Association of Pretreatment With P2Y12 Receptor Antagonists Preceding Percutaneous Coronary Intervention in Non–ST-Segment Elevation Acute Coronary Syndromes With Outcomes | Acute Coronary Syndromes | JAMA Network Open | JAMA Network
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1.
Hamm  CW, Bassand  JP, Agewall  S,  et al; ESC Committee for Practice Guidelines.  ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: the task force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC).   Eur Heart J. 2011;32(23):2999-3054. doi:10.1093/eurheartj/ehr236PubMedGoogle ScholarCrossref
2.
Amsterdam  EA, Wenger  NK, Brindis  RG,  et al.  2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.   J Am Coll Cardiol. 2014;64(24):e139-e228. doi:10.1016/j.jacc.2014.09.017PubMedGoogle ScholarCrossref
3.
Steinhubl  SR, Berger  PB, Brennan  DM, Topol  EJ; CREDO Investigators.  Optimal timing for the initiation of pre-treatment with 300 mg clopidogrel before percutaneous coronary intervention.   J Am Coll Cardiol. 2006;47(5):939-943. doi:10.1016/j.jacc.2005.10.047PubMedGoogle ScholarCrossref
4.
Steinhubl  SR, Berger  PB, Mann  JT  III,  et al; CREDO Investigators; Clopidogrel for the Reduction of Events During Observation.  Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial.   JAMA. 2002;288(19):2411-2420. doi:10.1001/jama.288.19.2411PubMedGoogle ScholarCrossref
5.
Mehta  SR, Yusuf  S, Peters  RJ,  et al; Clopidogrel in Unstable angina to prevent Recurrent Events trial (CURE) Investigators.  Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study.   Lancet. 2001;358(9281):527-533. doi:10.1016/S0140-6736(01)05701-4PubMedGoogle ScholarCrossref
6.
Zeymer  U, Arntz  HR, Mark  B,  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.   Clin Res Cardiol. 2012;101(4):305-312. doi:10.1007/s00392-011-0393-1PubMedGoogle ScholarCrossref
7.
Bellemain-Appaix  A, Kerneis  M, O’Connor  SA,  et al; ACTION Study Group.  Reappraisal of thienopyridine pretreatment in patients with non-ST elevation acute coronary syndrome: a systematic review and meta-analysis.   BMJ. 2014;349:g6269. doi:10.1136/bmj.g6269PubMedGoogle ScholarCrossref
8.
Sabatine  MS, Cannon  CP, Gibson  CM,  et al; Clopidogrel as Adjunctive Reperfusion Therapy (CLARITY)-Thrombolysis in Myocardial Infarction (TIMI) 28 Investigators.  Effect of clopidogrel pretreatment before percutaneous coronary intervention in patients with ST-elevation myocardial infarction treated with fibrinolytics: the PCI-CLARITY study.   JAMA. 2005;294(10):1224-1232. doi:10.1001/jama.294.10.1224PubMedGoogle ScholarCrossref
9.
Bellemain-Appaix  A, Bégué  C, Bhatt  DL,  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.   EuroIntervention. 2018;14(1):78-85. doi:10.4244/EIJ-D-17-00852PubMedGoogle ScholarCrossref
10.
Montalescot  G, Bolognese  L, Dudek  D,  et al; ACCOAST Investigators.  Pretreatment with prasugrel in non-ST-segment elevation acute coronary syndromes.   N Engl J Med. 2013;369(11):999-1010. doi:10.1056/NEJMoa1308075 PubMedGoogle ScholarCrossref
11.
Roffi  M, Patrono  C, Collet  JP,  et al; ESC Scientific Document Group.  2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC).   Eur Heart J. 2016;37(3):267-315. doi:10.1093/eurheartj/ehv320PubMedGoogle ScholarCrossref
12.
Råmunddal  T, Hoebers  LP, Henriques  JP,  et al.  Prognostic impact of chronic total occlusions: a report from SCAAR (Swedish Coronary Angiography and Angioplasty Registry).   JACC Cardiovasc Interv. 2016;9(15):1535-1544.PubMedGoogle ScholarCrossref
13.
Fröbert  O, Lagerqvist  B, Olivecrona  GK,  et al; TASTE Trial.  Thrombus aspiration during ST-segment elevation myocardial infarction.   N Engl J Med. 2013;369(17):1587-1597. doi:10.1056/NEJMoa1308789PubMedGoogle ScholarCrossref
14.
World Health Organization.  International Statistical Classification of Diseases, Tenth Revision (ICD-10). World Health Organization; 1992.
15.
Sahlén  A, Varenhorst  C, Lagerqvist  B,  et al.  Outcomes in patients treated with ticagrelor or clopidogrel after acute myocardial infarction: experiences from SWEDEHEART registry.   Eur Heart J. 2016;37(44):3335-3342. doi:10.1093/eurheartj/ehw284PubMedGoogle ScholarCrossref
16.
Harris  KM, Remler  DK.  Who is the marginal patient: understanding instrumental variables estimates of treatment effects.   Health Serv Res. 1998;33(5 Pt 1):1337-1360.PubMedGoogle Scholar
17.
McClellan  M, McNeil  BJ, Newhouse  JP.  Does more intensive treatment of acute myocardial infarction in the elderly reduce mortality: analysis using instrumental variables.   JAMA. 1994;272(11):859-866. doi:10.1001/jama.1994.03520110039026PubMedGoogle ScholarCrossref
18.
Rassen  JA, Schneeweiss  S, Glynn  RJ, Mittleman  MA, Brookhart  MA.  Instrumental variable analysis for estimation of treatment effects with dichotomous outcomes.   Am J Epidemiol. 2009;169(3):273-284. doi:10.1093/aje/kwn299PubMedGoogle ScholarCrossref
19.
Stukel  TA, Fisher  ES, Wennberg  DE, Alter  DA, Gottlieb  DJ, Vermeulen  MJ.  Analysis of observational studies in the presence of treatment selection bias: effects of invasive cardiac management on AMI survival using propensity score and instrumental variable methods.   JAMA. 2007;297(3):278-285. doi:10.1001/jama.297.3.278PubMedGoogle ScholarCrossref
20.
Brookhart  MA, Rassen  JA, Schneeweiss  S.  Instrumental variable methods in comparative safety and effectiveness research.   Pharmacoepidemiol Drug Saf. 2010;19(6):537-554. doi:10.1002/pds.1908PubMedGoogle ScholarCrossref
21.
Schüpke  S, Neumann  F-J, Menichelli  M,  et al; ISAR-REACT 5 Trial Investigators.  Ticagrelor or prasugrel in patients with acute coronary syndromes.   N Engl J Med. 2019;381(16):1524-1534. doi:10.1056/NEJMoa1908973PubMedGoogle ScholarCrossref
22.
Stone  GW, McLaurin  BT, Cox  DA,  et al; ACUITY Investigators.  Bivalirudin for patients with acute coronary syndromes.   N Engl J Med. 2006;355(21):2203-2216. doi:10.1056/NEJMoa062437 PubMedGoogle ScholarCrossref
23.
Hansson  EC, Dellborg  M, Lepore  V, Jeppsson  A.  Prevalence, indications and appropriateness of antiplatelet therapy in patients operated for acute aortic dissection: associations with bleeding complications and mortality.   Heart. 2013;99(2):116-121. doi:10.1136/heartjnl-2012-302717PubMedGoogle ScholarCrossref
24.
Hofmann  R, James  SK, Jernberg  T,  et al; DETO2X–SWEDEHEART Investigators.  Oxygen therapy in suspected acute myocardial infarction.   N Engl J Med. 2017;377(13):1240-1249. doi:10.1056/NEJMoa1706222PubMedGoogle ScholarCrossref
25.
Götberg  M, Christiansen  EH, Gudmundsdottir  IJ,  et al; iFR-SWEDEHEART Investigators.  Instantaneous wave-free ratio versus fractional flow reserve to guide PCI.   N Engl J Med. 2017;376(19):1813-1823. doi:10.1056/NEJMoa1616540PubMedGoogle ScholarCrossref
26.
Erlinge  D, Koul  S, Eriksson  P,  et al.  Bivalirudin versus heparin in non-ST and ST-segment elevation myocardial infarction: a registry-based randomized clinical trial in the SWEDEHEART registry (the VALIDATE-SWEDEHEART trial).   Am Heart J. 2016;175:36-46. doi:10.1016/j.ahj.2016.02.007PubMedGoogle ScholarCrossref
27.
De Luca  L, D’Ascenzo  F, Musumeci  G,  et al.  Incidence and outcome of switching of oral platelet P2Y12 receptor inhibitors in patients with acute coronary syndromes undergoing percutaneous coronary intervention: the SCOPE registry.   EuroIntervention. 2017;13(4):459-466. doi:10.4244/EIJ-D-17-00092PubMedGoogle ScholarCrossref
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    Original Investigation
    Cardiology
    October 1, 2020

    Association of Pretreatment With P2Y12 Receptor Antagonists Preceding Percutaneous Coronary Intervention in Non–ST-Segment Elevation Acute Coronary Syndromes With Outcomes

    Author Affiliations
    • 1Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden
    • 2Department of Cardiology, Danderyd University Hospital, Stockholm, Sweden
    • 3Department of Cardiology, Skåne University Hospital, Lund, Sweden
    • 4Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden
    • 5Department of Cardiology, Östersund Hospital, Östersund, Sweden
    • 6Division of Cardiology, Department of Clinical Science and Education, Karolinska Institutet, Södersjukhuset, Stockholm, Sweden
    • 7Department of Clinical Science and Education, Karolinska Institutet, Cardiology Capio Sankt Goran Hospital, Stockholm, Sweden
    • 8Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
    JAMA Netw Open. 2020;3(10):e2018735. doi:10.1001/jamanetworkopen.2020.18735
    Key Points

    Question  Is a pretreatment strategy with P2Y12 receptor antagonists associated with better outcomes vs no pretreatment in patients with non–ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention?

    Findings  This cohort study including 64 857 patients from the Swedish Coronary Angiography and Angioplasty Registry found that pretreatment with P2Y12 receptor antagonists was not associated with improved survival nor a lower risk of stent thrombosis but was associated with increased risk of bleeding.

    Meaning  These findings suggest that pretreatment with P2Y12 receptor antagonists should not be routinely used in non–ST-segment elevation acute coronary syndrome.

    Abstract

    Importance  Pretreatment of patients with non–ST-segment elevation acute coronary syndrome (NSTE-ACS) with P2Y12 receptor antagonists is a common practice despite the lack of definite evidence for its benefit.

    Objective  To investigate the association of P2Y12 receptor antagonist pretreatment vs no pretreatment with mortality, stent thrombosis, and in-hospital bleeding in patients with NSTE-ACS undergoing percutaneous coronary intervention (PCI).

    Design, Setting, and Participants  This cohort study used prospective data from the Swedish Coronary Angiography and Angioplasty Registry of 64 857 patients who underwent procedures between 2010 and 2018. All patients who underwent PCI owing to NSTE-ACS in Sweden were stratified by whether they were pretreated with P2Y12 receptor antagonists. Associations of pretreatment with P2Y12 receptor antagonists with the risks of adverse outcomes were investigated using instrumental variable analysis and propensity score matching. Data were analyzed from March to June 2019.

    Exposures  Pretreatment with P2Y12 receptor antagonists.

    Main Outcomes and Measures  The primary end point was all-cause mortality within 30 days. Secondary end points were 1-year mortality, stent thrombosis within 30 days, and in-hospital bleeding.

    Results  In total, 64 857 patients (mean [SD] age, 64.7 [10.9] years; 46 809 [72.2%] men) were included. A total of 59 894 patients (92.4%) were pretreated with a P2Y12 receptor antagonist, including 27 867 (43.7%) pretreated with clopidogrel, 34 785 (54.5%) pretreated with ticagrelor, and 1148 (1.8%) pretreated with prasugrel. At 30 days, there were 971 deaths (1.5%) and 101 definite stent thromboses (0.2%) in the full cohort. Pretreatment was not associated with better survival at 30 days (odds ratio [OR], 1.17; 95% CI, 0.66-2.11; P = .58), survival at 1 year (OR, 1.34; 95% CI, 0.77-2.34; P = .30), or decreased stent thrombosis (OR, 0.81; 95% CI, 0.42-1.55; P = .52). However, pretreatment was associated with increased risk of in-hospital bleeding (OR, 1.49; 95% CI, 1.06-2.12; P = .02).

    Conclusions and Relevance  This cohort study found that pretreatment of patients with NSTE-ACS with P2Y12 receptor antagonists was not associated with improved clinical outcomes but was associated with increased risk of bleeding. These findings support the argument that pretreatment with P2Y12 receptor antagonists should not be routinely used in patients with NSTE-ACS.

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