Advertisement

American Journal of Cardiovascular Drugs

, Volume 19, Issue 4, pp 381–391 | Cite as

Real-World Data of Prasugrel vs. Ticagrelor in Acute Myocardial Infarction: Results from the RENAMI Registry

  • Ovidio De Filippo
  • Martina CorteseEmail author
  • Fabrizio D´Ascenzo
  • Sergio Raposeiras-Roubin
  • Emad Abu-Assi
  • Tim Kinnaird
  • Albert Ariza-Solé
  • Sergio Manzano-Fernández
  • Christian Templin
  • Lazar Velicki
  • Ioanna Xanthopoulou
  • Enrico Cerrato
  • Andrea Rognoni
  • Giacomo Boccuzzi
  • Antonio Montefusco
  • Andrea Montabone
  • Salma Taha
  • Alessandro Durante
  • Sebastiano Gili
  • Giulia Magnani
  • Michele Autelli
  • Alberto Grosso
  • Pedro Flores Blanco
  • Alberto Garay
  • Giorgio Quadri
  • Ferdinando Varbella
  • Berenice Caneiro Queija
  • Rafael Cobas Paz
  • María Cespón Fernández
  • Isabel Muñoz Pousa
  • Diego Gallo
  • Umberto Morbiducci
  • Alberto Dominguez-Rodriguez
  • Mariano Valdés
  • Angel Cequier
  • Dimitrios Alexopoulos
  • Andrés Iñiguez-Romo
  • Mauro Rinaldi
Original Research Article

Abstract

Background

Limited data are available concerning differences in clinical outcomes for real-life patients treated with ticagrelor versus prasugrel after percutaneous coronary intervention (PCI).

Objective

Our objective was to determine and compare the efficacy and safety of ticagrelor and prasugrel in a real-world population.

Methods

RENAMI was a retrospective, observational registry including the data and outcomes of consecutive patients with acute coronary syndrome (ACS) who underwent primary PCI and were discharged with dual antiplatelet therapy (DAPT) between January 2012 and January 2016. The mean follow-up period was 17 ± 9 months. In total, 11 university hospitals from six European countries participated. After propensity-score matching, there were no substantial differences in the baseline clinical and interventional features. All patients were treated with acetylsalicylic acid plus prasugrel 10 mg once daily or acetylsalicylic acid plus ticagrelor 90 mg twice daily. Mean duration of DAPT was 12.04 ± 3.4 months with prasugrel and 11.90 ± 4.1 months with ticagrelor (p = 0.47). The primary and secondary endpoints were long-term net adverse clinical events (NACE) and major adverse cardiovascular events (MACE), respectively, along with their single components. Subgroup analysis for freedom from NACE and MACE was performed according to length of DAPT and clinical presentation [ST-elevation myocardial infarction (STEMI)-ACS versus non-ST-elevation myocardial infarction (NSTEMI)-ACS].

Results

In total, 4424 patients (2725 ticagrelor, 1699 prasugrel) were enrolled. After propensity-score matching, 1290 patients in each cohort were included in the analysis. At 12 months, the incidence of both NACE and MACE was lower with prasugrel (NACE: 5.3% vs. 8.5% [p = 0.001]; MACE: 5% vs. 8.1% [p =  0.001]) mainly driven by a reduction in recurrent myocardial infarction (MI) (2.4 vs. 4.0%; p = 0.029) and a lower rate of Bleeding Academic Research Consortium (BARC) 3–5 bleeding (1.5 vs. 2.9%; p = 0.011). The benefit of prasugrel was confirmed for patients with NSTEMI and for those discharged with a DAPT regimen of ≤ 12 months. Only a trend in the reduction of NACE and MACE was noted for STEMI or for those treated with longer DAPT.

Conclusions

Comparison of these drugs suggested that prasugrel is safer and more efficacious than ticagrelor in combination with aspirin after NSTEMI but not STEMI. No differences were found for events occurring after 12 months. The nonrandomized design of the present research means further studies are required to support these findings.

Notes

Compliance with Ethical Standards

Funding

No external funding was used in the preparation of this manuscript.

Conflict of Interest

Ovidio De Filippo, Martina Cortese, Fabrizio D´Ascenzo, Sergio Raposeiras-Roubin, Emad Abu-Assi, Tim Kinnaird, Albert Ariza-Solé, Sergio Manzano-Fernández, Christian Templin Prof, Lazar Velicki, Ioanna Xanthopoulou, Enrico Cerrato, Andrea Rognoni, Giacomo Boccuzzi, Antonio Montefusco, Andrea Montabone, Salma Taha, Alessandro Durante, Sebastiano Gili, Giulia Magnani, Michele Autelli, Alberto Grosso, Pedro Flores Blanco, Alberto Garay, Giorgio Quadri, Ferdinando Varbella, Berenice Caneiro Queija, Rafael Cobas Paz, María Cespón Fernández, Isabel Muñoz Pousa, Diego Gallo, Umberto Morbiducci, Alberto Dominguez-Rodriguez, Mariano Valdés, Angel Cequier, Dimitrios Alexopoulos, Andrés Iñiguez-Romo, Mauro Rinaldi Prof have no potential conflicts of interest that might be relevant to the contents of this manuscript.

Supplementary material

40256_2019_339_MOESM1_ESM.doc (205 kb)
Supplementary material 1 (DOC 195 kb)

References

  1. 1.
    Abu-Assi E, Raposeiras-Roubín S, García-Acuña JM, González-Juanatey JR. Bleeding risk stratification in an era of aggressive management of acute coronary syndromes. World J Cardiol. 2014;6(11):1140–8.CrossRefGoogle Scholar
  2. 2.
    Gong IY, Goodman SG, Brieger D, Gale CP, Chew DP, Welsh RC, Huynh T, DeYoung JP, Baer C, Gyenes GT, Udell JA, Fox KAA, Yan AT. Canadian GRACE/GRACE-2 and CANRACE Investigators. GRACE risk score: Sex-based validity of in-hospital mortality prediction in Canadian patients with acute coronary syndrome. Int J Cardiol. 2017;244:24–9.CrossRefGoogle Scholar
  3. 3.
    Cordeiro F, Mateus PS, Ferreira A, Leao S, Moz M, Moreira JI, investigators of the Portuguese Registry of Acute Coronary Syndromes (ProACS). Short-term prognostic effect of prior cerebrovascular and peripheral artery disease in patients with acute coronary syndrome: Can we do better? Eur Heart J Acute Cardiovasc Care. 2017;1:2048872617716388.Google Scholar
  4. 4.
    Moretti C, Quadri G, D’Ascenzo F, Bertaina M, Giusto F, Marra S, Moiraghi C, Scaglione L, Torchio M, Montrucchio G, Bo M, Porta M, Cavallo Perin P, Marinone C, Riccardini F, Iqbal J, Omedè P, Bergerone S, Veglio F, Gaita F. THE STORM (acute coronary Syndrome in paTients end Of life and Risk assesMent) study. Emerg Med J. 2016;33(1):10–6.CrossRefGoogle Scholar
  5. 5.
    D’Ascenzo F, Iannaccone M, De Filippo O, Leone AM, Niccoli G, Zilio F, Ugo F, Cerrato E, Fineschi M, Mancone M, Rigattieri S, Amabile N, Ferlini M, Sardella G, Cresti A, Barbero U, Motreff P, Colombo F, Colangelo S, Garbo R, Biondi-Zoccai G, Tamburino C, Montefusco A, Omedè P, Moretti C, D’amico M, Souteyrand G, Gaita F, Limbruno U, Picchi A. Optical coherence tomography compared with fractional flow reserve guided approach in acute coronary syndromes: A propensity matched analysis. Int J Cardiol. 2017; 244:54–58.CrossRefGoogle Scholar
  6. 6.
    Hoedemaker NPG, Damman P, Woudstra P, Hirsch A, Windhausen F, Tijssen JGP, de Winter RJ; ICTUS Investigators. early invasive versus selective strategy for non-ST-segment elevation acute coronary syndrome: the ICTUS Trial. J Am Coll Cardiol. 2017; 69(15):1883–1893.Google Scholar
  7. 7.
    Quadri G, D Ascenzo F, Moretti C, D’Amico M, Raposeiras-Roubín S, Abu-Assi E, Henriques JP, Saucedo J, González-Juanatey JR, Wilton SB, Kikkert WJ, Nuñez-Gil I, Ariza-Sole A, Song X, Alexopoulos D, Liebetrau C, Kawaji T, Huczek Z, Nie SP, Fujii T, Correia L, Kawashiri MA, García-Acuña JM, Southern D, Alfonso E, Terol B, Garay A, Zhang D, Chen Y, Xanthopoulou I, Osman N, Möllmann H, Shiomi H, Omedè P, Montefusco A, Giordana F, Scarano S, Kowara M, Filipiak K, Wang X, Yan Y, Fan JY, Ikari Y, Nakahashi T, Sakata K, Yamagishi M, Kalpak O, Kedev S, Varbella F, Gaita F. Complete or incomplete coronary revascularization in patients with myocardial infarction and multivessel disease. A propensity score analysis from the “real life” BleeMACS (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome) registry. EuroIntervention. 2017; 13(4):407–414.CrossRefGoogle Scholar
  8. 8.
    D’Ascenzo F, Colombo F, Barbero U, Moretti C, Omedè P, Reed MJ, Tarantini G, Frati G, Di Nicolantonio JJ, Biondi Zoccai G, Gaita F. Discontinuation of dual antiplatelet therapy over 12 months after acute coronary syndromes increases risk for adverse events in patients treated with percutaneous coronary intervention: systematic review and meta-analysis. J Interv Cardiol. 2014;27(3):233–41.CrossRefGoogle Scholar
  9. 9.
    Piccolo R, Gargiulo G, Franzone A, Santucci A, Ariotti S, Baldo A, Tumscitz C, Moschovitis A, Windecker S, Valgimigli M. Use of the dual-antiplatelet therapy score to guide treatment duration after percutaneous coronary intervention. Ann Intern Med. 2017;167(1):17–25.CrossRefGoogle Scholar
  10. 10.
    D’Ascenzo F, Moretti C, Bianco M, Bernardi A, Taha S, Cerrato E, Omedè P, Montefusco A, Frangieh AH, Lee CW, Campo G, Chieffo A, Quadri G, Pavani M, Zoccai GB, Gaita F, Park SJ, Colombo A, Templin C, Lüscher TF, Stone GW. Meta-analysis of the duration of dual antiplatelet therapy in patients treated with second-generation drug-eluting stents. Am J Cardiol. 2016;117(11):1714–23.CrossRefGoogle Scholar
  11. 11.
    Costa F, Vranckx P, Leonardi S, Moscarella E, Ando G, Calabro P, Oreto G, Zijlstra F, Valgimigli M. Impact of clinical presentation on ischaemic and bleeding outcomes in patients receiving 6- or 24-month duration of dual-antiplatelet therapy after stent implantation: a pre-specified analysis from the PRODIGY (Prolonging Dual-Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia) trial. Eur Heart J. 2015;36(20):1242–51.CrossRefGoogle Scholar
  12. 12.
    Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, Neumann FJ, Ardissino D, De Servi S, Murphy SA, Riesmeyer J, Weerakkody G, Gibson CM, Antman EM; TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357(20):2001–15.CrossRefGoogle Scholar
  13. 13.
    Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA; PLATO Investigators, Freij A, Thorsén M. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361(11):1045–57.CrossRefGoogle Scholar
  14. 14.
    Bonaca MP, Wiviott SD. Prasugrel Versus ticagrelor: uncertainty remains. Circulation. 2016;134(21):1613–6.CrossRefGoogle Scholar
  15. 15.
    Lee YS, Jin CD, Kim MH, Guo LZ, Cho YR, Park K, Park JS, Park TH, Kim YD. Comparison of prasugrel and ticagrelor antiplatelet effects in korean patients presenting with ST-segment elevation myocardial infarction. Circ J. 2015;79(6):1248–54.CrossRefGoogle Scholar
  16. 16.
    Motovska Z, Hlinomaz O, Miklik R, Hromadka M, Varvarovsky I, Dusek J, Knot J, Jarkovsky J, Kala P, Rokyta R, Tousek F, Kramarikova P, Majtan B, Simek S, Branny M, Mrozek J, Cervinka P, Ostransky J, Widimsky P; PRAGUE-18 Study Group. Prasugrel versus ticagrelor in patients with acute myocardial infarction treated with primary percutaneous coronary intervention: multicenter randomized PRAGUE-18 study. Circulation. 2016;134(21):1603–12.CrossRefGoogle Scholar
  17. 17.
    Yudi MB, Clark DJ, Farouque O, Eccleston D, Andrianopoulos N, Duffy SJ, Brennan A, Lefkovits J, Ramchand J, Yip T, Oqueli E, Reid CM, Ajani AE; Melbourne Interventional Group. Clopidogrel, prasugrel or ticagrelor in patients with acute coronary syndromes undergoing percutaneous coronary intervention. Intern Med J. 2016;46(5):559–65.CrossRefGoogle Scholar
  18. 18.
    Larmore C, Effron MB, Molife C, DeKoven M, Zhu Y, Lu J, Karkare S, Lieu HD, Lee WC, Vetrovec GW. “Real-World” comparison of prasugrel with ticagrelor in patients with acute coronary syndrome treated with percutaneous coronary intervention in the United States. Catheter Cardiovasc Interv. 2016;88(4):535–44.CrossRefGoogle Scholar
  19. 19.
    Schulz S, Angiolillo DJ, Antoniucci D, Bernlochner I, Hamm C, Jaitner J, Laugwitz KL, Mayer K, von Merzljak B, Morath T, Neumann FJ, Richardt G, Ruf J, Schömig G, Schühlen H, Schunkert H, Kastrati A; Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT) 5 Trial Investigators. Randomized comparisonof ticagrelor versus prasugrel in patients with acute coronary syndrome and planned invasive strategy—design and rationale of intracoronary stenting and Antithrombotic regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT) 5 Trial. J Cardiovasc Transl Res. 2014;7(1):91–100.Google Scholar
  20. 20.
    Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2018;39(2):119–77.CrossRefGoogle Scholar
  21. 21.
    Roffi M, Patrono C, Collet J-P, Mueller C, Valgimigli M, Andreotti F, et al. 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.CrossRefGoogle Scholar
  22. 22.
    Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD, et al. Third universal definition of myocardial infarction. J Am Coll Cardiol. 2012;60:1581–98.CrossRefGoogle Scholar
  23. 23.
    D’Ascenzo F, Cavallero E, Biondi-Zoccai G, Moretti C, Omede P, Bollati M, Castagno D, Modena MG, Gaita F, Sheiban I. Use and misuse of multivariable approaches in interventional cardiology studies on drug-eluting stents: a systematic review. J Interv Cardiol. 2012;25(6):611–2.CrossRefGoogle Scholar
  24. 24.
    Levine GN, Bates ER, Bittl JA, Brindis RG, Fihn SD, Fleisher LA, Granger CB, Lange RA, Mack MJ, Mauri L, Mehran R, Mukherjee D, Newby LK, O’Gara PT, Sabatine MS, Smith PK, Smith SC Jr. 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: a Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention, 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery, 2012 ACC/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease, 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction, 2014 AHA/ACC Guideline for the Management of Patients With Non-ST-Elevation Acute Coronary Syndromes, and 2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery. Circulation. 2016;134(10):e123–55.CrossRefGoogle Scholar
  25. 25.
    Simeone JC, Molife C, Marrett E, Frech-Tamas F, Effron MB, Nordstrom BL1, Zhu YE4, Keller S, Murphy BR, Nair KV, Vetrovec GW, Page RL 2nd, McCollam PL. One-year post-discharge resource utilization and treatment patterns of patients with acute coronary syndrome managed with percutaneous coronary intervention and treated with ticagrelor or prasugrel. Am J Cardiovasc Drugs. 2015;15(5):337–50.CrossRefGoogle Scholar
  26. 26.
    Biondi-Zoccai G, Lotrionte M, Agostoni P, Abbate A, Romagnoli E, Sangiorgi G, Angiolillo DJ, Valgimigli M, Testa L, Gaita F, Sheiban I. Adjusted indirect comparison meta-analysis of prasugrel versus ticagrelor for patients with acute coronary syndromes. Int J Cardiol. 2011;150(3):325–31.CrossRefGoogle Scholar
  27. 27.
    Chatterjee S, Ghose A, Sharma A, Guha G, Mukherjee D, Frankel R. Comparing newer oral anti-platelets prasugrel and ticagrelor in reduction of ischemic events-evidence from a network meta-analysis. J Thromb Thrombolysis. 2013;36(3):223–32.CrossRefGoogle Scholar
  28. 28.
    Ferrara LA, Russo BF, Gente R, Esposito G, Rapacciuolo A, de Simone G, STEMI and NSTEMI: a mono versus a multivessel disease? Int J Cardiol. 2013; 168(3):2905–6.CrossRefGoogle Scholar
  29. 29.
    Li YG, Ni L, Brandt JT, Small DS, Payne CD, Ernest CS 2nd, Rohatagi S, Farid NA, Jakubowski JA, Winters KJ. Inhibition of platelet aggregation with prasugrel and clopidogrel: an integrated analysis in 846 subjects. Platelets. 2009;20(5):316–27.CrossRefGoogle Scholar
  30. 30.
    Storey RF, Husted S, Harrington RA, Heptinstall S, Wilcox RG, Peters G, Wickens M, Emanuelsson H, Gurbel P, Grande P, Cannon CP. Inhibition of platelet aggregation by AZD6140, a reversible oral P2Y12 receptor antagonist, compared with clopidogrel in patients with acute coronary syndromes J Am Coll Cardiol. 2007;50(19):1852–6.CrossRefGoogle Scholar
  31. 31.
    Storey RF, Angiolillo DJ, Patil SB, Desai B, Ecob R, Husted S, Emanuelsson H, Cannon CP, Becker RC, Wallentin L. Inhibitory effects of ticagrelor compared with clopidogrel on platelet function in patients with acute coronary syndromes: the PLATO (PLATelet inhibition and patient Outcomes) PLATELET substudy. J Am Coll Cardiol. 2010;56(18):1456–62.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

corrected publication 2019

Authors and Affiliations

  • Ovidio De Filippo
    • 1
  • Martina Cortese
    • 1
    Email author
  • Fabrizio D´Ascenzo
    • 1
  • Sergio Raposeiras-Roubin
    • 2
  • Emad Abu-Assi
    • 2
  • Tim Kinnaird
    • 3
  • Albert Ariza-Solé
    • 4
  • Sergio Manzano-Fernández
    • 5
  • Christian Templin
    • 6
  • Lazar Velicki
    • 7
    • 8
  • Ioanna Xanthopoulou
    • 9
  • Enrico Cerrato
    • 10
  • Andrea Rognoni
    • 11
  • Giacomo Boccuzzi
    • 12
  • Antonio Montefusco
    • 1
  • Andrea Montabone
    • 12
  • Salma Taha
    • 13
  • Alessandro Durante
    • 14
  • Sebastiano Gili
    • 6
  • Giulia Magnani
    • 6
  • Michele Autelli
    • 1
  • Alberto Grosso
    • 1
  • Pedro Flores Blanco
    • 5
  • Alberto Garay
    • 4
  • Giorgio Quadri
    • 10
  • Ferdinando Varbella
    • 10
  • Berenice Caneiro Queija
    • 2
  • Rafael Cobas Paz
    • 2
  • María Cespón Fernández
    • 2
  • Isabel Muñoz Pousa
    • 2
  • Diego Gallo
    • 15
  • Umberto Morbiducci
    • 15
  • Alberto Dominguez-Rodriguez
    • 16
  • Mariano Valdés
    • 5
  • Angel Cequier
    • 4
  • Dimitrios Alexopoulos
    • 9
  • Andrés Iñiguez-Romo
    • 2
  • Mauro Rinaldi
    • 1
  1. 1.Department of Cardiology, Department of Medical SciencesUniversity of TorinoTurinItaly
  2. 2.Department of CardiologyUniversity Hospital Álvaro CunqueiroVigoSpain
  3. 3.Cardiology DepartmentUniversity Hospital of WalesCardiffUK
  4. 4.Department of CardiologyUniversity Hospital de BellvitgeBarcelonaSpain
  5. 5.Department of CardiologyUniversity Hospital Virgen ArrixacaMurciaSpain
  6. 6.Department of Cardiology, University Heart CenterUniversity Hospital ZurichZurichSwitzerland
  7. 7.Faculty of MedicineUniversity of Novi SadNovi SadSerbia
  8. 8.Institute for Cardiovascular Diseases of VojvodinaSremska KamenicaSerbia
  9. 9.University Patras HospitalAthensGreece
  10. 10.Interventional Unit, San Luigi Gonzaga University HospitalOrbassano and Infermi HospitalRivoli (Torino)Italy
  11. 11.Catheterization LaboratoryMaggiore della Carità HospitalNovaraItaly
  12. 12.Department of CardiologyS.G. Bosco HospitalTurinItaly
  13. 13.Department of Cardiology, Faculty of MedicineAssiut UniversityAsyutEgypt
  14. 14.U.O. Cardiologia, Ospedale ValduceComoItaly
  15. 15.PolitoBIOMed Lab, Department of Mechanical and Aerospace EngineeringPolitecnico di TorinoTurinItaly
  16. 16.Department of CardiologyUniversity Hospital from CanariasTenerifeSpain

Personalised recommendations