学术急诊医学档案

卷 14 编号 1 (2026)

Early Oral P2Y12 Inhibitor Loading in Patients with ST-segment Eleva-tion Myocardial Infarction Undergoing Primary PCI: A Systematic Re-view and Meta-analysis

学术急诊医学档案, 卷 14 编号 1 (2026), 1 七月 2025 , 第 e58 页
https://doi.org/10.22037/aaem.v14i1.3137

摘要

Introduction: Whether oral P2Y12 inhibitor loading should be given before hospital arrival or deferred until angiography remains uncertain in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). We compared the efficacy and safety of early loading with later in-hospital, catheterization-laboratory, downstream, or no pretreatment. Methods: PubMed/MEDLINE, Embase, Scopus, and Web of Science were searched from inception through July 2026 without a language restriction. Randomized and nonrandomized comparative studies of adults with STEMI undergoing primary PCI were eligible. Primary random-effects meta-analyses used restricted maximum likelihood (REML) when at least three independent studies were available. A direct prehospital analysis was defined in the working analysis plan before final pooling. Because the review was not prospectively registered, these analytical decisions are described as predefined rather than as claims of prospective protocol registration. Results: Twenty-six studies were included, comprising three randomized trials and 23 nonrandomized studies. In the primary REML analysis, early P2Y12 loading was associated with higher pre-PCI thrombolysis in myocardial infarction (TIMI) 2/3 flow (8 studies; odds ratio (OR): 1.37, 95% confidence interval (CI): 1.03 to 1.83; p=0.032; I²=87.5%) and pre-PCI TIMI 3 flow (9 studies; OR: 1.39, 95% CI: 1.03 to 1.88; p=0.029; I²=83.5%), but neither association retained nominal significance after Knapp–Hartung adjustment. Thirty-day recurrent myocardial infarction/re-infarction was lower in the primary model (10 studies; OR: 0.70, 95% CI: 0.50 to 0.96; p=0.029), although Egger testing suggested possible small-study effects (p=0.079) and leave-one-out analyses were not uniformly stable. Thirty-day stroke was also lower (6 studies; OR: 0.69, 95% CI: 0.56 to 0.85; p<0.001), but this estimate lost significance in sensitivity analysis. Six-month mortality was higher in a three-study primary analysis (OR: 1.18, 95% CI: 1.09 to 1.29; p<0.001), but the Knapp–Hartung CI included the null (0.99 to 1.41) and one registry contributed 99.6% of the random-effects weight. Major bleeding was not increased (14 studies; OR: 1.05, 95% CI: 0.86 to 1.28; p=0.655). Conclusions: The certainty of evidence was very low for every pooled outcome-time stratum. Primary analyses suggested possible improvements in pre-PCI patency and selected ischemic outcomes without a detectable increase in major bleeding, but several positive estimates were not robust to Knapp–Hartung or influence analyses. The isolated six-month mortality signal was likewise statistically fragile. Further studies are needed, yet current evidence does not establish a routine pretreatment benefit for oral P2Y12 inhibitor use in all patients with STEMI undergoing primary PCI.

关键词:
  • ST-Segment Elevation Myocardial Infarction
  • Percutaneous Coronary Intervention
  • Ticagrelor
  • Clopidogrel

参考

1. Rao SV, O’Donoghue ML, Ruel M, Rab T, Tamis-Holland JE, Alexander JH, et al. 2025 ACC/AHA/ACEP/NAEMSP/SCAI guideline for the management of patients with acute coro-nary syndromes: a report of the American College of Cardiol-ogy/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2025;151(13):e771-e862.

2. Byrne RA, Rossello X, Coughlan JJ, Barbato E, Berry C, Chieffo A, et al. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J. 2023;44(38):3720-3826.

3. De Luca G, Suryapranata H, Ottervanger JP, Antman EM. Time delay to treatment and mortality in primary angioplasty for acute myocardial infarction: every minute of delay counts. Circulation. 2004;109(10):1223-1225.

4. Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361(11):1045-1057.

5. Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357(20):2001-2015.

6. Montalescot G, Bolognese L, Dudek D, Goldstein P, Hamm C, Tanguay JF, et al. Pretreatment with prasugrel in non-ST-segment elevation acute coronary syndromes. N Engl J Med. 2013;369(11):999-1010.

7. Zeymer U, Arntz HR, Mark B, Fichtlscherer S, Werner G, Schöller R, et al. Efficacy and safety of a high loading dose of clopidogrel administered prehospitally to improve primary percutaneous coronary intervention in acute myocardial in-farction: the randomized CIPAMI trial. Clin Res Cardiol. 2012;101(4):305-312.

8. Ducci K, Grotti S, Falsini G, Angioli P, Liistro F, Mandò M, 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. Int J Cardiol. 2013;168(5):4814-4816.

9. Montalescot G, van ’t Hof AW, Lapostolle F, Silvain J, Lassen JF, Bolognese L, et al. Prehospital ticagrelor in ST-segment el-evation myocardial infarction. N Engl J Med. 2014;371(11):1016-1027.

10. Dörler J, Edlinger M, Alber HF, Altenberger J, Benzer W, Grimm G, et al. Clopidogrel pre-treatment is associated with reduced in-hospital mortality in primary percutaneous coro-nary intervention for acute ST-elevation myocardial infarc-tion. Eur Heart J. 2011;32(23):2954-2961.

11. Redfors B, Dworeck C, Haraldsson I, Angerås O, Oden-stedt J, Ioanes D, et al. Pretreatment with P2Y12 receptor antagonists in ST-elevation myocardial infarction: a report from the Swedish Coronary Angiography and Angioplasty Registry. Eur Heart J. 2019;40(15):1202-1210.

12. Koul S, Smith JG, Götberg M, Omerovic E, Alfredsson J, Venetsanos D, et al. No benefit of ticagrelor pretreatment compared with treatment during percutaneous coronary in-tervention in patients with ST-segment-elevation myocardial infarction undergoing primary PCI. Circ Cardiovasc Interv. 2018;11(3):e005528.

13. Rohla M, Ye SX, Shibutani H, Bruno J, Otsuka T, Häner JD, et al. Pretreatment with P2Y12 inhibitors in ST-segment ele-vation myocardial infarction: insights from the Bern-PCI Reg-istry. JACC Cardiovasc Interv. 2024;17(1):17-28.

14. Gewehr DM, Carvalho PEP, Dagostin CS, Cardoso R, Kubrusly TBL, Kubrusly FB, et al. Pretreatment with P2Y12 inhibitors in ST-elevation myocardial infarction: a systematic review and meta-analysis. Catheter Cardiovasc Interv. 2023;102(2):200-211.

15. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an up-dated guideline for reporting systematic reviews. BMJ. 2021;372: n71.

16. Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editors. Cochrane Handbook for System-atic Reviews of Interventions. 2nd ed. Chichester (UK): John Wiley & Sons;2019.

17. Sterne JAC, Hernán MA, Reeves BC, Savović J, Berkman ND, Viswanathan M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355: i4919.

18. Veroniki AA, Jackson D, Viechtbauer W, Bender R, Bowd-en J, Knapp G, et al. Methods to estimate the between-study variance and its uncertainty in meta-analysis. Res Synth Methods. 2016;7(1):55-79.

19. Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measur-ing inconsistency in meta-analyses. BMJ. 2003;327(7414):557-560.

20. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50(4):1088-1101.

21. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629-634.

22. Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, et al. GRADE: an emerging consensus on rat-ing quality of evidence and strength of recommendations. BMJ. 2008;336(7650):924-926.

23. StataCorp. Stata Statistical Software: Release 18. College Station (TX): StataCorp LLC;2023.

24. Alexander D, Mann N, Ou FS, Peterson ED, Ohman EM, Gibler WB, 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. Am J Cardiol. 2008;102(10):1335-1340.

25. Almendro-Delia M, Hernández-Meneses B, Padilla-Rodríguez G, Blanco-Ponce E, Arboleda-Sánchez JA, Rodríguez-Yáñez JC, et al. Timing of P2Y12 inhibitor admin-istration in patients with STEMI undergoing primary PCI. J Am Coll Cardiol. 2024;83(25):2629-2639.

26. Danchin N, Puymirat E, Cayla G, Cottin Y, Coste P, Gilard M, et al. One-year survival after ST-segment-elevation myo-cardial infarction in relation with prehospital administration of dual antiplatelet therapy: the FAST-MI program. Circ Car-diovasc Interv. 2018;11(9):e007241.

27. de Waha S, Eitel I, Desch S, Fuernau G, Lurz P, Schuler G, et al. Association of upstream clopidogrel administration and myocardial reperfusion assessed by cardiac magnetic reso-nance imaging in patients with ST-elevation myocardial in-farction. Eur Heart J Acute Cardiovasc Care. 2014;3(2):110-117.

28. Fefer P, Hod H, Hammerman H, Segev A, Beinart R, Boyko V, et al. Usefulness of pretreatment with high-dose clopidogrel in patients undergoing primary angioplasty for ST-elevation myocardial infarction. Am J Cardiol. 2009;104(4):514-518.

29. Gallo F, Cutolo A, Antonucci A, Cordoni G, Demurtas E, Panza A, et al. Clinical impact of P2Y12 pretreatment in ST-segment elevation myocardial infarction: insights from the SEMPRE study. Am J Cardiol. 2025;243:1-7.

30. Koul S, Smith JG, Scherstén F, James S, Lagerqvist B, Er-linge D. Effect of upstream clopidogrel treatment in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. Eur Heart J. 2011;32(23):2989-2997.

31. Larson DM, Duval S, Sharkey SS, Solie C, Tschautscher C, Lips DL, et al. Clopidogrel pretreatment in ST-elevation myo-cardial infarction patients transferred for percutaneous cor-onary intervention. Am Heart J. 2010;160(1):202-207.

32. Lev EI, Kornowski R, Vaknin-Assa H, Brosh D, Fuchs S, Battler A, et al. Effect of clopidogrel pretreatment on angio-graphic and clinical outcomes in patients undergoing primary PCI for ST-elevation acute myocardial infarction. Am J Cardi-ol. 2008;101(4):435-439.

33. Lupi A, Schaffer A, Lazzero M, Tessitori M, De Martino L, Rognoni A, et al. Pre-hospital ticagrelor in patients with ST-segment elevation myocardial infarction with long transport time to primary PCI facility. Cardiovasc Revasc Med. 2016;17(8):528-534.

34. Guedes JPM, Marques N, Azevedo P, Mota T, Bispo J, Fer-nandes R, et al. P2Y12 inhibitor loading dose before cathe-terization in ST-segment elevation myocardial infarction: is this the best strategy? Rev Port Cardiol. 2020;39(10):553-561.

35. Pepe M, Cafaro A, Paradies V, Signore N, Addabbo F, Bortone AS, et al. Time-dependent benefits of pre-treatment with new oral P2Y12 inhibitors in patients addressed to pri-mary PCI for acute ST-elevation myocardial infarction. Cathe-ter Cardiovasc Interv. 2019;93(4):592-601.

36. Postma S, Dambrink JHE, Ottervanger JP, Gosselink ATM, Koopmans PC, ten Berg JM, et al. Early ambulance initiation versus in-hospital initiation of high-dose clopidogrel in ST-segment elevation myocardial infarction. Thromb Haemost. 2014;112(3):606-613.

37. Qadeer A, Khawar M, Abdul Ghaffar QB, Jain S, Fouad M, Kanwal K, et al. Impact of P2Y12 inhibitor pretreatment on clinical outcomes in ST-segment elevation myocardial infarc-tion undergoing percutaneous coronary intervention: a ret-rospective cohort study. Catheter Cardiovasc Interv. 2026;107(4):1100-1111.

38. Tohamy AR, Maher HR, Hasan-Ali HR. Effect of ticagrelor loading time on the outcomes of primary percutaneous coro-nary intervention. Iran Heart J. 2026;27(2):17-26.

39. Yudi MB, Farouque O, Andrianopoulos N, Ajani AE, Brennan A, Lefkovits J, et al. Pretreatment with dual an-tiplatelet therapy in patients with ST-elevation myocardial in-farction. Catheter Cardiovasc Interv. 2018;92(2):E98-E105.

40. Fabris E, Menzio S, Gregorio C, Pezzato A, Stolfo D, Ale-ksova A, et al. Effect of prehospital treatment in STEMI pa-tients undergoing primary PCI. Catheter Cardiovasc Interv. 2022;99(5):1500-1508.

41. Mateus PS, Moreira I, Bernardo M, Azevedo LS, Gavina C, Moreira JI, et al. Pretreatment with P2Y12 inhibitors in STEMI patients referred to primary PCI: insights from a na-tional registry. Thromb Haemost. 2025;125(Suppl 1): A1-A43.

42. Elhadad A, Sulman D, Procopi N, Devos P, Beaupré F, Braik N, et al. Pre-treatment with P2Y12 inhibitors in acute myocardial infarction with cardiogenic shock. Eur Heart J Cardiovasc Pharmacother. 2025;11(6):489-499.

43. Greco A, Scalia L, Laudani C, Spagnolo M, Mauro MS, Sammartino S, et al. Downstream cangrelor versus upstream ticagrelor in patients with ST-segment elevation myocardial infarction: a propensity score-matched analysis. Int J Cardiol. 2025;418:132660.

44. Cayla G, Lapostolle F, Ecollan P, Stibbe O, Benezet JF, Henry P, et al. Pre-hospital ticagrelor in ST-segment elevation myocardial infarction in the French ATLANTIC population. Int J Cardiol. 2017;244:49-53.

45. Montalescot G, van ’t Hof AW, Bolognese L, Cantor WJ, Cequier A, Chettibi M, et al. Effect of pre-hospital ticagrelor during the first 24 h after primary percutaneous coronary intervention in patients with ST-segment elevation myocar-dial infarction: the ATLANTIC-H24 analysis. JACC Cardiovasc Interv. 2016;9(7):646-656.

46. Bellemain-Appaix A, Bégué C, Bhatt DL, Ducci K, Harring-ton RA, Roe MT, et al. The efficacy of early versus delayed P2Y12 inhibition in PCI for ST-elevation myocardial infarc-tion: a systematic review and meta-analysis. EuroInterven-tion. 2018;14(1):78-85.

47. Chou YH, Huang CC, Chang CK, Huang JL, Jang BH, Lee TH, et al. The coronary reperfusion effect and safety of pre-hospital P2Y12 inhibitor in primary-PCI STEMI patients: a systematic review and meta-analysis. Prehosp Emerg Care. 2024;28(7):937-946.

48. Parodi G, Bellandi B, Xanthopoulou I, Capranzano P, Capodanno D, Valenti R, et al. Morphine is associated with delayed activity of oral antiplatelet agents in patients with ST-elevation acute myocardial infarction undergoing primary PCI. Circ Cardiovasc Interv. 2015;8(1):e001593.

49. Kubica J, Adamski P, Ostrowska M, Sikora J, Kubica JM, Sroka WD, et al. Morphine delays and attenuates ticagrelor exposure and action in patients with myocardial infarction: the IMPRESSION trial. Eur Heart J. 2016;37(3):245-252.

50. Dawson LP, Chen D, Dagan M, Bloom JE, Taylor AJ, Duffy SJ, et al. Assessment of pretreatment with oral P2Y12 inhibi-tors and cardiovascular and bleeding outcomes in patients with non-ST elevation acute coronary syndromes: a systemat-ic review and meta-analysis. JAMA Netw Open. 2021;4(11):e2134322.

51. Kovacevic MK, Bjelobrk MB, Srdanovic IS, Tadic ST, Ilic AI, Petrovic MP, et al. Impact of P2Y12 inhibitor pretreat-ment on baseline TIMI flow and short-term outcomes in STEMI patients undergoing primary PCI: a 10-year single-center study. Eur Heart J. 2025;46(Suppl 1): ehaf784. 1793.

  • 摘要 ##plugins.themes.ojsPlusA.frontend.article.viewed##: 31 ##plugins.themes.ojsPlusA.frontend.article.times##
  • pdf (English) ##plugins.themes.ojsPlusA.frontend.article.downloaded##: 28 ##plugins.themes.ojsPlusA.frontend.article.times##

##plugins.themes.ojsPlusA.frontend.article.downloadstatastics##

##plugins.block.makeSubmission.linkLabel##

##plugins.block.makeSubmission.linkLabel##

SJR

SCImago Journal & Country Rank

COPE

最新一期

消息