Dallas 2015

TFQO: Karen Woolfrey COI #261EVREV 1: Karen Woolfrey COI 261EVREV 2: Daniel Pichel COI # 513

Taskforce: ACS

ACS 335: Pre-hospital ADP-Receptor Antagonist in

STEMI

Dallas 2015COI Disclosure

EVREV 1 COI# 261Commercial/industry• No conflicts of Interest

Potential intellectual conflicts• No conflicts of Interest

EVREV 2 COI# 513Commercial/industry• No conflicts of Interest

Potential intellectual conflicts• No conflicts of Interest

Dallas 2015

2010 Treatment Recommendation

Clopidogrel: “ Administration of clopidogrel in addition to standard care (aspirin, anticoagulants, and/or reperfusion) for patients determined to have moderate to high-risk non-ST elevation ACS and STEMI is recommended. The ideal oral loading dose of clopidogrel in patients </-75 years of age is dependent on the planned approach: 600 mg in a planned invasive strategy; or 300 mg in a planned noninvasive strategy or together with fibrinolysis. The ideal dose in patients >/-75 years of age has not yet been delineated, but may range from 75 to 600 mg”.

Dallas 2015

2010 Treatment RecommendationPrasugrel: “May be administered after angiography

to patients with NSTEMI presenting with stenoses amenableto PCI. ED or prehospital administration of clopidogrelshould be withheld even in patients who are not at high riskfor bleeding (age <75 years, no history of previous stroke orTIA, and body weight >60 kg), pending consideration ofprasugrel administration following angiography. In patientswho are not at high risk for bleeding with planned PCI,prasugrel (60 mg oral loading dose) may be substituted forclopidogrel for patients determined to have STEMI less than12 hours after the initial symptoms. Prasugrel is not

recommended in STEMI patients receiving fibrinolysis”.

Dallas 2015

2010 Treatment Recommendation

Ticagrelor: “Administration of ticagrelor (180-mg oral loading dose) in addition to standard care (aspirin, anticoagulants, and/or reperfusion) determined to have non-ST elevation ACS or STEMI managed with early invasive strategy by hospital personnel may be an option instead of clopidogrel. The risks and/or benefits of ticagrelor in STEMI patients managed with fibrinolysis is unknown”.

Dallas 2015C2015 PICO

Population: Patients with suspected ST-Elevation Myocardial Infarction (STEMI) identified outside the hospital (pre-hospital)Intervention: Pre-hospital administration of an ADP-receptor antagonist (Clopidogrel, Prasugrel, or Ticagrelor)Comparison: Upstream administration in the hospitalOutcomes: 30-day mortality (9); major bleeding(6)

Dallas 2015

Inclusion/Exclusion& Articles Found

Only randomized control trials (RCT) were includedExclusions

No in-hospital comparator groupStudies that did not randomize patients in the pre-hospital setting

The search yielded a total of 159 RCT15 articles reviewed (11 full text articles; 4 conference abstracts)12 excluded (5-no comparator; 1-no clinical outcome; 5- not relevant; 1-no pre-hospital group)3 RCT were included for bias assessment

Dallas 2015Draft Treatment Recommendations

We have insufficient confidence in the treatment effect to recommend a change in practice (weak recommendation, very low quality of evidence)

In making this recommendation we place a higher value on not recommending new resource allocation to an unproven intervention over uncertain benefits of mortality

Dallas 2015 Risk of Bias in studies

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30-day Mortality (9)

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Major Bleeding (6)

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30-day Mortality (9)

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Major Bleeding (6)

Dallas 2015Proposed Consensus on Science statements

For the critical outcome of 30-day mortality, we have identified very low quality of evidence (downgraded for imprecision and reporting bias) from three RCTs (Zeymer 2012, 305; Ducci 2013, 4814; Montalescot 2014; 1) enrolling 2365 patients showing no differential benefit to pre-hospital administration of an ADP-receptor antagonist compared to in hospital administration (OR 1.58 95% CI 0.90-2.78)

Dallas 2015Proposed Consensus on Science statements

For the important outcome of major bleeding, we have identified very low quality of evidence (downgraded for imprecision and reporting bias) from three RCTs (Zeymer 2012, 305; Ducci 2013, 4814; Montalescot 2014, 1) enrolling 2365 patients showing no differential benefit to pre-hospital administration of an ADP-receptor antagonist compared to in hospital administration (OR 1.12 95% CI 0.72-1.74)

Dallas 2015Draft Treatment Recommendations

In pre-hospital identified STEMI patients with a planned primary PCI approach, we have insufficient confidence in the treatment effect for pre-hospital administration of an ADP-receptor antagonist compared to in-hospital administration to recommend a change in existing practice (very low quality of evidence, weak recommendation)

In making this recommendation we place a higher value on not recommending new resource allocation to an unproven intervention over uncertain benefits of mortality

Dallas 2015

Knowledge Gaps

Specific research requiredRCT comparing the ADP-receptor antagonists use in pre-hospital setting in STEMIAre these agents recommended in STEMI managed by fibrinolysis?