Dallas 2015 TFQO: Hiroshi Nonogi #254 EVREVs: Hiroshi Nonogi #254 Tony Scott #138 Taskforce: ACS Fibrinolytic and immediate PCI for STEMI 882

Dallas 2015 COI Disclosure (SPECIFIC to this systematic review) EVREV 1 Hiroshi Nonogi #254 Commercial/industry : None Potential intellectual conflicts: None EVREV 2 Tony Scott #138 Commercial/industry: None Potential intellectual conflicts: None

Dallas Treatment Recommendation The routine use of fibrinolysis-facilitated PPCI, compared with PPCI, is not recommended in patients with suspected STEMI.

Dallas 2015 C2015 PICO Population: patients who are having ST- elevation myocardial infarction in the emergency department Intervention: fibrinolytic administration combined with immediate PCI Comparison: immediate PCI alone Outcomes: death, reinfarction, urgent target vessel revascularization, major bleeding, intracranial hemorrhage

Dallas 2015 Inclusion/Exclusion/Articles Found List Inclusions/Exclusions Inclusion criteria: study comparing primary (immediate) PCI with thrombolysis-based facilitated PCI, and RCT Exclusion criteria: Rescue PCI only for failed thrombolysis, primary PCI with antithrombotic regimen including IIb/IIIa inhibitors or antithrombin drugs for facilitated PCI, and half dose lytic

Dallas 2015 After Banff, re-review using ILCOR librarian search strategy

Dallas 2015 RCT 5 articles 2726

Dallas 2015 Risk of Bias in studies table

Dallas 2015 Outcome: Death Outcome: Nonfatal MI ROB: serious due to unclear for selection bias 、 Inconsistency::serious due to high i2 Imprecision: serious due to no significant difference→ Very low quality of evidence Imprecision: serious due to no significant difference →Moderate quality of evidence

Dallas 2015 Outcome: Major Bleeding Outcome: Intracranial hemorrhage High quality of evidence Imprecision : serious due to few events (n=14) →Moderate quality of evidence

Dallas 2015 Outcome: Revascularization ROB: serious due to unclear for selection bias, Inconsistency : serious due to heterogeniety p=0.01, i2=71% and Imprecision: serious due to no significant difference → very low quality of evidence

Dallas 2015 NS harm

Dallas 2015

1.Unclear for selection bias 2.Performance bias is high in 3 studies, however for death, riskof bias is not serious. 3.Heterogeneity; P=0.85, i2=0%<40% 4.All 5 studies used tPA. 5.More than 2000 cases (3533) with 189 events, OR: NS 6.no high risk in 2 studies 7.heterogeneity: P=0.49, i2=0% 8.more than 2000 case with few events (14 cases) 9.concealment unclear 10.heterogeneity; P=0.01, i2=71% 11.OR heterogeneity; P=0.18, i2=36% 13.OR: , NS

Dallas 2015 Proposed Consensus on Science statements For the critical outcome of mortality, we have identified moderate quality of evidence (downgraded for imprecision) from 5 RCTs (Van de Werf, F., 2006, 569; Ellis, S. G,2008,2205; Itoh, T., 2010, 1625; Kurihara, H., 2004,e14; Thiele, H.,2006,1132) enrolling 3533 patients showing no benefit (OR % CI 0.96 to 1.74) when fibrinolytic administration is combined with immediate PCI vs immediate PCI alone. For the critical outcome of nonfatal MI, we have identified very low quality of evidence (downgraded for bias, inconsistency, and imprecision) from 5 RCTs (Van de Werf, F., 2006, 569; Ellis, S. G,2008,2205; Itoh, T., 2010, 1625; Kurihara, H., 2004,e14; Thiele, H.,2006,1132) enrolling 3498 patients showing no benefit (OR % CI 0.73 to 1.81). For the critical outcome of target vessel revascularization, we have identified very low quality of evidence (downgraded for bias, inconsistency and imprecision) from 4 RCTs (Van de Werf, F., 2006, 569; Ellis, S. G,2008,2205; Itoh, T., 2010, 1625; Kurihara, H., 2004, e14) enrolling 3360 patients showing no benefit (OR % CI 0.91 to 1.47).

Dallas 2015 Proposed Consensus on Science statements For the critical outcome of intracranial hemorrhage, we have identified moderate quality evidence (downgraded for imprecision) from 3 RCTs (Van de Werf, F., 2006, 569; Ellis, S. G,2008,2205; Itoh, T., 2010, 1625) enrolling 3342 patients showing harm (OR % CI 1.39 to 43.15) when fibrinolytic administration is combined with immediate PCI vs immediate PCI alone. For the important outcome of major bleeding, we have identified high quality of evidence from 5 RCTs (Van de Werf, F., 2006, 569; Ellis, S. G,2008,2205; Itoh, T., 2010, 1625; Kurihara, H., 2004,e14; Thiele, H.,2006,1132) enrolling 3543 patients showing harm (OR % CI 1.05 to 2.20).

Dallas 2015 Draft Treatment Recommendations We recommend against the routine use of fibrinolytic administration combined with immediate PCI, compared with immediate PCI alone in patients with ST elevation myocardial infarction. (strong recommendation, low quality of evidence). In making this recommendation, we place a higher value on avoiding harm when the evidence available suggests no benefit and potential harm in fibrinolytic administration combined with immediate PCI.

Dallas 2015 Knowledge Gaps *DO NOT USE FOR PLENARY* - BREAKOUT ONLY Other specific systematic review that would be helpful Relationship with delayed PCI after fibrinolysis Specific research required Facilitated and delayed PCI with new anti- coagulants