Skip to main content
Top
Published in: Journal of Thrombosis and Thrombolysis 3/2021

Open Access 01-04-2021 | Ticagrelor

Use of the VerifyNow point of care assay to assess the pharmacodynamic effects of loading and maintenance dose regimens of prasugrel and ticagrelor

Authors: Dominick J. Angiolillo, Latonya Been, Marc Rubinstein, Michael Martin, Fabiana Rollini, Francesco Franchi

Published in: Journal of Thrombosis and Thrombolysis | Issue 3/2021

Login to get access

Abstract

Prasugrel and ticagrelor are potent oral platelet P2Y12 inhibitors and are recommended over clopidogrel in patients with acute coronary syndrome (ACS). Oral platelet P2Y12 inhibitors are characterized by varying degrees of pharmacodynamic response profiles as assessed by a variety of commercially available assays. Because of its ease of use, rapid turnaround times and ability to provide results specific to P2Y12 inhibitory effects, VerifyNow has emerged as one of the most commonly utilized platelet function assays. However, reference ranges with VerifyNow have been reported mainly for clopidogrel and there has not yet been any study specifically conducted to provide the expected on treatment reference ranges following administration of prasugrel and ticagrelor. This was a prospective single center investigation conducted in 120 patients with ACS who were treated with prasugrel or ticagrelor as per standard of care. Patients who underwent percutaneous coronary interventions (PCI) were treated with a loading dose of prasugrel (60 mg) or ticagrelor (180 mg), and patients who were on maintenance therapy were taking prasugrel (10 mg qd or 5 mg qd) or ticagrelor (90 mg bid). Platelet function testing was performed using the VerifyNow™ PRUTest™. The overall range of PRUTest values was lower than that observed in studies of patients treated with clopidogrel. The use of a maintenance dose regimen had a wider range of PRUTest values compared to the use of a loading dose for both prasugrel (1–179 vs. 2–128) and ticagrelor (1–196 vs. 1–177). The average PRUTest values in patients on prasugrel and ticagrelor maintenance dosing were 20% and 9% higher those observed in patients treated with a loading dose. PRUTest results following loading dose administration were very similar between drugs, but were 20% higher with prasugrel compared with ticagrelor during maintenance dosing. This study establishes expected PRUTest ranges for patients taking loading and maintenance doses of prasugrel and ticagrelor.
Clinical Trial Registration http://​www.​clinicaltrials.​gov Unique Identifier: NCT04492423, registered July 2020 retrospectively registered.
Literature
1.
go back to reference Capodanno D, Alfonso F, Levine GN, Valgimigli M, Angiolillo DJ (2018) ACC/AHA Versus ESC Guidelines on Dual Antiplatelet Therapy: JACC Guideline Comparison. J Am Coll Cardiol 72(23 Pt A):2915–2931CrossRef Capodanno D, Alfonso F, Levine GN, Valgimigli M, Angiolillo DJ (2018) ACC/AHA Versus ESC Guidelines on Dual Antiplatelet Therapy: JACC Guideline Comparison. J Am Coll Cardiol 72(23 Pt A):2915–2931CrossRef
2.
go back to reference Franchi F, Angiolillo DJ (2015) Novel antiplatelet agents in acute coronary syndrome. Nat Rev Cardiol 12:30–47CrossRef Franchi F, Angiolillo DJ (2015) Novel antiplatelet agents in acute coronary syndrome. Nat Rev Cardiol 12:30–47CrossRef
3.
go back to reference Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, Alfonso F, Macaya C, Bass TA, Costa MA (2007) Variability in individual responsiveness to clopidogrel: clinical implications, management, and future perspectives. J Am Coll Cardiol 49:1505–1516CrossRef Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, Alfonso F, Macaya C, Bass TA, Costa MA (2007) Variability in individual responsiveness to clopidogrel: clinical implications, management, and future perspectives. J Am Coll Cardiol 49:1505–1516CrossRef
4.
go back to reference Sibbing D, Aradi D, Alexopoulos D, Ten Berg J, Bhatt DL, Bonello L, Collet JP, Cuisset T, Franchi F, Gross L, Gurbel P, Jeong YH, Mehran R, Moliterno DJ, Neumann FJ, Pereira NL, Price MJ, Sabatine MS, So DYF, Stone GW, Storey RF, Tantry U, Trenk D, Valgimigli M, Waksman R, Angiolillo DJ (2019) Updated expert consensus statement on platelet function and genetic testing for guiding P2Y12 receptor inhibitor treatment in percutaneous coronary intervention. JACC Cardiovasc Interv 12:1521–1537CrossRef Sibbing D, Aradi D, Alexopoulos D, Ten Berg J, Bhatt DL, Bonello L, Collet JP, Cuisset T, Franchi F, Gross L, Gurbel P, Jeong YH, Mehran R, Moliterno DJ, Neumann FJ, Pereira NL, Price MJ, Sabatine MS, So DYF, Stone GW, Storey RF, Tantry U, Trenk D, Valgimigli M, Waksman R, Angiolillo DJ (2019) Updated expert consensus statement on platelet function and genetic testing for guiding P2Y12 receptor inhibitor treatment in percutaneous coronary intervention. JACC Cardiovasc Interv 12:1521–1537CrossRef
5.
go back to reference 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 (2007) Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 357:2001–2015CrossRef 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 (2007) Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 357:2001–2015CrossRef
6.
go back to reference 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 (2009) Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 361:1045–1057CrossRef 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 (2009) Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 361:1045–1057CrossRef
7.
go back to reference Michelson AD (2009) Methods for the measurement of platelet function. Am J Cardiol 103:20A-26ACrossRef Michelson AD (2009) Methods for the measurement of platelet function. Am J Cardiol 103:20A-26ACrossRef
8.
go back to reference Malinin A, Pokov A, Spergling M, Defranco A, Schwartz K, Schwartz D, Mahmud E, Atar D, Serebruany V (2007) Monitoring platelet inhibition after clopidogrel with the VerifyNow-P2Y12(R) rapid analyzer: the VERIfy Thrombosis risk ASsessment (VERITAS) study. Thromb Res 119:277–284CrossRef Malinin A, Pokov A, Spergling M, Defranco A, Schwartz K, Schwartz D, Mahmud E, Atar D, Serebruany V (2007) Monitoring platelet inhibition after clopidogrel with the VerifyNow-P2Y12(R) rapid analyzer: the VERIfy Thrombosis risk ASsessment (VERITAS) study. Thromb Res 119:277–284CrossRef
10.
go back to reference Storey RF (2006) Biology and pharmacology of the platelet P2Y12 receptor. Curr Pharm Des 12:1255–1259CrossRef Storey RF (2006) Biology and pharmacology of the platelet P2Y12 receptor. Curr Pharm Des 12:1255–1259CrossRef
11.
go back to reference Defining, establishing, and verifying reference intervals in the clinical laboratory; approved guideline, CLSI document EP28-A3, Clinical and Laboratory Standards Institute (CLSI) www.clsi.org Defining, establishing, and verifying reference intervals in the clinical laboratory; approved guideline, CLSI document EP28-A3, Clinical and Laboratory Standards Institute (CLSI) www.​clsi.​org
12.
go back to reference Bae JP, Candrilli SD, Fortenberry J, Meyers JL, Jakubowski JA, Drenning D (2014) Point-of-care platelet reactivity determination with VerifyNow-P2Y12 following administration of clopidogrel or prasugrel: data from a real-world, clinical care inpatient setting. Hosp Pract 42:7–15CrossRef Bae JP, Candrilli SD, Fortenberry J, Meyers JL, Jakubowski JA, Drenning D (2014) Point-of-care platelet reactivity determination with VerifyNow-P2Y12 following administration of clopidogrel or prasugrel: data from a real-world, clinical care inpatient setting. Hosp Pract 42:7–15CrossRef
13.
go back to reference Price MJ, Angiolillo DJ, Teirstein PS, Lillie E, Manoukian SV, Berger PB, Tanguay JF, Cannon CP, Topol EJ (2011) 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 124:1132–1137CrossRef Price MJ, Angiolillo DJ, Teirstein PS, Lillie E, Manoukian SV, Berger PB, Tanguay JF, Cannon CP, Topol EJ (2011) 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 124:1132–1137CrossRef
14.
go back to reference Stone GW, Witzenbichler B, Weisz G, Rinaldi MJ, Neumann FJ, Metzger DC, Henry TD, Cox DA, Duffy PL, Mazzaferri E, Gurbel PA, Xu K, Parise H, Kirtane AJ, Brodie BR, Mehran R, Stuckey TD (2013) Platelet reactivity and clinical outcomes after coronary artery implantation of drug-eluting stents (ADAPT-DES): a prospective multicentre registry study. Lancet 382:614–623CrossRef Stone GW, Witzenbichler B, Weisz G, Rinaldi MJ, Neumann FJ, Metzger DC, Henry TD, Cox DA, Duffy PL, Mazzaferri E, Gurbel PA, Xu K, Parise H, Kirtane AJ, Brodie BR, Mehran R, Stuckey TD (2013) Platelet reactivity and clinical outcomes after coronary artery implantation of drug-eluting stents (ADAPT-DES): a prospective multicentre registry study. Lancet 382:614–623CrossRef
15.
go back to reference Michelson AD, Frelinger AL, Braunwald E, Downey WE, Angiolillo DJ, Xenopoulos NP, Jakubowski JA, Li Y, Murphy SA, Qin J, McCabe CH, Antman EM, Wiviott SD (2009) Pharmacodynamic assessment of platelet inhibition by prasugrel vs. clopidogrel in the TRITON-TIMI 38 trial. Eur Heart J 30:1753–1763CrossRef Michelson AD, Frelinger AL, Braunwald E, Downey WE, Angiolillo DJ, Xenopoulos NP, Jakubowski JA, Li Y, Murphy SA, Qin J, McCabe CH, Antman EM, Wiviott SD (2009) Pharmacodynamic assessment of platelet inhibition by prasugrel vs. clopidogrel in the TRITON-TIMI 38 trial. Eur Heart J 30:1753–1763CrossRef
16.
go back to reference Storey RF, Angiolillo DJ, Patil SB, Desai B, Ecob R, Husted S, Emanuelsson H, Cannon CP, Becker RC, Wallentin L (2010) 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 56:1456–1462CrossRef Storey RF, Angiolillo DJ, Patil SB, Desai B, Ecob R, Husted S, Emanuelsson H, Cannon CP, Becker RC, Wallentin L (2010) 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 56:1456–1462CrossRef
17.
go back to reference Angiolillo DJ, Schneider DJ, Bhatt DL, French WJ, Price MJ, Saucedo JF, Shaburishvili T, Huber K, Prats J, Liu T, Harrington RA, Becker RC (2012) Pharmacodynamic effects of cangrelor and clopidogrel: the platelet function substudy from the cangrelor versus standard therapy to achieve optimal management of platelet inhibition (CHAMPION) trials. J Thromb Thrombol 34:44–55CrossRef Angiolillo DJ, Schneider DJ, Bhatt DL, French WJ, Price MJ, Saucedo JF, Shaburishvili T, Huber K, Prats J, Liu T, Harrington RA, Becker RC (2012) Pharmacodynamic effects of cangrelor and clopidogrel: the platelet function substudy from the cangrelor versus standard therapy to achieve optimal management of platelet inhibition (CHAMPION) trials. J Thromb Thrombol 34:44–55CrossRef
18.
go back to reference Rollini F, Franchi F, Thano E, Faz G, Park Y, Kureti M, Cho JR, Been L, Bass TA, Angiolillo DJ (2017) In vitro pharmacodynamic effects of cangrelor on platelet P2Y(12) receptor-mediated signaling in ticagrelor-treated patients. JACC Cardiovasc Interv 10:1374–1375CrossRef Rollini F, Franchi F, Thano E, Faz G, Park Y, Kureti M, Cho JR, Been L, Bass TA, Angiolillo DJ (2017) In vitro pharmacodynamic effects of cangrelor on platelet P2Y(12) receptor-mediated signaling in ticagrelor-treated patients. JACC Cardiovasc Interv 10:1374–1375CrossRef
19.
go back to reference Rollini F, Franchi F, Tello-Montoliu A, Patel R, Darlington A, Ferreiro JL, Cho JR, Muñiz-Lozano A, Desai B, Zenni MM, Guzman LA, Bass TA, Angiolillo DJ (2014) Pharmacodynamic effects of cangrelor on platelet P2Y12 receptor-mediated signaling in prasugrel-treated patients. JACC Cardiovasc Interv 7:426–434CrossRef Rollini F, Franchi F, Tello-Montoliu A, Patel R, Darlington A, Ferreiro JL, Cho JR, Muñiz-Lozano A, Desai B, Zenni MM, Guzman LA, Bass TA, Angiolillo DJ (2014) Pharmacodynamic effects of cangrelor on platelet P2Y12 receptor-mediated signaling in prasugrel-treated patients. JACC Cardiovasc Interv 7:426–434CrossRef
20.
go back to reference Franchi F, Rollini F, Rivas A, Wali M, Briceno M, Agarwal M, Shaikh Z, Nawaz A, Silva G, Been L, Smairat R, Kaufman M, Pineda AM, Suryadevara S, Soffer D, Zenni MM, Bass TA, Angiolillo DJ (2019) Platelet inhibition with cangrelor and crushed ticagrelor in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Circulation 139:1661–1670CrossRef Franchi F, Rollini F, Rivas A, Wali M, Briceno M, Agarwal M, Shaikh Z, Nawaz A, Silva G, Been L, Smairat R, Kaufman M, Pineda AM, Suryadevara S, Soffer D, Zenni MM, Bass TA, Angiolillo DJ (2019) Platelet inhibition with cangrelor and crushed ticagrelor in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Circulation 139:1661–1670CrossRef
21.
go back to reference Jernberg T, Payne CD, Winters KJ, Darstein C, Brandt JT, Jakubowski JA, Naganuma H, Siegbahn A, Wallentin L (2006) 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 27:1166–1173CrossRef Jernberg T, Payne CD, Winters KJ, Darstein C, Brandt JT, Jakubowski JA, Naganuma H, Siegbahn A, Wallentin L (2006) 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 27:1166–1173CrossRef
22.
go back to reference Ferreiro JL, Angiolillo DJ (2011) Diabetes and antiplatelet therapy in acute coronary syndrome. Circulation 123:798–813CrossRef Ferreiro JL, Angiolillo DJ (2011) Diabetes and antiplatelet therapy in acute coronary syndrome. Circulation 123:798–813CrossRef
23.
go back to reference Capodanno D, Angiolillo DJ (2020) Antithrombotic therapy for atherosclerotic cardiovascular disease risk mitigation in patients with coronary artery disease and diabetes mellitus. Circulation 142:2172–2188CrossRef Capodanno D, Angiolillo DJ (2020) Antithrombotic therapy for atherosclerotic cardiovascular disease risk mitigation in patients with coronary artery disease and diabetes mellitus. Circulation 142:2172–2188CrossRef
24.
go back to reference Rollini F, Franchi F, Cho JR, DeGroat C, Bhatti M, Muniz-Lozano A, Singh K, Ferrante E, Wilson RE, Dunn EC, Zenni MM, Guzman LA, Bass TA, Angiolillo DJ (2016) A head-to-head pharmacodynamic comparison of prasugrel vs. ticagrelor after switching from clopidogrel in patients with coronary artery disease: results of a prospective randomized study. Eur Heart J 37:2722–2730CrossRef Rollini F, Franchi F, Cho JR, DeGroat C, Bhatti M, Muniz-Lozano A, Singh K, Ferrante E, Wilson RE, Dunn EC, Zenni MM, Guzman LA, Bass TA, Angiolillo DJ (2016) A head-to-head pharmacodynamic comparison of prasugrel vs. ticagrelor after switching from clopidogrel in patients with coronary artery disease: results of a prospective randomized study. Eur Heart J 37:2722–2730CrossRef
25.
go back to reference Franchi F, Rollini F, Aggarwal N, Hu J, Kureti M, Durairaj A, Duarte VE, Cho JR, Been L, Zenni MM, Bass TA, Angiolillo DJ (2016) Pharmacodynamic comparison of prasugrel versus ticagrelor in patients with type 2 diabetes mellitus and coronary artery disease: the OPTIMUS (Optimizing Antiplatelet Therapy in Diabetes Mellitus)-4 study. Circulation 134:780–792CrossRef Franchi F, Rollini F, Aggarwal N, Hu J, Kureti M, Durairaj A, Duarte VE, Cho JR, Been L, Zenni MM, Bass TA, Angiolillo DJ (2016) Pharmacodynamic comparison of prasugrel versus ticagrelor in patients with type 2 diabetes mellitus and coronary artery disease: the OPTIMUS (Optimizing Antiplatelet Therapy in Diabetes Mellitus)-4 study. Circulation 134:780–792CrossRef
26.
go back to reference Franchi F, Rollini F, Angiolillo DJ (2017) Antithrombotic therapy for patients with STEMI undergoing primary PCI. Nat Rev Cardiol 14:361–379CrossRef Franchi F, Rollini F, Angiolillo DJ (2017) Antithrombotic therapy for patients with STEMI undergoing primary PCI. Nat Rev Cardiol 14:361–379CrossRef
27.
go back to reference Franchi F, Rollini F, Park Y, Hu J, Kureti M, Rivas Rios J, Faz G, Yaranov D, Been L, Pineda AM, Suryadevara S, Soffer D, Zenni MM, Bass TA, Angiolillo DJ (2019) Effects of methylnaltrexone on ticagrelor-induced antiplatelet effects in coronary artery disease patients treated with morphine. JACC Cardiovasc Interv 12:1538–1549CrossRef Franchi F, Rollini F, Park Y, Hu J, Kureti M, Rivas Rios J, Faz G, Yaranov D, Been L, Pineda AM, Suryadevara S, Soffer D, Zenni MM, Bass TA, Angiolillo DJ (2019) Effects of methylnaltrexone on ticagrelor-induced antiplatelet effects in coronary artery disease patients treated with morphine. JACC Cardiovasc Interv 12:1538–1549CrossRef
Metadata
Title
Use of the VerifyNow point of care assay to assess the pharmacodynamic effects of loading and maintenance dose regimens of prasugrel and ticagrelor
Authors
Dominick J. Angiolillo
Latonya Been
Marc Rubinstein
Michael Martin
Fabiana Rollini
Francesco Franchi
Publication date
01-04-2021
Publisher
Springer US
Published in
Journal of Thrombosis and Thrombolysis / Issue 3/2021
Print ISSN: 0929-5305
Electronic ISSN: 1573-742X
DOI
https://doi.org/10.1007/s11239-021-02386-7

Other articles of this Issue 3/2021

Journal of Thrombosis and Thrombolysis 3/2021 Go to the issue