2011 ACS Addendum Article-In-Press

8/2/2019 2011 ACS Addendum Article-In-Press

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Guideline Addendum

2011 Addendum to the National Heart Foundation ofAustralia/Cardiac Society of Australia and New

Zealand Guidelines for the Management of AcuteCoronary Syndromes (ACS) 2006

Derek P. Chew, MPH, FRACP, FACC, FCSANZa, Constantine N. Aroney, MD,FRACPb, Philip E. Aylward, FRACP, FCANZ, FRCP, FACCa, Anne-Maree Kelly, MClinEd,

FACEM, FCCPe, Harvey D. White, FRACP, FACC, FESC, FAHA, FHKCC (Hon),FCSANZc, Philip A. Tideman, FRACPd, Jill Waddell, MPHf, Leva Azadi, MPHf,

Alison J. Wilson, MBAf, and Leah-Anne M. Ruta, PhDf

a Adelaide Health Service, Flinders Medical Centre, South Australia, Australiab Holy Spirit Northside Hospital, Queensland, Australia

c Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealandd Country Health SA, Flinders Medical Centre, South Australia, Australia

e Joseph Epstein Centre for Emergency Medicine Research at Western Health, Sunshine Hospital, Victoria, AustraliafNational Heart Foundation of Australia, Victoria, Australia

Keywords. Acute coronary syndromes; STEMI; NSTEACS

About This Addendum

This addendum summarises clinical trial evidencepublished since 2007 that is relevant to the rec-ommendations contained in the Heart FoundationsGuidelines for the management of acute coronary syndromes

2006 [1](2006Guidelines)and2007addendumtotheNationalHeart Foundation of Australia/Cardiac Society of Australia andNew Zealand Guidelines for the management of acute coronarysyndromes 2006 [2] (2007 Addendum). These recommen-dations are directed at the management of patients withspontaneous acutecoronary syndromes, rather thanthoseoccurring as a result of other conditions (e.g. anaemia orthyrotoxicosis) where management may be directed at theunderlying cause.

Grades of recommendation and levels of evidence areindicated according to current National Health and Medi-cal Research Council classifications (Tables 1 and 2) [3]. Inaddition, consensus recommendations have been madewhere there is insufficient evidence on which to base a

grading.When applying this information, clinicians should con-

sider the context and circumstances of the individualpatient and the clinical setting.

Received 28 February 2011; accepted 7 March 2011

Corresponding author. Tel.: +61 393211524.E-mail address: [email protected](L.-A.M. Ruta).

Investigations: Serum Troponin Measurement(2006 Guidelines Pages S12S13)

Important Recent Findings

EARLY DETECTION OF MYOCARDIAL INFARCTION. New improvedassays of cardiac troponins T (TnT) and I (TnI) show

acceptable analytical precision at levels 10- to 100-foldlower thanconventionalassays.Thesuperiorperformanceof these high sensitivity assays for early detection ofmyocardial infarction (MI) has been confirmed in largeclinical trials [46].

A study of 1818 consecutive patients with chest painreported thata single testat presentation to the emergencydepartment (ED) was highly accurate for the diagnosis ofMI (area under the receiver-operating-characteristic curve[AUC] 0.96) when using a sensitive TnI assays, comparedwith conventional assays (AUC 0.85) [5].

A studyin patientswith a confirmeddiagnosis ofnon-STelevation myocardial infarction (NSTEMI) demonstratedthat serial sampling using a high sensitivity TnT assay

enabled possible earlier diagnosis. Amongst patients witha negative test on admission using conventional fourth-generation TnT testing, two-thirds tested positive on thehigh sensitivity test. Compared with the conventionalassay, the high sensitivity assay identified 20% morepatients with a final diagnosis of NSTEMI [7].

SENSITIVITY AND SPECIFICITY. The new high sensitivity assaysachieve increased sensitivity in early diagnosis at the costof reduced specificity [5,6,8,9]. The cumulative sensitivityof a sensitive TnI for the diagnosis of acute MI, using a

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2 Chew et al. Heart, Lung and Circulation2011 Addendum to the National Heart Foundation of Australia/Cardiac Society of Australia and New Zealand Guidelines for the Management

of Acute Coronary Syndromes (ACS) 2006 2011;xxx:116

Table 1. Summary of Recommendations.

Recommendation Grade Level

Investigations: serum troponin measurementWhere available, high sensitivity troponin assays should be used in preference toconventional assays.

N/A N/A

When using high sensitivity troponin assay, a test should be interpreted as positive iflevel is 99th centile for reference population OR there is a change of >50% above aninitial baseline level. A positive finding should be followed up by a search for analternative plausible diagnosis and/or cardiac consultation if ACS is suspected.

Consensus N/A

At 3 hours after presentation (with at least one assay performed >6 hours fromsymptom onset), a test using a high sensitivity troponin assay should be interpreted asnegative if the level is


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Heart, Lung and Circulation Chew et al. 32011;xxx:116 2011 Addendum to the National Heart Foundation of Australia/Cardiac Society of Australia and New Zealand Guidelines for the

Management of Acute Coronary Syndromes (ACS) 2006

Table 1 (Continued).

Recommendation Grade Level

peripheral vascular disease anaemia concomitant use of a GP IIb/IIIa inhibitor administration of enoxaparin 48 hours prior to intervention switching between UF heparin and enoxaparin procedural factors associated with increased risk (femoral artery versus radial artery

access, prolonged procedure, intra-aortic balloon pulsation, right heart catheterisation). low body weight 20% increase from baseline troponin suggestsevolving MI, whilst a 20% decrease suggests resolving

MI [13]. Accordingly, recent consensus guidelines [1315]recommend that, in patients who present with ischaemic

Table 3. Elevations of Troponin in the Absence of OvertIschaemic Heart Disease [12].

Cardiac contusion, or other trauma including surgery,ablation, pacing, etc.

Congestive heart failureacute and chronic Aortic dissection Aortic valve disease Hypertrophic cardiomyopathy Tachy- or bradyarrhythmias, or heart block Apical ballooning syndrome Rhabdomyolysis with cardiac injury Pulmonary embolism, severe pulmonary hypertension Renal failure Acute neurological disease, including stroke or subarachnoid

haemorrhage Infiltrative diseases, e.g. amyloidosis, haemochromatosis,

sarcoidosis, and scleroderma Inflammatory diseases, e.g. myocarditis or myocardial

extension of endo-/pericarditis Drug toxicity or toxins Critically ill patients, especially with respiratory failure or

sepsis Burns, especially if affecting >30% of body surface area Extreme exertion


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symptoms or electrocardiogram (ECG) changes, the diag-nosis of MI requires both an elevation of troponin levelsabove the 99th centile and a >20% change (rise and/or fall)in troponin level when using older troponin assays.

However, a recent study in healthy individuals demon-strated intra-individual variation of 46% between samples

taken hours or weeks apart [16]. Therefore, the minimumchangeintroponinlevelsthatrepresentsaclinicallymean-ingful finding may actually be greater than the 20% citedin current guidelines. Hence, clear documentation of thetype of troponin assay being used is necessary.

Diagnosticthresholds have not yet beendefined accord-ing to outcome data andthereare currentlyno data clearlydemonstrating the amount of change between serialassays that accurately identifies MI and balances sensitiv-ity and specificity. Nevertheless, a rising troponin level onserialtesting suggests that evolvingMI or other significantpathology cannot be excluded and further investigationsmay be required. Confirmation of the diagnosis of MIwill often require troponin interpretation in the contextof entire clinical presentation and additional cardiac tests.The finding of stable troponin concentrations (e.g. nochange during a period of more than 24 hours) suggeststhat the presence of troponin is due to chronic diseasesuch as renal failure, heart failure, sepsis or myocarditis.These guidelines will be updated when further informa-tion regarding the link between serial troponin testing andoutcomes are established.

RECOMMENDED PROTOCOL FOR TROPONIN TESTING USING HIGH

SENSITIVITY ASSAYS IN RULING-OUT ACS. All patients with asuspected ACS should undergo troponin testing on arrivalat ED to rule in ACS within the differential diagnosis(Fig. 1):

For a patient with a positive troponin result or a changein troponin levels over time, neither ACS nor othersignificant pathology (e.g. pulmonary embolus, aorticdissection, and sepsis, see Table 3) can be excluded.These patients are at higher risk of subsequent events.A positive result should be considered within the entireclinical context (history, examination, ECG findings andother investigations). Further investigations directed atall plausible clinical diagnoses should be consideredand, if ACS is thought to be the likely cause, thesepatients may require cardiology assessment.

All patients with a negative result should undergorepeat testing 34hours later.

The testing interval to rule out MI may be reduced to

3 hours, provided that one sample is taken at least 6hoursafter symptom onset:

Patients with a negative result at 3 hours after presenta-tion and at least 6 hours after the onset of pain shouldbe considered for early assessment by non-invasiveanatomic or functional testing, as determined by localavailability.

For patients presenting more than 6 hours after painonset, a single high sensitivity troponin assay is suffi-cient to rule out myocardial infarction.

Implications of the FindingsPrevious recommendationsThe 2006 Guidelines advised that serum troponinlevels be measured on admission to the ED. This rec-ommendation still applies.

The 2006 Guidelines recommended that, if the ini-tial troponin test is negative, it should be repeatedat least 8 hours after the last episode of pain or othersymptoms of coronary insufficiency. (When used inthis way, troponin assays have a high sensitivity fordetecting MI, but levels may be normal in other pre-sentations of ACS.)This recommendationstill applieswhen using standard-sensitivity troponin assays.New recommendations

1. Where available, high sensitivity troponin assaysshould be used in preference to conventionalassays. [Grade of recommendation N/A]

2. When using high sensitivity troponin assays forthe identification of patients at increased risk (see

Recommended protocol): A test should be interpreted as positive if level

is 99th centile for reference population ORthere is a change of >50% above an initial base-line level. A positive finding identifies patientsat increased risk, but does not provide defini-tive evidence of MI. A positive troponin resultshould be followed up by a search for analternative plausible diagnosis and/or cardiacconsultation if ACS is suspected in the contextof the clinical presentation. [Consensus recom-mendation]

At 3 hours after presentation, a test should beinterpreted as negative if level is 50% above an initial baseline level) shouldbe interpreted in the context of the entire clinical presen-tation and does not necessarily represent an indicationfor coronary angiography. In addition to the alterna-tive diagnoses presented in Table 3, the management MIsecondary to other conditions (e.g. anaemia, thyrotoxi-


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Figure 1. Algorithm for incorporating a high sensitivity troponin into the work-up of patients with suspected acute coronary syndromes (ACS).

cosis, and sepsis) should be primarily directed at thoseconditions.

The finding of troponin concentrations that remain sta-ble over time suggests that thepresence of troponin is dueto chronic disease. Acute exacerbations of chronic diseasethat result in elevated troponin levels can mimic an MIrelease pattern [16].

Choice of Reperfusion Therapy for STEMI (2006Guidelines Pages S14S20)


REPERFUSION STRATEGY. Accumulating evidence supportsreduction in delays to primary percutaneous coronaryintervention (PCI) for patients with ST-elevation MI


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(STEMI) through ambulance triage and early activationof the catheterisation laboratory. Several recent studiessupport the implementation of a pharmaco-invasive strat-egyfor patients presenting to centres without primary PCIcapacity. In patients with STEMI and high risk featuresincluding extensive elevation, or Killip class 2, treat-

ment with fibrinolysis, followed by routine early coronaryangiography and PCI with intra-procedural glycoprotein(GP) IIb/IIIa inhibition, was associated with reductionsin the combined endpoint of recurrent MI and recurrentischaemia andthe combined endpoint of death andrecur-rent MI, but not mortality alone, compared with standardtreatment in the NORDICSTEMI,1 CARESS-AMI2 andTRANSFER-AMI3 studies [1720]. Overall, no increase inmajor bleeding or stroke was seen.

Emerging data suggest superior outcomes for primaryPCI compared with fibrinolysis amongst the very elderly.In the relatively small TRIANA4 study in patients withSTEMI aged more than 80 years in whom reperfusion wasconsidered appropriate, primary PCI was associated witha lower rate of the combined endpoint of death, MI andstroke, but not mortality alone, compared with fibrinolysis[21].

MODIFICATIONS TO PRIMARY PCI TECHNIQUE. Data from theHORIZONS-AMI5 randomised trial and large SwedishCoronary Angiography and Angioplasty Registry(SCAAR) do not confirm that the use of drug-elutingstents is associated with an increased risk of late clinicalevents within the context of primary PCI for STEMI[22,23].

Accumulating evidence supports the use of mechan-ical thrombectomy techniques prior to balloon inflationand stent placement in patients undergoing primary PCI.A recent meta-analysis of eleven trials comparing stan-

dard PCI with or without thrombectomy found that thosereceiving thrombectomy experienced a significantly lowerrate of death and recurrent MI [24].

Antithrombotic Therapy for STEMI (2006Guidelines Page S14, 2007 Addendum Pages302303)


BIVALIRUDIN. The HORIZONS-AMI study in patients withSTEMI undergoing PCI found that anticoagulation withbivalirudin was associated with a reduction in majorbleeding events, compared with heparin plus GP IIb/IIIainhibition [25]. A reduction in 30-day mortality was also

seen in the bivalirudin group compared with the group

1 Norwegian Studyon District Treatment of ST-elevationMyocar-dial Infarction.2 Combined Abciximab Reteplase Stent Study in Acute Myocar-dial Infarction.3 Trial of Routine Angioplasty and Stenting after Fibrinolysis toEnhance Reperfusion in Acute Myocardial Infarction.4 Thrombolysis Versus Primary Angioplasty for AMI in ElderlyPatients.5 Harmonizing Outcomes with Revascularization and Stents inAcute Myocardial Infarction.

Implications of the FindingsPrevious recommendationsThe 2006 Guidelines indicated that undertakingimmediate PCI after full-dose fibrinolysis, regardlessof reperfusion status (also known as facilitated PCI)

could not be recommended at the time of writing.New recommendations

1. Consider early routine angiography and revascu-larisation amongst patients receiving fibrinolysis,regardless of the success of pharmacologic reper-fusion. [Grade A recommendation, Evidence levelI]

2. Antiplatelet therapies should be continued for 12months for all stented patients. [Grade A recom-mendation, Evidence level II]

3. The use of mechanical thrombectomy techniquesto reduce thrombus burden during primary PCIshould be considered. [Grade A recommendation,Evidence level I]

receiving heparin plus GP IIb/IIIa inhibition (2.1% versus3.1%, P =0.048) [25].

However, a small increase in early (24hours) stentthrombosis was observed in the bivalirudin group [25],indicating the need for early initiation of high-doseantiplatelet therapy and highlighting a potential role formore potent oral agents (see below). These data reinforcetheneedfor thorough consideration of bleeding risk whenconsidering pharmacotherapy options amongst patientsundergoing primary PCI.

EARLY ANTITHROMBOTICTHERAPY. Amongst patients undergo-ing cardiac catheterisation procedures, there is accumu-lating evidence that those who commence GP IIb/IIIainhibition prior to transfer to the catheterisation labora-tory show improved angiographic outcomes at the time ofthe procedure. In the On-TIME 26 study in patients withSTEMI undergoing primary PCI, early antithrombotictherapy was also associated with reductions in all-causemortality at 12 month follow-up [26].

CARDIOGENIC SHOCK AND CARDIAC ARREST. In the PRAGUE-77 study, the administration of GP IIb/IIIa inhibitionwas of little benefit in patients with cardiogenic shock[27]. Similarly, amongst patients in cardiac arrest, throm-

bolytic therapy is not associated with improved outcomes[28]. However, amongst patients with resuscitated car-diac arrest, where there is evidence of ST-elevation ornew bundle branch block, emergent reperfusion shouldbe considered [28].

6 Ongoing Tirofiban In Myocardial Infarction Evaluation 2.7 Routine Upfront Abciximab Versus Standard Peri-ProceduralTherapy in Patients Undergoing Percutaneous Coronary Inter-vention for Cardiogenic Shock.


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PRASUGREL AND TICAGRELOR. The Triton-TIMI 38 studyreported that, compared with clopidogrel, prasugrel wasassociated with a reduction in the combined endpoint ofcardiovascular death, MI or stroke in patients with ACSscheduled for PCI, but at the cost of an increase in therate of major bleeding [33]. Similarly, in thePLATO trial in

patients admitted to hospital with ACS with or without STelevation, ticagrelor was associated with a reduction in thecomposite endpoint of cardiovascular death, MI or strokeat 12 months, compared with clopidogrel [32]. However,theticagrelorgroupshowedhigherratesofmajorbleedingnot related to the coronary artery bypass graft procedure,which included cases of fatal intracranial bleeding [32].15

ENOXAPARIN. The SYNERGY16 study reported that, com-pared with UF heparin, enoxaparin was associated withan increased rate of thrombolysis in myocardial infarction(TIMI) major bleeding amongst patients with high-riskNSTEACS [39].

Cross-over between enoxaparin and UF heparin wasassociatedwith increasedbleedingin the SYNERGYstudy

[39]. Crossover from heparin or enoxaparin to bivalirudinwas associated with lower rates of bleeding than uninter-rupted treatment with combined heparin and GP IIb/IIIainhibitor in the ACUITY study [40].

DOSING ERRORS. Data from the CRUSADE17 study demon-strated that dosing errors with antithrombotic agents aremost common in the elderly, women and patients withchronic kidney disease. Failure to correct for weight andrenalfunctionmayaccountfor 15% ofcasesof majorbleed-ing in patients with NSTEACS [41].

Implications of the FindingsPrevious recommendations

The 2006 Guidelines recommended use of heparinor subcutaneous enoxaparin until angiography, orfor 4872 hours, for those with high-risk NSTEACS.The 2007 addendum indicated that fondaparinuxand/or bivalirudin (both of which were then unli-censed for upstream therapy for NSTEACS), may bepreferable alternatives to standard therapy with UFheparin or low-molecular-weight heparin (LMWH)with a GP IIb/IIIa inhibitorfor patients with high-riskNSTEACS, particularly in patients with an increasedrisk of bleeding.

15 Useof long-acting potent antiplatelet agents(clopiodgrel, pra-sugrel and possibly ticagrelor) before the coronary anatomy hasbeen defined should be weighed against the possible need forurgent CABG. Prediction of NSTEACS patients who will likelyrequire urgent CABG is difficult, and strongly influenced by localpractices.16 Superior Yield of the New strategy of Enoxaparin, Revascular-ization, and Glycoprotein IIb/IIIa inhibitors.17 Can Rapid Risk Stratification of Unstable Angina PatientsSuppress Adverse Outcomes with Early Implementation of theACC/AHA Guidelines.

New recommendationsA newparadigm forthe management of patients withhigh-risk NSTEACS is now recommended. Man-agement decisions must take into consideration thebalance between ischaemic and bleeding risk for the

individual patient.1. For all patients with high-risk NSTEACS, consider

methods to reduce bleeding risk. [GradeA recom-mendation, Evidence level I] Titrateantithromboticagentstooptimaldosefor

weight and renalfunction. [Grade A recommen-dation, Evidence level I]

Avoid upstream GP IIb/IIIa inhibitors unlessthere is recurrent ischaemia on standardmedical therapy. [Grade B recommendation,Evidence level II]

Consider radial access in preference to femoralaccess for PCI, but be mindful that this may beused as a conduit for surgery (CABG). [Grade B

recommendation, Evidence level III] During PCI, avoid right heart catheterisation

and intra-aortic balloon pulsation unless indi-cated, and avoid prolonged procedure times.[Grade C recommendation, Evidence level III]

2. For all patients with high-risk NSTEACS, assessbleedingriskindividually accordingto thenumberand severity of bleeding risk factors (see Bleedingrisk in ACS). [Grade A recommendation, Evidencelevel II]

3. Assign a management strategy according toassessed individual bleeding risk:

Use a standard strategy for patients at low riskof bleeding:

Choose the most effective anti-platelet regimen(e.g. prasugrel or ticagrelor). [Grade A recom-mendation,EvidencelevelI], anduse fast-actingagentsor multiple agents, asrequired, to controlischaemia rapidly. [Grade B recommendation,Evidence level II]

Use a priority low-bleeding strategy in patients athigh risk of bleeding:

Use antithrombotic agents with a lower bleedingrisk, e.g.: clopidogrel in preference to prasugrel. [Grade B

recommendation, Evidence level II] (in the context of a non-invasive strategy) fonda-

parinux in preference to enoxaparin. [Grade Brecommendation, Evidence level II] (inthe context of an invasive strategy)bivalirudin

in preference to enoxaparin. [Grade B recom-mendation, Evidence level II]

Minimise the number of agents used. [Grade Brecommendation, Evidence level II]

When additional agents are needed, considersubstituting rather than adding them. [Grade Brecommendation, Evidence level II]


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(Continued)

Consider shorter-acting or reversible agents, e.g.bivalirudin. [Grade B recommendation, Evidencelevel II]

Avoid the use of GP IIb/IIIa inhibitors, if possible.

[Grade B recommendation, Evidence level II]

Bleeding Risk in ACS (2006 Guidelines Pages S14,S16, S1819)


BLEEDING AND PROGNOSIS. Reducing bleeding has beenshown to improve outcomes for patients with ACS andreduce costs.Major bleedingoccurs in approximately4.8%of patients with STEMI,4.7% of patients with NSTEMI and2.3% of patients with unstable angina [42]. It is associatedwith increased in-hospital mortality (estimated rates of7.022.8% in patients with STEMI, 5.315.3% in patientswith NSTEMI and 3.016.1% in patients with unstableangina). Major bleeding [43,44] and transfusion [45] areboth strong predictors of mortality in ACS patients andare associated with an increase in risk that is comparableto recurrent myocardial infarction.

Table 4. Integer-Based Risk Score for NonCABG-Related Major Bleeding Within 30 Days of Patient Presentation With AcuteCoronary Syndrome [51].

Gender Add to score Total Score Non-CABG major bleeding within 30 days (%)

Male 0 0 0.9Female 8 5 1.6

Age (years) 10 2.8< 50 0 15 4.750-59 3 20 7.9

60-69 6 25 12.970-79 9 30 20.4 80 12 35 30.7Serum creatinine (mg/dl) 40 43.5< 1.0 01.0- 21.2- 31.4- 51.6- 61.8- 8 2.0 10White blood cell count (giga/l)< 10 010- 212- 314- 516- 618- 8 20 10

AnaemiaNo 0

Yes 6PresentationSTEMI + 6NSTEMI raised biomarkers + 2NSTEMI normal biomarkers 0

Antithrombotic medicationsHeparin plus a GPI 0Bivalirudin monotherapy -5

*If patient is on bivalirudin alone rather than heparin plus glycoprotein IIb/IIIa inhibitor (GPI), the total score should be reduced by 5.

FACTORS ASSOCIATED WITH BLEEDING RISK. Older age, femalesex, renal insufficiency, history of bleeding, right heartcatheterisation and use of GPIIb/IIIa inhibitorswere iden-tified as independent risk factors for major bleedingin patients with ACS in the large Global Registry ofAcute Coronary Events (GRACE) database [42]. Anaemia,

creatinine clearance


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10 Chew et al. Heart, Lung and Circulation2011 Addendum to theNationalHeart Foundation of Australia/Cardiac Society of Australiaand NewZealand Guidelines for theManagement


Table 5. GRACE risk score for acute coronary syndromes (0258) [12].

Points Total points Probability of in-hospital death (%)

Age (years)< 40 0 60 0.24049 18 70 0.35059 36 80 0.46069 55 90 0.67079 73 100 0.8 80 91 110 1.1

Heart rate (beats per min) 120 1.6< 70 0 130 2.17089 7 140 2.990109 13 150 3.9110149 23 160 5.4150199 36 170 7.3> 200 46 180 9.8

Systolic blood pressure (mm Hg)< 80 63 190 138099 58 200 18100119 47 210 23120139 37 220 29140159 26 230 36160199 11 240 44

> 200 0 250 52Creatinine (mol/L)

034 23570 571105 8106140 11141176 14177353 23 354 31

Killip classClass I 0Class II 21Class III 43Class IV 64

Other risk factorsCardiac arrest at admission 43

Elevated cardiac markers 15ST segment deviation 30

mated glomerular filtration rate (eGFR), pre-existinganaemia, anduse of LMWH within48 hours prior to PCI[49].

A risk score for predicting bleeding in patientswith NSTEACS, based on independent risk factorsidentifiedin theCRUSADE registry data, includes crea-tinine clearance rate, anaemia, female sex, tachycardia,hypotension or severe hypertension, heart failure, dia-betes and peripheral vascular disease [50].

The use of clinical risk scores for both recurrentischaemic events and bleeding events may assist in theindividualisation of pharmacotherapies amongst patientswith additional co-morbidities. Details of the GRACE riskscore for recurrent ischaemic events and risk score forbleeding events derived from recent ACS trials are pre-sented in Tables 4 and 5.

18 Randomized Evaluation in PCI Linking Angiomax to ReducedClinical Events.

Oxygen Therapy for Patients with ACS (2006Guidelines Pages S7, S1112)

Important recent findings

Recent analyses have raised questions about the role ofroutine oxygen therapy within the first 24 hours of treat-ment for acute MI. A recent Cochrane meta-analysis [52]examining this question identified three trials with a totalof 387 patients in whom 14 deaths occurred. The relativerisk of death for those receiving oxygen therapy was 2.88(95% CI 0.889.39) by intention-to-treat analysis and 3.03

(95% CI 0.939.83) amongst patients with confirmed acuteMI. Whilst these findings suggest increased hazard, theanalyses lacked adequate power to address the risks andbenefits of oxygen therapy in acute MI. There is currentlyinsufficient evidence to formulate clear recommendationsabout oxygen therapy [52]. Definitive trials are needed toanswer this question.

There is a lack of evidence to support the routine useof oxygen therapy in patients presenting with potential orconfirmed ACS. However, there is some evidence suggest-ing it may be harmful.


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Implications of the FindingsPrevious recommendationsThe2006 Guidelinesspecify the followingcontraindi-cations to fibrinolysis based on bleeding risk:

full-dose GP IIb/IIIa inhibitors with fibrinolytic

therapy, particularly in the elderly active bleeding or bleeding diathesis (excluding

menses) significant closed head or facial trauma within

3 months suspected aortic dissection (including new neuro-

logical symptoms) current use of anticoagulants (risk of bleeding is

positively correlatedwith international normalisedratio)

non-compressible vascular punctures recent major surgery (10 min)cardiopulmonary

resuscitation

recent (within 4 weeks) internal bleeding (forexample, gastrointestinal or urinary tract haemor-rhage)

active peptic ulcer.

These contraindications still apply in addition to newrecommendations.New recommendations

1. The following risk factors should be consideredwhen assessing bleeding risk and when choosinganti-thrombotic therapies in patients with ACS:[Grade B recommendation, Evidence level II] age >75 years female sex

history of bleeding history of stroke or TIA creatinine clearance rate


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Table 6. Adjusted Associations Between Hospital Strategies and Door-to-Balloon Times [58]*.

Strategy Door-to-Balloon Time (95% CI) (min) P value Wald P Value

Catheterisation laboratory is activated byemergency medicine physician

0.01

NoYes 8.2 (14.3 to 2.0) 0.01

Process for activating catheterisation team 0.01After communicating with the emergency

department, interventional cardiologistactivates catheterisation laboratory by callingstaff or a central page operator

Emergency department makes at least twocalls: one to the interventional cardiologistand another to a central page operator, whopages catheterisation laboratory staff

6.8 (12.5 to 1.0) 0.03

Emergency department makes a single call to acentral page operator, who then pagesinterventional cardiologist andcatheterisation laboratory staff

13.8 (21.2 to 6.4) 0.001

No standard approach 13.2 (37.8 to 64.2) 0.66Other 5.0 (14.1 to 4.0) 0.28

Process after emergency medical servicetransmits ECG results

0.004

Emergency department waits for patient toarrive at the hospital to determine whethercatheterisation laboratory should beactivated

Emergency department contacts cardiologistwhilst the patient is en route to determinewhether catheterisation laboratory should beactivated

8.9 (17.8 to 0) 0.06

Emergency department activatescatheterisation laboratory whilst the patientis still en route to the hospital

15.4 (24.2 to 6.6)a 0.001

No set protocol or variable protocol 23.2 (35.3 to 11.1)b 0.001Not applicable because ECG data not

transmitted to emergency department6.6 (15.2 to 2.1) 0.14

Not applicable because ECG never performeden route

4.3 (12.0 to 3.3) 0.27

Unknown or no response 5.6 (13.3 to 2.2) 0.17

Expected interval between page and arrival ofstaff in catheterisation laboratory

0.01

20min2130 min 3.5 (4.6 to 11.6)c 0.40>30 min 19.3 (6.0 to 32.7) 0.002No expected time 8.8 (0.7 to 18.3) 0.06

An attending cardiologist is always at the hospital 0.01No

Yes 14.6 (25.7 to 3.6) 0.01

Hospital gives real-time feedback to staff inemergency department and catheterisationlaboratory

0.001

NoYes 8.6 (13.6 to 3.6) 0.001

aP = 0.01 for the comparison with the door-to-balloon time at hospitals reporting that electrocardiography was never performed en route by emergency

medical services.bP = 0.01 for the comparison with the door-to-balloon time at hospitals reporting that emergency medical services never called in or transmittedelectrocardiographic data. Hospitals that reported having no set protocol or a variable protocol could have used a variety of strategies, including

activation of the catheterisation laboratory before the patient arrived, for expediting the door-to-balloon time.cP = 0.003 for the comparison with the door-to-balloon time at hospitals with an expected interval of more than 30min. All variables are centred at their mean value; therefore, the changes in minutes are relative to those of hospitals with an average score on all other

items. CI denotes confidence interval, and ECG electrocardiography. The reference category is the first listed response to each question.P values were calculated with the use of the Wald chi-square test.


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Implications of the FindingsTimely reperfusion remains a keytreatment objectivein the management of STEMI.Previous recommendationsThe 2006 Guidelines stated that local approaches to

reperfusion depend on the specific local resourcesavailable for assessment, transfer and delivery ofcare.New recommendations

1. System-based approaches to deliver timely reper-fusion should be undertaken at local level.Establishment of clinical networks and efficientprotocols to maximise the proportion of patientsreceiving timely reperfusion should be consid-ered. [Grade B recommendation; Evidence levelIII-1]

2. Routine audit should be integrated into all clinicalservices that provide care to patients with ACS.[Grade B recommendation; Evidence level III].

3. In the absence of ready access to primary PCI ser-vices, systems should be developed to train localgeneral practitioners and other health workersto initiate fibrinolysis in patients with STEMI, tomaintain practitioners skills, and to ensure prac-titioners are supported by ready access to expertcardiology consultation. [Recommendation gradeN/A]

Measures of performance such as door-to-balloon time,door-to-needle time and the prescription of secondaryprevention therapies have been established internation-ally and locally.

Conflicts of interest

Derek Chew has received travel assistance, speaker feesor been on the advisory board for Astra Zeneca Australia,

Eli-Lilly Australia and Sanofi Aventis Australia. ConAroney has received travel assistance from BoehringerIngelheim. Philip Aylward has received research hon-oraria, research grants, travel assistance or been onadvisory boards for Boehringer Ingelheim, Astra Zeneca,Eli-Lilly, CSL, Merck Sharp & Dohme, Pfizer, SanofiAventis. Philip Tideman has received speakers hono-raria from Roche Diagnostics Australia. Harvey White hasreceived research grants from Sanofi Aventis, Eli-Lilly,The Medicines Company, National Institutes of Health,Pfizer, Roche, Johnson & Johnson, ScheringPlough, MerckSharp & Dohme, Astra Zeneca, Daiichi Sankyo PharmaDevelopment, Bristol-Myers Squibb and consulting feesfrom Regado Biosciences. Anne-Maree Kelly is a mem-ber of advisory boards to Astra Zeneca and MerckSharp & Dohme and has received travel assistance fromRadiometer Pty Ltd, is the Senior Clinical Advisor forthe Emergency Care Improvement and Innovation Clin-ical Network (Department of Health Victoria), is on theeditorial boards ofEmergency Medicine Australasia, Annalsof Emergency Medicine and Hong Kong Journal of EmergencyMedicine and conducts research in acute cardiology andbiomarkers.


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Appendix A.

A1. NHMRC Evidence Hierarchy.a

Level Intervention Diagnostic Accuracy Prognosis Aetiology Screening Intervention

I A systematic review of level II studies

A systematic review oflevel II studies


A systematicreview of level IIstudies


II A randomisedcontrolled trial

A study of testaccuracy with: anindependent, blindedcomparison with avalid referencestandard, amongstconsecutive personswith a defined clinicalpresentation

A prospective cohortstudy

A prospectivecohort study

A randomisedcontrolled trial

III-1 A pseudo-randomisedcontrolled trial (i.e.alternate allocation orsome other method)

A study of testaccuracy with: anindependent, blindedcomparison with avalid referencestandard, amongstnon-consecutivepersons with a defined

clinical presentation

All or none All or none A pseudo-randomisedcontrolled trial (i.e.alternate allocation orsome other method)

III-2 A comparative studywith concurrentcontrols: Non-randomised,experimental trial Cohort study Casecontrol study Interrupted time serieswith a control group

A comparison withreference standardthat does not meet thecriteria required forlevel II and III-1evidence

Analysis of prognosticfactors amongstpersons in a single armof a randomisedcontrolled trial

A retrospectivecohort study

A comparative studywith concurrentcontrols: Non-randomised,experimental trial Cohort study Casecontrol study

III-3 A comparative studywithout concurrentcontrols: Historical controlstudy Two or more singlearm study

Interrupted timeseries without aparallel control group

Diagnosticcasecontrol study

A retrospective cohortstudy

A casecontrolstudy

A comparative studywithout concurrentcontrols: Historical controlstudy Two or more singlearm study

IV Case series with eitherpost-test orpre-test/post-testoutcomes

Study of diagnosticyield (no referencestandard)

Case series, or cohortstudy of persons atdifferent stages ofdisease

Across-sectionalstudy or caseseries

Case series

a For all references and explanatory notes, see Ref. [3].

References

[1] Acute Coronary Syndrome Guidelines Working Group.Guidelines for the management of acute coronary syn-dromes 2006. Med J Aust 2006;184(8 Suppl.):S132.

[2] Aroney CN, Ayward P, Chew DP, Huang N, Kelly A, White

H, et al. 2007 addendum to the National Heart Foundationof Australia/Cardiac Society of Australia and New ZealandGuidelines for the management of acute coronary syn-dromes 2006. Med J Aust 2008;188:3023.

[3] National Health and Medical Research Council. Levelsof evidence and grades for recommendations for devel-opers of guidelines. Canberra: NHMRC; 2009. Availableat http://www.nhmrc.gov.au/ files nhmrc/file/guidelines/evidence statement form.pdf [last accessed December2010].

[4] Apple FS. A new season for cardiac troponin assays: its timeto keep a scorecard. Clin Chem 2009;55(7):13036.

[5] KellerT, ZellerT, PeetzD, TzikasS, RothA, CzyzE, etal. Sen-sitive troponin I assay in early diagnosis of acute myocardialinfarction. N Engl J Med 2009;361(9):86877.

[6] Reichlin T, Hochholzer W, Bassetti S, Steuer S, Stelzig C,Hartwiger S, et al. Early diagnosis of myocardial infarc-tion with sensitive cardiac troponin assays. N Engl J Med

2009;361(9):85867.[7] Giannitsis E, Kurz K, Hallermayer K, Jarausch J, Jaffe AS,Katus HA. Analytical validation of a high-sensitivity cardiactroponin T assay. Clin Chem 2010;56(2):25461.

[8] Eggers KM, OldgrenJ, Nordenskjld A, Lindahl B. Diagnos-ticvalue ofserialmeasurementof cardiac markers inpatientswith chest pain: limited value of adding myoglobin to tro-ponin I for exclusion of myocardial infarction. Am Heart J2004;148(4):57481.

[9] MacRae AR, Kavsak PA, LustigV, Bhargava R, Vandersluis R,PalomakiGE, et al. Assessing the requirement for the 6-hourinterval between specimens in the American Heart Associa-
http://www.nhmrc.gov.au/_files_nhmrc/file/guidelines/evidence_statement_form.pdfhttp://www.nhmrc.gov.au/_files_nhmrc/file/guidelines/evidence_statement_form.pdfhttp://www.nhmrc.gov.au/_files_nhmrc/file/guidelines/evidence_statement_form.pdfhttp://www.nhmrc.gov.au/_files_nhmrc/file/guidelines/evidence_statement_form.pdf


15/16

ARTICLE IN PRESS

GUIDELINE



tion Classification of myocardial infarction in epidemiologyand clinical research studies. Clin Chem 2006;52(5):8128.

[10] Jeremias A, Gibson CM. Narrative review: alternative causesfor elevatedcardiactroponin levels whenacute coronary syn-dromes are excluded. Ann Intern Med 2005;142(9):78691.

[11] Jaffe AS, Apple FS. High-sensitivity cardiac troponin: hype,help, and reality. Clin Chem 2010;56(3):3424.

[12] White HD,Chew DP. Acutemyocardialinfarction.The Lancet2008;372:57084.

[13] Morrow DA, Cannon CP, Jesse RL, Newby LK, Ravkilde J,StorrowAB, et al. National Academy of Clinical BiochemistryLaboratory Medicine practice guidelines: clinical charac-teristics and utilization of biochemical markers in acutecoronary syndromes. Clin Chem 2007;53(4):52274.

[14] Thygesen K, Alpert JS, White HD, Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarc-tion. Universal definition of myocardialinfarction. Eur Heart

J 2007;28(20):252538.[15] Gibler WB, Cannon CP, Blomkalns AL, Char DM, Drew

BJ, Hollander JE, et al. Practical implementation of theguidelines for unstable angina/non-ST-segment elevationmyocardial infarction in the emergency department. AnnEmerg Med 2005;46(2):18597.

[16] Wu AH, Lu QA, Todd J, Moecks J, Wians F. Short-and long-termbiological variationin cardiac troponin I measured witha high-sensitivity assay: implications for clinical practice.Clin Chem 2009;55(1):528.

[17] BhmerE, Hoffmann P, AbdelnoorM, ArnesenH, HalvorsenS. Efficacy and safety of immediate angioplasty versusischemia-guided management after thrombolysis in acutemyocardial infarction in areas with very long transfer dis-tances results of the NORDISTEMI (NORwegian study onDIstrict treatment of ST-elevation myocardial infarction). JAm Coll Cardiol 2010;33(2):10210.

[18] Di Mario C, Dudek D, Piscione F, Mielecki W, Savonitto S,MurenaE, et al. Immediate angioplastyversus standard ther-apy with rescue angioplasty after thrombolysis in the Com-bined Abciximab REteplase Stent Studyin AcuteMyocardial

Infarction (CARESS-in-AMI): an open, prospective, ran-domised, multicentre trial. Lancet 2008;371(9612):55968.

[19] Cantor WJ, Fitchett D, Borgundvaag B, Ducas J, Heffer-nan M, Cohen EA, et al. Routine early angioplasty afterfibrinolysis for acute myocardial infarction. N Engl J Med2009;360(26):270518.

[20] Borgia F, Goodman SG, Halvorsen S, Cantor WJ, Piscione F,Le May MR,et al.Early routinepercutaneous coronary inter-vention after fibrinolysis vs. standard therapy in ST-segmentelevationmyocardial infarction: a meta-analysis. Eur Heart J2010;31(17):215669.

[21] Bueno H, Alonso JJ, Amadeo B, Cequier A, Garcia EJ, HerasM, et al. Primary angioplasty versus fibrinolysis in the veryelderly. In: The TRIANA study in ESC congress 2009. Euro-pean Society of Cardiology; 2009.

[22] Stone GW, Lansky AJ, Pocock SJ, Gersh BJ, Dangas G,

Wong SC, et al. Paclitaxel-eluting stents versus bare-metal stents in acute myocardial infarction. N Engl J Med2009;360(19):194659.

[23] James SK, Stenestrand U, Lindbck J, Carlsson J, ScherstnF, Nilsson T, et al. Long-term safety and efficacy of drug-eluting versus bare-metal stents in Sweden. N Engl J Med2009;360(19):193345.

[24] Burzotta F, De Vita M, Gu YL, Isshiki T, Lefvre T,Kaltoft A, et al. Clinical impact of thrombectomy in acuteST-elevation myocardial infarction: an individual patient-data pooled analysis of 11 trials. Eur Heart J 2009;30(18):2193203.

[25] Stone GW, Witzenbichler B, Guagliumi G, Peruga JZ, BrodieBR, Dudek D, et al. Bivalirudin during primary PCI in acutemyocardial infarction. N Engl J Med 2008;358(21):221830.

[26] ten Berg J, vant Hof A, Dill T, Heestermans T, van WerkumJW, Mosterd A, et al. Effect of early, pre-hospital initiation ofhigh bolus dose tirofiban in patients with ST-segment eleva-tion myocardial infarction on short- and long-term clinical

outcome. J Am Coll Cardiol 2010;55(22):244655.[27] Tousek P, Rokyta R, Tesarova J, Pudil R, Belohlavek J,

Stasek J, et al. Routine upfront abciximab versus standardperi-procedural therapy in patients undergoing primaryper-cutaneous coronary intervention for cardiogenic shock. In:The PRAGUE-7 study, in ESC congress 2009. European Soci-ety of Cardiology; 2009.

[28] Hosmane VR,Mustafa NG, ReddyVK, Reese CL,DiSabatinoA, Kolm P, et al. Survival and neurologic recovery in patientswith ST-segment elevation myocardial infarction resusci-tatedfrom cardiac arrest.J Am CollCardiol 2009;53(5):40915.

[29] Mehta SR, Tanguay JF, Eikelboom JW, Jolly SS, Joyner CD,Granger CB, et al. Double-dose versus standard-dose clopi-dogrel and high-dose versus low-dose aspirin in individualsundergoing percutaneous coronary intervention for acutecoronary syndromes (CURRENT-OASIS 7): a randomisedfactorial trial. Lancet 2010. Sept 1 [Epub ahead of print].

[30] Dangas G, Mehran R, Guagliumi G, Caixeta A, WitzenbichlerB, Aoki J, et al. Role of clopidogrel loading dose in patientswith ST-segment elevation myocardial infarction undergo-ing primary angioplasty: results from the HORIZONS-AMI(harmonizing outcomes with revascularization and stentsin acute myocardial infarction) trial. J Am Coll Cardiol2009;54(15):1348436.

[31] Montalescot G, Wiviott SD, Braunwald E, Murphy SA,Gibson CM, McCabe CH, et al. Prasugrel compared withclopidogrel in patients undergoing percutaneous coro-nary intervention for ST-elevation myocardial infarction(TRITON-TIMI 38): double-blind, randomised controlledtrial. Lancet 2009;373(9665):72331.

[32] Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuels-

son H, Held C, et al. Ticagrelor versus clopidogrel inpatients with acute coronary syndromes. N Engl J Med2009;361(11):104557.

[33] Wiviott SD, Braunwald E, McCabe CH, Montalescot G,Ruzyllo W, Gottlieb S, et al. Prasugrel versus clopidogrelin patients with acute coronary syndromes. N Engl J Med2007;357(20):200115.

[34] MehtaSR, Granger CB, Eikelboom JW,Bassand JP, WallentinL, Faxon DP, et al. Efficacy and safety of fondaparinux versusenoxaparin in patients with acute coronary syndromesundergoing percutaneous coronary intervention: resultsfromthe OASIS-5 trial.J Am CollCardiol2007;50(18):174251.

[35] Fox KAA, Bassand JP, Mehta SR, Wallentin L, Theroux P,Piegas LS, et al. Influence of renal function on the efficacyand safety of fondaparinux relative to enoxaparin in non ST-segment elevation acute coronary syndromes. Ann Intern

Med 2007;147(5):30410.[36] Giugliano RP, White JA, Bode C, Armstrong PW, Montale-

scot G, Lewis BS, et al. Early versus delayed, provisionaleptifibatide in acute coronary syndromes. N Engl J Med2009;360(21):217690.

[37] Stone GW, McLaurin BT, CoxDA, Bertrand ME, Lincoff AM,Moses JW, et al. Bivalirudin for patients with acute coronarysyndromes. N Engl J Med 2006;355(21):220316.

[38] Kastrati A, Neumann FJ, Mehilli J, Byrne RA, Iijima R, Bt-tner HJ, et al. Bivalirudin versus unfractionated heparinduring percutaneous coronary intervention. N Engl J Med2008;359(7):68896.


16/16

ARTICLE IN PRESS

GUIDELINE

ADDENDUM



[39] Rao S, OGrady K, Pieper K, Granger C, Newby L, Mahaf-fey K, et al. A comparison of the clinical impact ofbleeding measured by two different classifications amongpatients with acute coronary syndromes. J Am Coll Cardiol2006;47(4):80916.

[40] White HD, Ohman EM, Lincoff AM, Bertrand ME, ColomboA, McLaurin BT, et al. Safety and efficacy of bivalirudin with

and without glycoprotein IIb/IIIa inhibitors in patients withacute coronary syndromes undergoing percutaneous coro-nary intervention: 1-year results from the ACUITY (AcuteCatheterization and Urgent Intervention Triage strategY)trial. J Am Coll Cardiol 2008;52(10):80714.

[41] Alexander KP, Chen AY, Roe MT, Newby LK, Gibson CM,Allen-LaPointe NM, et al. Excess dosing of antiplatelet andantithrombinagents in the treatment of non-ST-segment ele-vation acute coronary syndromes. JAMA 2005;294(24):3108.

[42] Moscucci M, Fox KAA, Cannon CP, Klein W, Lopez-SendonJ, Montalescot G, et al. Predictors of major bleeding in acutecoronary syndromes: the Global Registry of Acute CoronaryEvents (GRACE). Eur Heart J 2003;24(20):1815.

[43] Rao S, OGrady K, Pieper KS, Granger CB, Newby LK, Vande Werf F, et al. Impact of bleeding severity on clinical out-comes among patients with acute coronary syndromes. Am

J Cardiol 2005;96(9):12006.[44] Manoukian SV, Feit F, Mehran R, Voeltz MD, Ebrahimi R,

Hamon M, et al. Impact of major bleeding on 30-day mor-tality and clinical outcomes in patients with acute coronarysyndromes: an analysis from the ACUITY trial. J Am CollCardiol 2007;49(12):13628.

[45] Rao SV, Jollis JG, Harrington RA, Granger CB, Newby LK,Armstrong PW, et al. Relationship of blood transfusion andclinical outcomes in patients withacute coronary syndromes.

JAMA 2004;292(13):155562.[46] Santopinto JJ, Fox KAA, Goldberg RJ, Budaj A, Pi nero G,

Avezum A, et al. Creatinine clearance and adverse hospi-tal outcomes in patients with acute coronary syndromes:findings from the global registry of acute coronary events(GRACE). Heart 2003;89(9):10038.

[47] Brasselet C, Tassan S, Nazeyrollas P, Hamon M, Metz D.Randomised comparison of femoral versus radial approachfor percutaneous coronary intervention using abciximab inacute myocardial infarction: results of theFARMItrial.Heart2007;93(12):155661.

[48] Jolly SS, Amlani S, Hamon M, Yusuf S, Mehta SR. Radialversus femoral access for coronary angiography or interven-tion and the impact on major bleeding and ischemic events:a systematic review and meta-analysis of randomized trials.Am Heart J 2009;157(1):13240.

[49] Nikolsky E, Mehran R, Dangas G, Fahy M, Na Y, PocockSJ, et al. Development and validation of a prognostic risk

score for major bleeding in patients undergoing percuta-neous coronary intervention via the femoral approach. EurHeart J 2007;28(16):193645.

[50] Subherwal S, Bach RG, Chen AY, Gage BF, Rao SV, NewbyLK, et al. Baseline risk of major bleeding in non-ST-segment-elevation myocardial infarction: the CRUSADE(Can Rapid risk stratification of Unstable angina patients

Suppress ADverse outcomes with Early implementationof the ACC/AHA Guidelines) Bleeding Score. Circulation2009;119(14):187382.

[51] Mehran R, Pocock S, Nikolsky E, Clayton T, Dangas G,Kirtane A, et al. A risk score to predict bleeding inpatients with acute coronary syndromes. J Am Coll Cardiol2010;55(23):255666.

[52] Cabello JB,BurlsA, EmparanzaJI, BaylissS, Quinn T. Oxygentherapy for acute myocardial infarction. Cochrane DatabaseSyst Rev 2010;(6), doi:10.1002/14651858.CD007160.pub2 [Art.

No. CD007160].[53] HutchisonAW, MalaiapanY, JarvieI, BargerB, WatkinsEGB,

Braitberg G, et al. Prehospital 12-lead ECG to triage ST-elevation myocardial infarction and emergency departmentactivation of the infarct team significantly improves door-to-balloon times: ambulance Victoria and MonashHEARTAcuteMyocardial Infarction (MonAMI) 12-lead ECG project.Circ Cardiovasc Interv 2009;2(6):52834.

[54] Carstensen S, Nelson GC, Hansen PS, Macken L, Irons S,Flynn M, et al. Field triage to primary angioplasty com-binedwith emergencydepartmentbypassreduces treatmentdelays and is associated with improved outcome. Eur Heart

J 2007;28(19):23139.[55] Bonnefoy E, Steg PG, Boutitie F, Dubien P, Lapostolle F,

Roncalli J, et al. Comparison of primary angioplasty andpre-hospitalfibrinolysis in acutemyocardialinfarction(CAP-TIM) trial: a 5-year follow-up. Eur Heart J 2009;30(13):1598606.

[56] Brieger D, Kelly AM, Aroney C, Tideman P, Freedman SB,Chew D, et al. Acute coronary syndromes: consensus rec-ommendations for translating knowledge into action. Med J

Aust 2009;191(6):3348.[57] Bradley EH, Nallamothu BK, Curtis JP, Webster TR, Magid

DJ, Granger CB, et al. Summary of evidence regarding hos-pital strategies to reduce door-to-balloon times for patientswith ST-segment elevation myocardial infarction undergo-ing primary percutaneous coronary intervention. Crit PathwCardiol 2007;6(3):917.

[58] Bradley EH, Herrin J, Wang Y, Barton BA, Webster TR,Mattera J, et al. Strategies for reducing the door-to-balloon time in acute myocardial infarction. N Engl J Med2006;22(355):230820.

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