1. Dallas 2015 TFQO: Darren Walters EVREVs: EVREV 1: Darren Walters COI #422 EVREV 2: Chris Ghaemmaghami COI #89 Taskforce: Acute Coronary Syndrome Fibrinolytic therapy prior to hospital vs fibrinolytic after hospital arrival

2. Dallas 2015 COI Disclosure (specific to this systematic review) Commercial/industry nil Potential intellectual conflicts nil

3. Dallas 2015 2010 CoSTR 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.

4. Dallas 2015 C2015 PICO Population:Among adults who are suspected of having ST-elevation myocardial infarction outside of a hospital Intervention:does fibrinolytic therapy prior to hospital arrival Comparison:compared with fibrinolytic therapy after hospital arrival Outcomes:change death 9-Critical ICH 8- Critical revascularization 7-Critical major bleeding 6-Important stroke 6-Important reinfarction 5-Important

5. Dallas 2015 Inclusion/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 papers Metanalysis 2 RCTs, 3 non-RCTs 60 Excluded 273 papers

6. Dallas 2015 Inclusion/Exclusion & Articles Found Previous metanalysis by Morrison JAMA 2000 (6 RCTs) EMIP 1993 included NSTEMI unable to sub stratify data GREAT 1992 no ST elevation –suspicion of STEMI Roth 1990 used alternate monthly rotational allocations Cochrane review includes 3 studies Reviewed the worksheet ACS-018B 2010 COSTAR 32 studies.

7. Dallas 2015 2015 Proposed Treatment Recommendations We recommend using pre-hospital fibrinolysis in comparison to in hospital fibrinolysis for STEMI to reduce the risk (Strong recommendation, low level of evidence). Values and preferences statement: In making this recommendation we place a higher value on early reperfusion when fibrinolysis is the planned treatment strategy. In the prehospital setting, and should be administered by health care professionals using well-established protocols, competency training programs, and quality assurance programs, under medical oversight

8. Dallas 2015 Risk of Bias in studies RCT bias assessment StudyYearDesign Total Patien ts Populati on Industry Funding Allocation: Generation Allocation: Concealment Blinding: Participants Blinding: Assessors Outcome: Complete Outcome: Selective Other Bias Castaigne 1989RCT100OHCA NoUnclearHigh highHighLowUnclear Schofer 1990RCT78OHCA NolowLow UnclearHighLow Weaver 1993RCT360OHCA nolowLowHighLowUnclearHighLow

9. Dallas 2015 Key data from key studies Weaver 1993 1211 P:Among adults who are suspected of having ST-elevation myocardial infarction outside of a hospital I:does fibrinolytic therapy prior to hospital arrival C:compared with fibrinolytic therapy after hospital arrival O:change death 9-Critical ICH 8-Critical revascularization 7-Critical major bleeding 6-Important stroke 6-Important reinfarction 5- Important Mean difference in time to treatment 33 minutes±18 minutes.

10. Dallas 2015 Evidence profile table(s)

11. Dallas 2015 Evidence profile table(s)

12. Dallas 2015 Forest plot and risk of bias

13. Dallas 2015 Forest Plot bleeding

14. Dallas 2015 Forrest plot ICH

15. Dallas 2015 Forrest plot CVA

16. Dallas 2015 Proposed Consensus on Science statements For the critical outcome of “survival to hospital discharge” we have identified low quality evidence (downgraded for imprecision) from three RCTs (Castiagne 1989 30A, Schofer 1990 1429,Weaver 1993 1211) enrolling 531 patients showing benefit (OR 0.46 95% CI 0.23 – 0.93). For the critical outcome of “bleeding” we have identified low quality evidence (downgraded for imprecision) from two RCTs (Schofer 1990 1429,Weaver 1993 1211) enrolling 223 patients showing adverse outcome (OR 0.96 95% CI 0.40 – 2.42) For the important outcome of “ICH” we have identified low quality evidence (downgraded for imprecision) from one RCTs (Weaver 1993 1211) enrolling 223 patients showing adverse outcome (OR 2.14 95% CI 0.39 – 11.84) For the important outcome of “ICH” we have identified moderate quality evidence (downgraded for imprecision) from one RCTs (Weaver 1993 1211) enrolling 223 patients showing adverse outcome (OR 2.14 95% CI 0.39 – 11.84)

17. Dallas 2015 Draft Treatment Recommendations We recommend using pre-hospital fibrinolysis in comparison to in hospital fibrinolysis for STEMI to reduce the risk (Strong recommendation, low level of evidence). Values and preferences statement: In making this recommendation we place a higher value on early reperfusion when fibrinolysis is the planned treatment strategy. In the prehospital setting, and should be administered by health care professionals using well-established protocols, competency training programs, and quality assurance programs, under medical oversight

18. Dallas 2015 Knowledge Gaps (eg. ETT vs BVM) Other specific worksheets that would be helpful Specific research required Time delay at which the benefit of prehospital fibrinolysis equals the benefit of in hospital fibrinolysis. RCT conducted in the ‘modern’ era of reperfusion.

19. Dallas 2015 Next Steps This slide will be completed during Task Force Discussion (not EvRev) and should include: Consideration of interim statement Person responsible Due date Essential slide (one slide only). Estimated time <30 sec