Download PDF
Thromb Haemost 2018; 118(05): 852-863
DOI: 10.1055/s-0038-1635578
Cellular Haemostasis and Platelets
Schattauer GmbH Stuttgart

Early P2Y12 Inhibitors Escalation in Primary PCI Patients: Insights from the RENOVAMI Registry

Alessandro Lupi
1   Division of Cardiology, ASL VCO, Verbania, Italy
,
Roberta Della Bona
2   Department of Cardiology, Policlinico Casilino, Rome, Italy
,
Emanuele Meliga
3   Interventional Cardiology Unit, Mauriziano Hospital, Turin, Italy
,
Davide Capodanno
4   Department of Cardio-Thoracic-Vascular, Ferrarotto Hospital, University of Catania, Catania, Italy
,
Alon Schaffer
1   Division of Cardiology, ASL VCO, Verbania, Italy
,
Angelo S. Bongo
5   2nd Division of Cardiology, “Maggiore della Carità” University Hospital, Novara, Italy
,
Giovanni Gaudio
6   Medicina Interna, Presidio Ospedaliero Somma Lombardo, Lombardo, Italy
,
Luigina Guasti
7   Research Center on Dyslipidemia, University of Insubria, Varese, Italy
,
Dimitrios Alexopoulos
8   Attikon University Hospital, National and Capodistrian University of Athens, Athens, Greece
,
Marco Valgimigli
9   Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland
,
Italo Porto
10   Interventional Cardiology Unit, Department of Cardiovascular Sciences, UCSC, Rome, Italy
› Author Affiliations Funding None.
Further Information

Publication History

26 September 2017

26 February 2018

Publication Date:
04 April 2018 (online)

Also available at
    Permissions and Reprints

Abstract

Background Early escalation from clopidogrel to new generation P2Y12 inhibitors is common practice in patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). Real-world data about this strategy, however, are limited.

Methods From 2012 to 2015, 1,057 consecutive STEMI patients treated with pPCI in an Italian hub-and-spoke network were prospectively included in an observational registry (RENOVAMI, ClinicalTrials.gov Identifier: NCT01760382). We compared the prevalence, predictive factors and in-hospital outcomes of patients escalated to a new generation P2Y12 inhibitor within the first 24 hours from pPCI with those continuing on admission antiplatelet therapy.

Results In the first 24 hours after pPCI, 165 patients (15.6%) were escalated from clopidogrel to a new generation P2Y12 inhibitor, while de-escalation to clopidogrel was occasional (19 patients, 1.8%) and switch between new generation P2Y12 inhibitors was rare (8 patients, 0.8%, all from ticagrelor to prasugrel). Drug eluting stent use (adjusted odds ratio [OR], 2.19, 95% confidence interval [CI], 1.55–3.08, p = 0.0002) and impaired renal function (adjusted OR, 0.19, 95% CI, 0.05–0.77, p = 0.02) were the only independent predictive factors for the decision to escalate. After adjustment for potential confounders, escalation did not predict in-hospital outcomes, whereas the overall use of new generation P2Y12 inhibitors was correlated with a better in-hospital survival (adjusted hazard ratio, 0.47, 95% CI, 0.25–0.91, p = 0.03). Moreover, escalation did not influence bleeding rates.

Conclusions In this prospective registry of STEMI patients treated with pPCI and contemporary antiplatelet therapy, early escalation to a new generation P2Y12 inhibitor appeared safe and did not significantly affect in-hospital bleeding rates.

Keywords

antiplatelet therapy - clopidogrel - ticagrelor - prasugrel - STEMI - primary PCI - antiplatelet therapy escalation
 

  • References

  • 1 Wiviott SD, Braunwald E, McCabe CH. , et al; TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007; 357 (20) 2001-2015
    CrossrefPubMedGoogle Scholar
  • 2 Wallentin L, Becker RC, Budaj A. , et al; PLATO Investigators. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361 (11) 1045-1057
    CrossrefPubMedGoogle Scholar
  • 3 O'Gara PT, Kushner FG, Ascheim DD. , et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 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. Circulation 2013; 127 (04) e362-e425
    CrossrefPubMedGoogle Scholar
  • 4 Steg PG, James SK, Atar D. , et al; Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC). ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2012; 33 (20) 2569-2619
    CrossrefPubMedGoogle Scholar
  • 5 De Luca L, Leonardi S, Cavallini C. , et al; EYESHOT Investigators. Contemporary antithrombotic strategies in patients with acute coronary syndrome admitted to cardiac care units in Italy: the EYESHOT Study. Eur Heart J Acute Cardiovasc Care 2015; 4 (05) 441-452
    CrossrefPubMedGoogle Scholar
  • 6 Windecker S, Kolh P, Alfonso F. , et al; Authors/Task Force members. 2014 ESC/EACTS Guidelines on myocardial revascularization: the Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J 2014; 35 (37) 2541-2619
    CrossrefPubMedGoogle Scholar
  • 7 Rollini F, Franchi F, Angiolillo DJ. Switching P2Y12-receptor inhibitors in patients with coronary artery disease. Nat Rev Cardiol 2016; 13 (01) 11-27
    CrossrefPubMedGoogle Scholar
  • 8 Montalescot G, Wiviott SD, Braunwald E. , et al; TRITON-TIMI 38 investigators. Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): double-blind, randomised controlled trial. Lancet 2009; 373 (9665): 723-731
    CrossrefPubMedGoogle Scholar
  • 9 Koul S, Andell P, Martinsson A. , et al. A pharmacodynamic comparison of 5 anti-platelet protocols in patients with ST-elevation myocardial infarction undergoing primary PCI. BMC Cardiovasc Disord 2014; 14: 189
    CrossrefPubMedGoogle Scholar
  • 10 Alexopoulos D, Xanthopoulou I, Deftereos S. , et al. In-hospital switching of oral P2Y12 inhibitor treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention: prevalence, predictors and short-term outcome. Am Heart J 2014; 167 (01) 68-76.e2
    CrossrefPubMedGoogle Scholar
  • 11 Bagai A, Wang Y, Wang TY. , et al. In-hospital switching between clopidogrel and prasugrel among patients with acute myocardial infarction treated with percutaneous coronary intervention: insights into contemporary practice from the national cardiovascular data registry. Circ Cardiovasc Interv 2014; 7 (04) 585-593
    CrossrefPubMedGoogle Scholar
  • 12 Clemmensen P, Grieco N, Ince H. , et al; MULTIPRAC study investigators. MULTInational non-interventional study of patients with ST-segment elevation myocardial infarction treated with PRimary Angioplasty and Concomitant use of upstream antiplatelet therapy with prasugrel or clopidogrel--the European MULTIPRAC Registry. Eur Heart J Acute Cardiovasc Care 2015; 4 (03) 220-229
    CrossrefPubMedGoogle Scholar
  • 13 De Luca G, Verdoia M, Schaffer A. , et al. Switching from high-dose clopidogrel to prasugrel in ACS patients undergoing PCI: a single-center experience. J Thromb Thrombolysis 2014; 38 (03) 388-394
    CrossrefPubMedGoogle Scholar
  • 14 Lerman TT, Zahger D, Arad J, Gilutz H, Reitblat O, Shimony A. In-hospital switching from clopidogrel to prasugrel following thrombolysis for ST-elevation myocardial infarction: a 3-year single center experience. Eur Heart J Acute Cardiovasc Care 2016; 5 (03) 271-276
    CrossrefPubMedGoogle Scholar
  • 15 Parodi G, De Luca G, Bellandi B. , et al. Switching from clopidogrel to prasugrel in patients having coronary stent implantation. J Thromb Thrombolysis 2014; 38 (03) 395-401
    PubMedGoogle Scholar
  • 16 Loh JP, Pendyala LK, Kitabata H. , et al. Safety of reloading prasugrel in addition to clopidogrel loading in patients with acute coronary syndrome undergoing percutaneous coronary intervention. Am J Cardiol 2013; 111 (06) 841-845
    CrossrefPubMedGoogle Scholar
  • 17 Sherwood MW, Wiviott SD, Peng SA. , et al. Early clopidogrel versus prasugrel use among contemporary STEMI and NSTEMI patients in the US: insights from the National Cardiovascular Data Registry. J Am Heart Assoc 2014; 3 (02) e000849
    CrossrefPubMedGoogle Scholar
  • 18 Almendro-Delia M, Blanco Ponce E, Gomez-Domínguez R. , et al. Safety and efficacy of in-hospital clopidogrel-to-prasugrel switching in patients with acute coronary syndrome. An analysis from the ‘real world’. J Thromb Thrombolysis 2015; 39 (04) 499-507
    CrossrefPubMedGoogle Scholar
  • 19 Schiele F, Puymirat E, Lorgis L. , et al. Switch and non switch in P2Y12 inhibition: the real life use of clopidogrel and prasugrel in patients with acute myocardial infarction. Insights from the FAST MI 2010 registry. Eur Heart J 2012; 33 (01) 204
    PubMedGoogle Scholar
  • 20 Chandrasekhar J, Hibbert B, Froeschl M, So D, Mehran R, May ML. ; CAPITAL investigators. The impact of switching P2Y12 receptor inhibitor therapy during index hospitalization: a systematic review. Eur J Clin Pharmacol 2016; 72 (01) 83-91
    CrossrefPubMedGoogle Scholar
  • 21 Mehran R, Rao SV, Bhatt DL. , et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation 2011; 123 (23) 2736-2747
    CrossrefPubMedGoogle Scholar
  • 22 Steg PG, James S, Harrington RA. , et al; PLATO Study Group. Ticagrelor versus clopidogrel in patients with ST-elevation acute coronary syndromes intended for reperfusion with primary percutaneous coronary intervention: a Platelet Inhibition and Patient Outcomes (PLATO) trial subgroup analysis. Circulation 2010; 122 (21) 2131-2141
    CrossrefPubMedGoogle Scholar
  • 23 Biasucci LM, Porto I, Di Vito L. , et al. Differences in microparticle release in patients with acute coronary syndrome and stable angina. Circ J 2012; 76 (09) 2174-2182
    CrossrefPubMedGoogle Scholar
  • 24 Ducci K, Grotti S, Falsini G. , 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 (05) 4814-4816
    CrossrefPubMedGoogle Scholar
  • 25 Bellemain-Appaix A, O'Connor SA, Silvain J. , et al; ACTION Group. Association of clopidogrel pretreatment with mortality, cardiovascular events, and major bleeding among patients undergoing percutaneous coronary intervention: a systematic review and meta-analysis. JAMA 2012; 308 (23) 2507-2516
    CrossrefPubMedGoogle Scholar
  • 26 Gurbel PA, Bliden KP, Butler K. , et al. Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: the ONSET/OFFSET study. Circulation 2009; 120 (25) 2577-2585
    CrossrefPubMedGoogle Scholar
  • 27 Angiolillo DJ, Saucedo JF, Deraad R. , et al; SWAP Investigators. Increased platelet inhibition after switching from maintenance clopidogrel to prasugrel in patients with acute coronary syndromes: results of the SWAP (SWitching Anti Platelet) study. J Am Coll Cardiol 2010; 56 (13) 1017-1023
    CrossrefPubMedGoogle Scholar
  • 28 Diodati JG, Saucedo JF, French JK. , et al. Effect on platelet reactivity from a prasugrel loading dose after a clopidogrel loading dose compared with a prasugrel loading dose alone: Transferring From Clopidogrel Loading Dose to Prasugrel Loading Dose in Acute Coronary Syndrome Patients (TRIPLET): a randomized controlled trial. Circ Cardiovasc Interv 2013; 6 (05) 567-574
    CrossrefPubMedGoogle Scholar
  • 29 Montalescot G, van 't Hof AW, Lapostolle F. , et al; ATLANTIC Investigators. Prehospital ticagrelor in ST-segment elevation myocardial infarction. N Engl J Med 2014; 371 (11) 1016-1027
    CrossrefPubMedGoogle Scholar
  • 30 De Luca L, Capranzano P, Patti G, Parodi G. Switching of platelet P2Y12 receptor inhibitors in patients with acute coronary syndromes undergoing percutaneous coronary intervention: review of the literature and practical considerations. Am Heart J 2016; 176: 44-52
    CrossrefPubMedGoogle Scholar
  • 31 Tantry US, Bonello L, Aradi D. , et al; Working Group on On-Treatment Platelet Reactivity. Consensus and update on the definition of on-treatment platelet reactivity to adenosine diphosphate associated with ischemia and bleeding. J Am Coll Cardiol 2013; 62 (24) 2261-2273
    CrossrefPubMedGoogle Scholar
  • 32 Aradi D, Kirtane A, Bonello L. , et al. Bleeding and stent thrombosis on P2Y12-inhibitors: collaborative analysis on the role of platelet reactivity for risk stratification after percutaneous coronary intervention. Eur Heart J 2015; 36 (27) 1762-1771
    CrossrefPubMedGoogle Scholar
  • 33 Bagai A, Peterson ED, Honeycutt E. , et al. In-hospital switching between adenosine diphosphate receptor inhibitors in patients with acute myocardial infarction treated with percutaneous coronary intervention: insights into contemporary practice from the TRANSLATE-ACS study. Eur Heart J Acute Cardiovasc Care 2015; 4 (06) 499-508
    CrossrefPubMedGoogle Scholar
  • 34 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
    CrossrefPubMedGoogle Scholar
  • 35 Pareek M, Bhatt DL. Ticagrelor for patients with acute coronary syndromes: PLATOnic affair or lasting SWEDEHEART?. Eur Heart J 2016; 37 (44) 3343-3346
    CrossrefPubMedGoogle Scholar
  • 36 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 (04) 459-466
    CrossrefPubMedGoogle Scholar
  • 37 Bhatt DL, Drozda Jr JP, Shahian DM. , et al. ACC/AHA/STS statement on the future of registries and the performance measurement enterprise: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures and The Society of Thoracic Surgeons. J Am Coll Cardiol 2015; 66 (20) 2230-2245
    CrossrefPubMedGoogle Scholar
  • 38 Cuisset T, Deharo P, Quilici J. , et al. Benefit of switching dual antiplatelet therapy after acute coronary syndrome: the TOPIC (timing of platelet inhibition after acute coronary syndrome) randomized study. Eur Heart J 2017; 38 (41) 3070-3078
    CrossrefPubMedGoogle Scholar
  • 39 Sibbing D, Aradi D, Jacobshagen C. , et al; TROPICAL-ACS Investigators. Guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention (TROPICAL-ACS): a randomised, open-label, multicentre trial. Lancet 2017; 390 (10104): 1747-1757
    CrossrefPubMedGoogle Scholar
  • 40 Motovska Z, Hlinomaz O, Kala P. , et al. One-year outcomes of prasugrel versus ticagrelor in acute myocardial infarction treated with primary angioplasty: the PRAGUE-18 Study. J Am Coll Cardiol 2017
    PubMedGoogle Scholar
  • 41 Franchi F, Rollini F. De-escalation of platelet P2Y12 receptor inhibiting therapy after percutaneous coronary intervention: does one size fit all?. JACC Cardiovasc Interv 2017; 10 (24) 2571-2573
    CrossrefPubMedGoogle Scholar
  • 42 Angiolillo DJ, Rollini F, Storey RF. , et al. International expert consensus on switching platelet P2Y12 receptor-inhibiting therapies. Circulation 2017; 136 (20) 1955-1975
    CrossrefPubMedGoogle Scholar