Effectiveness and Safety of P2Y12 Inhibitor Pretreatment for Primary PCI in STEMI: Systematic Review and Meta-analysis

Supplemental Digital Content is Available in the Text. Abstract: Dual antiplatelet therapy with aspirin and P2Y12 inhibitors in patients with ST-segment elevation myocardial infarction (STEMI) has been shown to be associated with better outcomes. Yet, there is uncertainty regarding the optimal timing for its initiation. We performed a systematic review and meta-analysis of evidence on pretreatment with P2Y12 inhibitors in combination with aspirin in patients with STEMI undergoing primary percutaneous coronary intervention (PCI). We performed a systematic search of electronic databases PubMed, CENTRAL, and Scopus until April 2022. Studies were eligible if they compared P2Y12 inhibitor upstream administration with downstream use in patients with STEMI submitted to PCI. Studies with patients receiving fibrinolysis or medical therapy only were excluded. Outcomes were assessed at the shortest follow-up available. Of 2491 articles, 3 RCT and 16 non-RCT studies were included, with a total of 79,300 patients (66.1% pretreated, 66.0% treated with clopidogrel). Pretreatment was associated with reduction in definite stent thrombosis (odds ratio [OR] 0.61 [0.38–0.98]), all-cause death (OR 0.77 [0.60–0.97]), and cardiogenic shock (OR 0.60 [0.48–0.75]). It was also associated with a lower incidence of thrombolysis in myocardial infarction flow <3 pre-PCI (OR 0.78 [0.67–0.92]). However, incidence of recurrent MI was not significantly reduced (OR 0.93 [0.57–1.52]). Regarding safety, pretreatment was not associated with a higher risk of major bleeding events (OR 0.83 [0.75–0.92]). Pretreatment with dual antiplatelet therapy, including a P2Y12 inhibitor, was associated with better pre-PCI coronary perfusion, lower incidence of definite stent thrombosis, cardiogenic shock, and, possibly, all-cause mortality with no sign of potential harm encountered.

[1]  A. V. Van't Hof,et al.  Effect of prehospital treatment in STEMI patients undergoing primary PCI , 2022, Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions.

[2]  C. Granger,et al.  Pre-Hospital Antiplatelet Therapy for STEMI Patients Undergoing Primary Percutaneous Coronary Intervention: What We Know and What Lies Ahead , 2021, Thrombosis and Haemostasis.

[3]  J. Mimoso,et al.  P2Y12 inhibitor loading dose before catheterization in ST-segment elevation myocardial infarction: Is this the best strategy? , 2020, Revista portuguesa de cardiologia : orgao oficial da Sociedade Portuguesa de Cardiologia = Portuguese journal of cardiology : an official journal of the Portuguese Society of Cardiology.

[4]  T. Huynh,et al.  The effect of ASA, ticagrelor, and heparin in ST‐segment myocardial infarction patients with prolonged transport times to primary percutaneous intervention , 2020, Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions.

[5]  E. Omerovic,et al.  Pretreatment with P2Y12 receptor antagonists in ST-elevation myocardial infarction: a report from the Swedish Coronary Angiography and Angioplasty Registry , 2019, European heart journal.

[6]  P. Steg,et al.  Pre-treatment with a P2Y12 antagonist before PCI in STEMI: why should we wait? , 2019, European heart journal.

[7]  F. Bartolomucci,et al.  Time‐dependent benefits of pre‐treatment with new oral P2Y12‐inhibitors in patients addressed to primary PCI for acute ST‐elevation myocardial infarction , 2018, Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions.

[8]  J. Ferrières,et al.  One-Year Survival After ST-Segment–Elevation Myocardial Infarction in Relation With Prehospital Administration of Dual Antiplatelet Therapy: The FAST-MI Program , 2018, Circulation. Cardiovascular interventions.

[9]  C. Reid,et al.  Pretreatment with dual antiplatelet therapy in patients with ST‐elevation myocardial infarction , 2018, Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions.

[10]  Deepak L. Bhatt,et al.  The efficacy of early versus delayed P2Y12 inhibition in percutaneous coronary intervention for ST-elevation myocardial infarction: a systematic review and meta-analysis. , 2018, EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology.

[11]  G. Hindricks,et al.  2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. , 2017, Revista espanola de cardiologia.

[12]  T. Henry,et al.  The safety and effectiveness of adenosine diphosphate receptor inhibitor pretreatment among acute myocardial infarction patients treated with percutaneous coronary intervention in community practice: Insights from the TRANSLATE‐ACS study , 2017, Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions.

[13]  I. Porto,et al.  Pre-hospital ticagrelor in patients with ST-segment elevation myocardial infarction with long transport time to primary PCI facility. , 2016, Cardiovascular revascularization medicine : including molecular interventions.

[14]  A. Kastrati,et al.  Pre-treatment with P2Y12 inhibitors in ACS patients: who, when, why, and which agent? , 2016, European heart journal.

[15]  D. Angiolillo,et al.  Reviewing the controversy surrounding pre-treatment with P2Y12 inhibitors in acute coronary syndrome patients , 2016, Expert review of cardiovascular therapy.

[16]  E. Vicaut,et al.  Effect of Pre-Hospital Ticagrelor During the First 24 h After Primary Percutaneous Coronary Intervention in Patients With ST-Segment Elevation Myocardial Infarction: The ATLANTIC-H²⁴ Analysis. , 2015, JACC. Cardiovascular interventions.

[17]  G. Schuler,et al.  Association of upstream clopidogrel administration and myocardial reperfusion assessed by cardiac magnetic resonance imaging in patients with ST-elevation myocardial infarction , 2014, European heart journal. Acute cardiovascular care.

[18]  I. Porto,et al.  Comparison of pre-hospital 600 mg or 900 mg vs. peri-interventional 300 mg clopidogrel in patients with ST-elevation myocardial infarction undergoing primary coronary angioplasty. The Load&Go randomized trial. , 2013, International journal of cardiology.

[19]  K. Huber,et al.  Efficacy and safety of a high loading dose of clopidogrel administered prehospitally to improve primary percutaneous coronary intervention in acute myocardial infarction: the randomized CIPAMI trial , 2012, Clinical Research in Cardiology.

[20]  H. Schuchlenz,et al.  Clopidogrel pre-treatment is associated with reduced in-hospital mortality in primary percutaneous coronary intervention for acute ST-elevation myocardial infarction. , 2011, European heart journal.

[21]  S. Steinhubl,et al.  Clopidogrel pretreatment in ST-elevation myocardial infarction patients transferred for percutaneous coronary intervention. , 2010, American heart journal.

[22]  Claes Held,et al.  Ticagrelor versus clopidogrel in patients with acute coronary syndromes. , 2009, The New England journal of medicine.

[23]  V. Boyko,et al.  Usefulness of pretreatment with high-dose clopidogrel in patients undergoing primary angioplasty for ST-elevation myocardial infarction. , 2009, The American journal of cardiology.

[24]  D. Moher,et al.  Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement , 2009, BMJ : British Medical Journal.

[25]  W. Gibler,et al.  Patterns of upstream antiplatelet therapy use before primary percutaneous coronary intervention for acute ST-elevation myocardial infarction (from the CRUSADE National Quality Improvement Initiative). , 2008, The American journal of cardiology.

[26]  R. Kornowski,et al.  Effect of clopidogrel pretreatment on angiographic and clinical outcomes in patients undergoing primary percutaneous coronary intervention for ST-elevation acute myocardial infarction. , 2008, The American journal of cardiology.

[27]  E. Antman,et al.  Prasugrel versus clopidogrel in patients with acute coronary syndromes. , 2007, The New England journal of medicine.

[28]  F. Neumann,et al.  Time Dependence of Platelet Inhibition After a 600-mg Loading Dose of Clopidogrel in a Large, Unselected Cohort of Candidates for Percutaneous Coronary Intervention , 2005, Circulation.

[29]  Suong V. Hoa,et al.  Conception And Design , 2002 .

[30]  R. Babu The article , 2020, International Journal of Computing Algorithm.

[31]  G. Montalescot,et al.  Prehospital ticagrelor in ST-segment elevation myocardial infarction. , 2014, The New England journal of medicine.

[32]  M. T. Ryan,et al.  Supplemental Digital Content , 2013 .

[33]  Deepak L. Bhatt,et al.  2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. , 2013, Circulation.

[34]  K. Mahaffey,et al.  ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation , 2012 .

[35]  D. Moher,et al.  Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. , 2010, International journal of surgery.