Chicago 2014

TFQO: Darren Walters COI #317 EVREV 1: Darren Walters COI #317EVREV 2: Chris Ghaemmaghami COI #60 Taskforce: Acute Coronary Syndrome

In STEMI (P), does fibrinolytic therapy prior to hospital arrival

(I), compared with fibrinolytic therapy after hospital arrival

(C), change outcomes(O)?ACS 338

Chicago 2014COI Disclosure

Chris Ghaemmaghami COI #60Commercial/industryPotential intellectual conflicts

Darren Walters COI #317Commercial/industry• Nil

Potential intellectual conflicts• Editor IJC, HLC

Chicago 20142010 Treatment Recommendation

In patients with STEMI diagnosed in the prehospital setting,reperfusion may be achieved by administration of fibrinolytics by healthcare providers in the field. Alternately, fibrinolytic therapy may be administered on arrival at hospital. If fibrinolysis is chosen as the reperfusion strategy, it should be started as soon as possible,ideally in the prehospital setting,and should be administered by paramedics, nurses, or doctors using well-established protocols, competency training programs, and quality assurance programs, under medical oversight.

Chicago 2014C2015 PICO

Population:Among adults who are suspected of having ST-elevation myocardial infarction outside of a hospitalIntervention:does fibrinolytic therapy prior to hospital arrivalComparison:compared with fibrinolytic therapy after hospital arrivalOutcomes:change death 9-Critical ICH 8-Critical revascularization 7-Critical major bleeding 6-Important stroke 6-Important reinfarction 5-Important

Chicago 2014Inclusion/Exclusion& Articles Found

(“myocardial infarction”[MH] OR AMI[ti] OR “STEMI”[TI] OR “st-elevation”[ti] OR “st elevation”[ti] OR “ST-segment”[TI] OR “ST segment”[TI] OR “infarct*”[ti] OR “myocardial ischemia”[MH] OR “coronary thrombosis”[MH]) AND (“myocardial reperfusion”[MH] OR fibrinoly*[tiab] OR fibrinolytic agents[MH] OR thrombolytic therapy[MH] OR thromboly*[tiab] OR reteplase[TI] OR anistreplase[TI] OR ER-TIMI[TI] OR “tissue plasminogen activator”[TI] OR “tissue plasminogen activator”[MH] OR alteplase[TI] OR rt-PA[TI] OR TPA[TI] OR tenecteplase[TI] OR streptokinase[TI] OR APSAC[TI]) AND (""Emergency medical technicians""[MH] OR ""pre-hospital""[TI] OR ""prehospital""[TI] OR ""ambulance""[TI] OR “ambulances”[MH] OR ""paramedic*""[TI] OR “Emergency medical services”[MH] OR “EMS”[TI] OR “EMT”[TI] OR “out-of-hospital”[TI] OR “out of hospital”[TI] OR “emergency physician*”[TI] OR mobile[TI] OR “before hospital”[TI]) NOT (“animals”[MH] NOT “humans”[MH]) NOT (“editorial”[PT] OR “letter”[PT] OR “comment”[PT] OR “review”[PT] OR “practice guideline”[PT]) NOT ""score""[TI] AND ((("randomized controlled trial"[PT] OR “controlled clinical trial”[PT] OR “clinical trial”[PT] OR “comparative study”[PT] OR random*[TIAB] OR controll*[TIAB] OR “intervention study”[TIAB] OR “experimental study”[TIAB] OR “comparative study”[TIAB] OR trial[TIAB] OR evaluat*[TIAB] OR “Before and after”[TIAB] OR “interrupted time series”[TIAB]) NOT ("animals"[MH] NOT (animals[MH] AND "humans"[MH]))) OR ("Epidemiologic Studies"[Mesh] OR “case control”[TIAB] OR “case-control”[TIAB] OR ((case[TIAB] OR cases[TIAB]) AND (control[TIAB] OR controls[TIAB)) OR “cohort study”[TIAB] OR “cohort analysis”[TIAB] OR “follow up study”[TIAB] OR “follow-up study”[TIAB] OR “observational study”[TIAB] OR “longitudinal”[TIAB] OR “retrospective”[TIAB] OR “cross sectional”[TIAB] OR “cross-sectional”[TIAB] OR questionnaire[TIAB] OR questionnaires[TIAB] OR questionnaires[TIAB] OR survey[TIAB]))) NOT ("letter"[pt] OR "comment"[pt] OR "editorial"[pt])

279 papersMetanalysis 2RCTs, 3non-RCTs 60excluded

Chicago 2014

Previousmet analysis by Morrison JAMA 2000 (6 RCTs)EMIP 1993 included NSTEMI unable to sub stratify dataGREAT 1992 no ST elevation –suspicion of STEMIRoth 1990 used alternate monthly rotational allocations

Cochrane review includes 3 studiesReviewed the worksheet ACS-018B 2010 COSTAR

32 studies.

Inclusion/Exclusion& Articles Found

Chicago 20142015 Proposed Treatment Recommendations

We suggest using pre-hospital fibrinolysis in comparison to in-hospital fibrinolysis for STEMIto reduce the risk of all cause in-hospital mortality based on a low level of evidence.

Chicago 2014 Risk of Bias in studies

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Forest plot and risk of bias

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Forest Plot bleeding

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Forrest plot ICH

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Forrest plot CVA

Chicago 2014Evidence profile table(s)

Chicago 2014Evidence profile table(s)

Chicago 2014Evidence profile table(s)

Chicago 2014

Reviewed non randomised studies 2009-201485 studies First pass 7 studies in detail

Armstrong 2010 STREAM vs PCIBata 2009 WEST vs PCICastle 2007 retrospective decision analsyisKhan 2009 actuarial survival onlyKoeth 2009 eligible for rct vs ineligible Smith 2011 no outcomes paramedic decisionsZeymer 2009 non RCT cohort comparison

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Forrest plot incl non RCTMortality

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Forrest plot incl non RCTBleeding

CVA

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Re infarction

Forrest plot incl non RCT

Chicago 2014Proposed Consensus on Science statements

Insert Summary statement(s) from SEERs* For the important outcome of “all cause hospital mortality” we have identified low quality evidence (downgraded for bias allocation and concealment) from three RCTs enrolling 538 patients showing benefit (OR 0.46 95% CI 0.23 – 0.93).

For the outcome of Bleeding complications a moderate level of evidence from 2 RCTS enrolling 438 patients showed no benefit (OR 0.96 95% CI 0.40-2.32)

For the outcome of stroke a low level of evidence from one study enrolling 360 patients showed no benefit (OR 2.14 95% CI 0.39-11.84)

For the outcome of intracranial haemorhage a moderate level of evidence was found from 2 studies enrolling 438 patients showed no benefit (OR 2.14 95% CI 0.39-11.84)

For other outcomes no evidence from RCTs was found.

For reinfarction a low level of evidence from one non RCT showed enrolling 778 patients showed no benefit (OR 1.09 95% CI 0.55- 2.15)

Chicago 2014Draft Treatment Recommendations

We suggest using pre-hospital fibrinolysis in comparison to in hospital fibrinolysis for STEMIto reduce the risk of all cause in hospital mortality based on a low level of evidence.