticagrelor with clopidogrel in patients with a planned invasive strategy for acute coronary syndromes (PLATO): a randomised double-blind study
  37. Giugliano RP, White JA, Bode C, et al. (May 2009). "Early versus delayed, provisional eptifibatide in acute coronary syndromes". N. Engl. J. Med. 360 (21): 2176–90. DOI:10.1056/NEJMoa0901316. Research Blogging.
  38. Cannon CP, Weintraub WS, Demopoulos LA, et al (2001). "Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban". N. Engl. J. Med. 344 (25): 1879-87. PMID 11419424[e]
  39. Bach RG, Cannon CP, Weintraub WS, et al (2004). "The effect of routine, early invasive management on outcome for elderly patients with non-ST-segment elevation acute coronary syndromes". Ann. Intern. Med. 141 (3): 186-95. PMID 15289215[e]
  40. Mehta SR, Granger CB, Boden WE, et al. (May 2009). "Early versus delayed invasive intervention in acute coronary syndromes". N. Engl. J. Med. 360 (21): 2165–75. DOI:10.1056/NEJMoa0807986. PMID 19458363. Research Blogging.
  41. Montalescot G, Cayla G, Collet JP, Elhadad S, Beygui F, Le Breton H et al. (2009). "Immediate vs delayed intervention for acute coronary syndromes: a randomized clinical trial.". JAMA 302 (9): 947-54. DOI:10.1001/jama.2009.1267. PMID 19724041. Research Blogging.
  42. de Araújo Gonçalves P, Ferreira J, Aguiar C, Seabra-Gomes R (May 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. Research Blogging.