Real-World Data of Prasugrel vs. Ticagrelor in Acute Myocardial Infarction: Results from the RENAMI Registry
Limited data are available concerning differences in clinical outcomes for real-life patients treated with ticagrelor versus prasugrel after percutaneous coronary intervention (PCI).
Our objective was to determine and compare the efficacy and safety of ticagrelor and prasugrel in a real-world population.
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].
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.
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.
Compliance with Ethical Standards
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.
- 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.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.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.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.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.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.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
- 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.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.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.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
- 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.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.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.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.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.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
- 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.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.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
- 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.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
corrected publication 2019