Ticagrelor vs prasugrel one-month maintenance therapy: Impact on platelet reactivity and bleeding events

Dimitrios Alexopoulos; Katerina Stavrou; Ioanna Koniari; Vassilios Gkizas; Angelos Perperis; Kosmas Kontoprias; Chrysoula Vogiatzi; Theodora Bampouri; Ioanna Xanthopoulou

doi:10.1160/TH14-02-0119

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2014; 112(03): 551-557
DOI: 10.1160/TH14-02-0119

Platelets and Blood Cells

Schattauer GmbH

Ticagrelor vs prasugrel one-month maintenance therapy: Impact on platelet reactivity and bleeding events

Authors

Dimitrios Alexopoulos

¹Department of Cardiology, Patras University Hospital, Rion, Patras, Greece
Katerina Stavrou

¹Department of Cardiology, Patras University Hospital, Rion, Patras, Greece
Ioanna Koniari

¹Department of Cardiology, Patras University Hospital, Rion, Patras, Greece
Vassilios Gkizas

¹Department of Cardiology, Patras University Hospital, Rion, Patras, Greece
Angelos Perperis

¹Department of Cardiology, Patras University Hospital, Rion, Patras, Greece
Kosmas Kontoprias

¹Department of Cardiology, Patras University Hospital, Rion, Patras, Greece
Chrysoula Vogiatzi

¹Department of Cardiology, Patras University Hospital, Rion, Patras, Greece
Theodora Bampouri

¹Department of Cardiology, Patras University Hospital, Rion, Patras, Greece
Ioanna Xanthopoulou

¹Department of Cardiology, Patras University Hospital, Rion, Patras, Greece

Abstract

Summary

Platelet reactivity (PR) and bleeding events following therapy with ticagrelor vs prasugrel have not been adequately studied. We aimed to compare PR and bleeding events in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) while on ticagrelor vs prasugrel for one month. Consecutive patients who were discharged either on ticagrelor 90 mg bid maintenance dose (MD) or prasugrel 10 mg MD were invited for PR assessment (VerifyNow, in PRU) at one month. High PR (HPR) was defined as >208 PRU. Bleeding events [Bleeding Academic Research Consortium (BARC) classification] were monitored. Out of 937 screened patients, 512 were analysed, 278 under ticagrelor MD and 234 under prasugrel MD. PR at 30 days (C-statistic of the propensity score model 0.63, 0.58–0.67 95% CI, p<0.001) was lower when on ticagrelor compared with prasugrel (33.3, 95% CI 29.3–37.3 vs 84.6, 95% CI 73.6–95.6, p<0.001). In the analysed population more BARC type 1 bleeding events were observed with ticagrelor compared to prasugrel (36.7% vs 28.2%, p=0.047). In 221 propensity score matched pairs, BARC type 1 bleeding rate was marginally higher in ticagrelor vs prasugrel treated patients (35.7% vs 27.1%, p=0.05). BARC type ≥2 events did not differ between groups 5 (2.3%) vs 5 (2.3%). HPR rate was higher for prasugrel-treated patients (5.4% vs 0%, p<0.001). In conclusion, in patients with ACS undergoing PCI, ticagrelor MD produces a significantly higher platelet inhibition compared to prasugrel MD. This pharmacodynamic difference might be associated with more nuisance bleeding events with ticagrelor use.

Clinical Trial Registration ClinicalTrials.gov Identifier: NCT01774955.

Keywords

Ticagrelor - prasugrel - platelet aggregation - percutaneous coronary intervention

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Referenzen

References
1 Jernberg T, Payne CD, Winters KJ. et al. Prasugrel achieves greater inhibition of platelet aggregation and a lower rate of non-responders compared with clopidogrel in aspirin-treated patients with stable coronary artery disease. Eur Heart J 2006; 27: 1166-1173.
2 Storey RF, Husted S, Harrington RA. et al. 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: 1852-1856.
3 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: 2001-2015.
4 Wallentin L, Becker RC, Budaj A. et al. PLATO Investigators. Freij A, Thorsén M. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361: 1045-1057.
5 Alexopoulos D, Galati A, Xanthopoulou I. et al. Ticagrelor versus prasugrel in acute coronary syndrome patients with high on-clopidogrel platelet reactivity following percutaneous coronary intervention: a pharmacodynamic study. J Am Coll Cardiol 2012; 60: 193-199.
6 Alexopoulos D, Xanthopoulou I, Mavronasiou E. et al. Randomized assessment of ticagrelor versus prasugrel antiplatelet effects in patients with diabetes. Diabetes Care 2013; 36: 2211-2216.
7 Laine M, Frère C, Toesca R. et al. Ticagrelor versus prasugrel in diabetic patients with an acute coronary syndrome. A pharmacodynamic randomised study. Thromb Haemost 2014; 111: 273-278.
8 Alexopoulos D, Xanthopoulou I, Gkizas V. et al. Randomized assessment of ticagrelor versus prasugrel antiplatelet effects in patients with ST-segment-elevation myocardial infarction. Circ Cardiovasc Interv 2012; 05: 797-804.
9 Parodi G, Valenti R, Bellandi B. et al. Comparison of prasugrel and ticagrelor loading doses in ST-segment elevation myocardial infarction patients: RAPID (Rapid Activity of Platelet Inhibitor Drugs) primary PCI study. J Am Coll Cardiol 2013; 61: 1601-1606.
10 Deharo P, Bassez C, Bonnet G. et al. Prasugrel versus ticagrelor in acute coronary syndrome: A randomized comparison. Int J Cardiol 2013; 170: e21-22.
11 Cattaneo M. High on-treatment platelet reactivity--definition and measurement. Thromb Haemost 2013; 109: 792-798.
12 Grove EL, Hossain R, Storey RF. Platelet function testing and prediction of procedural bleeding risk. Thromb Haemost 2013; 109: 817-824.
13 Trenk D, Kristensen SD, Hochholzer W. et al. High on-treatment platelet reactivity and P2Y12 antagonists in clinical trials. Thromb Haemost 2013; 109: 834-845.
14 Alexopoulos D, Xanthopoulou I, Stavrou K. et al. Platelet reactivity variation following ticagrelor maintenance dose may allow noncompliance diagnosis by platelet function testing. Can J Cardiol 2013; 29: 1743.e13-1743.e14.
15 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: 2736-2747.
16 Price MJ, Angiolillo DJ, Teirstein PS. et al. Platelet reactivity and cardiovascular outcomes after percutaneous coronary intervention: a time-dependent analysis of the Gauging Responsiveness with a VerifyNow P2Y12 assay: Impact on Thrombosis and Safety (GRAVITAS) trial. Circulation 2011; 124: 1132-1137.
17 Alexopoulos D, Xanthopoulou I, Siapika A. et al. Evolving pattern of on-prasugrel and on-ticagrelor platelet reactivity over time in ST elevation myocardial infarction patients. Int J Cardiol 2013; 168: 629-630.
18 Joshi RR, Hossain R, Morton AC. et al. Evolving pattern of platelet P2Y12 inhibition in patients with acute coronary syndromes. Platelets. 2013 Epub ahead of print.
19 Alexopoulos D. Prasugrel resistance: fact or fiction. Platelets 2012; 23: 83-90.
20 Kerneis M, Silvain J, Abtan J. et al. Switching acute coronary syndrome patients from prasugrel to clopidogrel. JACC Cardiovasc Interv 2013; 06: 158-165.
21 Gurbel PA, Erlinge D, Ohman EM. et al. for the TRILOGY ACS Platelet Function Substudy Investigators. Platelet Function During Extended Prasugrel and Clopidogrel Therapy for Patients With ACS Treated Without Revascularization: The TRILOGY ACS Platelet Function Substudy. J Am Med Assoc 2012; 308: 1785-1794.
22 Bliden KP, Tantry US, Storey RF. et al. The effect of ticagrelor versus clopidogrel on high on-treatment platelet reactivity: combined analysis of the ONSET/OFFSET and RESPOND studies. Am Heart J 2011; 162: 160-165.
23 Laine M, Toesca R, Berbis J. et al. Platelet reactivity evaluated with the VASP assay following ticagrelor loading dose in acute coronary syndrome patients undergoing percutaneous coronary intervention. Thromb Res 2013; 132: e15-18.
24 Cuisset T, Loosveld M, Morange PE. et al. CYP2C19*2 and *17 alleles have a significant impact on platelet response and bleeding risk in patients treated with prasugrel after acute coronary syndrome. JACC Cardiovasc Interv 2012; 05: 1280-1287.
25 Tantry US, Bliden KP, Wei C. et al. First analysis of the relation between CYP2C19 genotype and pharmacodynamics in patients treated with ticagrelor versus clopidogrel: the ONSET/OFFSET and RESPOND genotype studies. Circ Cardiovasc Genet 2010; 03: 556-566.
26 Roy P, Bonello L, Torguson R. et al. Impact of “nuisance” bleeding on clopidogrel compliance in patients undergoing intracoronary drug-eluting stent implantation. Am J Cardiol 2008; 102: 1614-1617.
27 Armero S, Bonello L, Berbis J. et al. Rate of nuisance bleedings and impact on compliance to prasugrel in acute coronary syndromes. Am J Cardiol 2011; 108: 1710-1713.
28 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 ADP Associated with Ischemia and Bleeding. J Am Coll Cardiol 2013; 62: 2261-2273.
29 Cayla G, Cuisset T, Silvain J. et al. Prasugrel monitoring and bleeding in real world patients. Am J Cardiol 2013; 111: 38-44.
30 Cuisset T, Grosdidier C, Loundou AD. et al. Clinical implications of very low on-treatment platelet reactivity in patients treated with thienopyridine: the POBA study (predictor of bleedings with antiplatelet drugs). JACC Cardiovasc Interv 2013; 06: 854-863.
31 Bonello L, Mancini J, Pansieri M. et al. Relationship between post-treatment platelet reactivity and ischemic and bleeding events at 1-year follow-up in patients receiving prasugrel. J Thromb Haemost 2012; 10: 1999-2005.

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