The role of prasugrel in modern cardiological therapy Review article
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Published:
Jun 30, 2010
Keywords:
antiplatelet therapy, thienopyridine, P2Y12 receptor, ADP receptor, prasugrel
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Abstract
As aberrant platelet activation underlies intra-arterial thrombus formation, dual antiplatelet therapy – of aspirin and clopidogrel – has become a mainstay of treatment of acute coronary thrombosis. Two complementary yet independent mechanisms of blocking platelet activation and aggregation have proven to be clinically beneficial in preventing atherothrombotic complications, including myocardial infarction (MI), stroke, vascular death, as well as stent-associated thrombosis. Nonetheless, the combination of aspirin and clopidogrel has its drawbacks, and recurrent atherothrombotic events occur in patients receiving this dual antiplatelet therapy. Of note is the phenomenon of so-called resistance, also known as hyporesponsiveness, to aspirin and/or clopidogrel, as this predisposes to recurrent cardiovascular events. Other limitations of clopidogrel include its modest level platelet inhibition, a wide variability in patient response and delayed onset of action. Prasugrel, which is a new member of the thienopyridine antiplatelet agents, is able to overcome these shortcomings of clopidogrel. It is 10 times more potent, has a rapid onset, and is not as influenced by drug interactions nor genetic polymorphisms of cytochrome enzymes; thus prasugrel results in a faster, higher and more consistent level of platelet inhibition. Clinically this translates into a reduction in thrombo-occlusive events, but also an increased bleeding risk. This paper reviews the available pharmacological and clinical data on prasugrel and clarifies the current place of prasugrel in the management of arterial coronary thrombosis.
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Postuła , M. (2010). The role of prasugrel in modern cardiological therapy. Cardiology in Practice, 4(2), 62-68. Retrieved from https://journalsmededu.pl/index.php/kwp/article/view/1636
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References
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13. Brandt J.T., Payne C.D., Wiviott S.D. et al.: A comparison of prasugrel and clopidogrel loading doses on platelet function: Magnitude of platelet inhibition is related to active metabolite formation. Am. Heart J. 2007, 153: 9-16.
14. Brandt J.T., Close S.L., Iturria S.J. et al.: Common polymorphisms of CYP2C19 and CYP2C9 affect the pharmacokinetic and pharmacodynamic response to clopidogrel but not prasugrel. J. Thromb. Haemost. 2007, 5: 2429-2436.
15. Mega J.L., Close S.L., Wiviott S.D. et al.: Cytochrome P-450 polymorphisms and response to clopidogrel. N. Engl. J. Med. 2009, 360: 354-362.
16. Juurlink D.N., Gomes T., Ko D.T. et al.: A population based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ. 2009, 180: 713-718.
17. Lau W.C., Waskell L.A., Watkins P.B. et al.: Atorvastatin reduces the ability of clopidogrel to inhibit platelet aggregation: a new drug-drug interaction. Circulation 2003, 107: 32-37.
18. Farid N.A., Small D.S., Payne C.D. et al.: Effect of atorvastatin on the pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel in healthy subjects. Pharmacotherapy 2008, 28: 1483-1494.
19. Stanek E.J., Aubert R.E., Flockhart D.A. et al.: A national study of the effect of individual proton pump inhibitors on cardiovascular outcomes in patients treated with clopidogrel following coronary stenting: the Clopidogrel Medco Outcomes Study. Paper presented at: SCAI 32nd Annual Scientific Sessions. Las Vegas, NV, 2009.
20. Wiviott S.D., Trenk D., Frelinger A.L. et al.: Prasugrel compared with high loading- and maintenance-dose clopidogrel in patients with planned percutaneous coronary intervention: the PRasugrel IN comparison to Clopidogrel for Inhibition of PLatelet activation and aggrEgation–Thrombolysis In Myocardial Infarction 44 trial. Circulation 2007, 116: 2923-2932.
21. Antman E.M., Wiviott S.D., Murphy S.A. et al.: Early and late benefits of prasugrel in patients with acute coronary syndromes undergoing percutaneous coronary intervention: a TRITON-TIMI 38 (TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel-Thrombolysis In Myocardial Infarction) analysis. J. Am. Coll. Cardiol. 2008, 51: 2028-33.
22. Muller I., Besta F., Schulz C. et al.: Prevalence of clopidogrel non-responders among patients with stable angina pectoris scheduled for elective coronary stent placement. Thromb. Haemost. 2003, 89: 783-787.
23. Matetzky S., Shenkman B., Guetta V. et al.: Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. Circulation 2004, 109: 3171-3175.
24. Simon T., Verstuyft C., Mary-Krause M. et al.: Genetic determinants of response to clopidogrel and cardiovascular events. N. Engl. J. Med. 2009, 360: 363-375.
25. Genotype Guided Comparison of Clopidogrel and Prasugrel Outcomes Study (GeCCO). Clinical Trials.gov [online: http://clinicaltrials.gov/ct2/ show/NCT00995514]. [Updated October 14, 2009. Accessed February 1, 2010].
26. Testing Platelet Reactivity In Patients Undergoing Elective Stent Placement on Clopidogrel to Guide Alternative Therapy With Prasugrel (TRIGGER-PCI). Clinical Trials.gov [online: http://clinicaltrials.gov/ct2/ show/NCT00910299]. [Updated January 27, 2010. Accessed February 1, 2010].
27. A Comparison of Prasugrel and Clopidogrel in Acute Coronary Syndrome Subjects (TRILOGY ACS). Clinical Trials.gov [online: http://clinicaltrials.gov/ct2/show/NCT00699998. [Updated January 15, 2010. Accessed February 1, 2010].
28. A Comparison of Prasugrel at PCI or Time of Diagnosis of Non-ST Elevation Myocardial Infarction (ACCOAST). Clinical Trials.gov [online: http://clinicaltrials.gov/ct2/show/NCT01015287]. [Updated January 15, 2010. Accessed February 1, 2010].
29. Third Optimizing Anti-Platelet Therapy in Diabetes MellitUS (OPTIMUS-3). Clinical Trials.gov [online: http://clinicaltrials.gov/ct2/show/NCT00642174]. [Updated July 13, 2009. Accessed February 1, 2010].
30. Angiolillo D.J., Badimon J., Saucedo J.F. et al.: Comparison of Prasugel With Clopidogrel on Platelet Function in Coronary Artery Disease Patients With Type 2 Diabetes Mellitus – Third Optimizing Anti-Platelet Therapy in Diabetes MellitUS (OPTIMUS-3). Circulation 2009, 120: 1027.
31. The Dual Antiplatelet Therapy Study (DAPT Study). Clinical Trials.gov [online: http://clinicaltrials.gov/ct2/show/NCT00977938].[Updated February 4, 2010. Accessed February 5, 2010].
32. Wiviott S.D., Antman E.M., Winters K.J. et al.: Randomized comparison of prasugrel (CS-747, LY640315), a novel thienopyridine P2Y12 antagonist, with clopidogrel in percutaneous coronary intervention: results of the Joint Utilization of Medications to Block Platelets Optimally (JUMBO)-TIMI 26 trial. Circulation. 2005, 111: 3366-3373.
33. O'Donoghue M., Antman E.M., Braunwald E. et al.: The efficacy and safety of prasugrel with and without a glycoprotein IIb/IIIa inhibitor in patients with acute coronary syndromes undergoing percutaneous intervention: a TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis In Myocardial Infarction 38) analysis. J. Am. Coll. Cardiol. 2009 Aug 18, 54(8): 678-85.
34. CAPRIE Steering Committee. A randomized, blinded trial of clopidogrel versus aspirin in patients at risk of ischemic events (CAPRIE). Lancet. 1996, 348: 1329-1339.
35. Unger E.F.: Weighing Benefits and Risks – The FDA’s Review of Prasugrel. N. Engl. J. Med. 2009, 361(10): 942-945.
36. National Institute for Health and Clinical Excellence Final appraisal determination – Prasugrel for the treatment of acute coronary syndromes with percutaneous coronary intervention. Issue date: October 2009. [online: http://www.nice.org.uk/TA182].
37. Focused Updates: ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction and ACC/AHA/SCAI Guidelines on Percutaneous Coronary Intervention. J. Am. Coll. Cardiol. 2009, 54: 2205-2241.
2. Clarke T.A., Waskell L.A.: The metabolism of clopidogrel is catalysed by human cytochrome P450 3A and is inhibited by Atorvastatin. Drug Metabolism Disp. 2002, 31: 1288-1295.
3. Serebruany V.L., Steinhubl S.R., Berger P.B. et al.: Variability in platelet responsiveness to clopidogrel among 544 individuals. J. Am. Coll. Cardiol. 2005, 45(2): 246-251.
4. Jaapjan D., Snoep J.D., Hovens M.M.C., Eikelboom J.W.: Clopidogrel nonresponsiveness in patients undergoing percutaneous coronary intervention with stenting: A systematic review and meta-analysis. Am. Heart J. 2007, 154: 221-231.
5. Lev E.I., Patel R.T., Maresh K.J.: Aspirin and clopidogrel drug response in patients undergoing Percutaneous Coronary Intervention. The role of dual drug resistance. J. Am. Coll. Cardiol. 2006, 47: 27-33.
6. Gori A.M., Marcucci R., Migliorini A.: Incidence and clinical impact of dual nonresponsiveness to aspirin and clopidogrel in patients with drug-eluting stents. J. Am. Coll. Cardiol. 2008, 52: 734-739.
7. Wenaweser P., Dörffler-Melly J., Imboden K. et al.: Stent thrombosis is associated with an impaired response to antiplatelet therapy. J Am Coll Cardiol. 2005, 45: 1748-1752.
8. Farid N.A., Smith R.L., Gillespie T.A. et al.: The disposition of prasugrel, a novel thienopyridine, in humans. Drug Metab Dispos. 2007, 35(7): 1096-104.
9. Niitsu Y., Jakubowski J.A., Sugidachi A. et al.: Pharmacology of CS-747 (prasugrel, LY640315), a novel, potent antiplatelet agent with in vivo P2Y12 receptor antagonist activity. Semin. Thromb. Hemost. 2005, 31: 184-194.
10. Payne C.D., Li Y.G., Small D.S. et al.: Increased active metabolite formation explains the greater platelet inhibition with prasugrel compared to high-dose clopidogrel. J. Cardiovasc. Pharmacol. 2007, 50: 555-562.
11. Wallentin L., Varenhorst C., James S. et al.: Prasugrel achieves greater and faster P2Y12 receptor-mediated platelet inhibition than clopidogrel due to more efficient generation of its active metabolite in aspirin treated patients with coronary artery disease. Eur. Heart J. 2008, 29: 21-30.
12. Rehmel J.L., Eckstein J.A., Farid N.A. et al.: Interactions of two major metabolites of prasugrel, a thienopyridine antiplatelet agent with the cytochromes P450. Drug Metab. Dispos. 2006, 34: 600-607.
13. Brandt J.T., Payne C.D., Wiviott S.D. et al.: A comparison of prasugrel and clopidogrel loading doses on platelet function: Magnitude of platelet inhibition is related to active metabolite formation. Am. Heart J. 2007, 153: 9-16.
14. Brandt J.T., Close S.L., Iturria S.J. et al.: Common polymorphisms of CYP2C19 and CYP2C9 affect the pharmacokinetic and pharmacodynamic response to clopidogrel but not prasugrel. J. Thromb. Haemost. 2007, 5: 2429-2436.
15. Mega J.L., Close S.L., Wiviott S.D. et al.: Cytochrome P-450 polymorphisms and response to clopidogrel. N. Engl. J. Med. 2009, 360: 354-362.
16. Juurlink D.N., Gomes T., Ko D.T. et al.: A population based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ. 2009, 180: 713-718.
17. Lau W.C., Waskell L.A., Watkins P.B. et al.: Atorvastatin reduces the ability of clopidogrel to inhibit platelet aggregation: a new drug-drug interaction. Circulation 2003, 107: 32-37.
18. Farid N.A., Small D.S., Payne C.D. et al.: Effect of atorvastatin on the pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel in healthy subjects. Pharmacotherapy 2008, 28: 1483-1494.
19. Stanek E.J., Aubert R.E., Flockhart D.A. et al.: A national study of the effect of individual proton pump inhibitors on cardiovascular outcomes in patients treated with clopidogrel following coronary stenting: the Clopidogrel Medco Outcomes Study. Paper presented at: SCAI 32nd Annual Scientific Sessions. Las Vegas, NV, 2009.
20. Wiviott S.D., Trenk D., Frelinger A.L. et al.: Prasugrel compared with high loading- and maintenance-dose clopidogrel in patients with planned percutaneous coronary intervention: the PRasugrel IN comparison to Clopidogrel for Inhibition of PLatelet activation and aggrEgation–Thrombolysis In Myocardial Infarction 44 trial. Circulation 2007, 116: 2923-2932.
21. Antman E.M., Wiviott S.D., Murphy S.A. et al.: Early and late benefits of prasugrel in patients with acute coronary syndromes undergoing percutaneous coronary intervention: a TRITON-TIMI 38 (TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel-Thrombolysis In Myocardial Infarction) analysis. J. Am. Coll. Cardiol. 2008, 51: 2028-33.
22. Muller I., Besta F., Schulz C. et al.: Prevalence of clopidogrel non-responders among patients with stable angina pectoris scheduled for elective coronary stent placement. Thromb. Haemost. 2003, 89: 783-787.
23. Matetzky S., Shenkman B., Guetta V. et al.: Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. Circulation 2004, 109: 3171-3175.
24. Simon T., Verstuyft C., Mary-Krause M. et al.: Genetic determinants of response to clopidogrel and cardiovascular events. N. Engl. J. Med. 2009, 360: 363-375.
25. Genotype Guided Comparison of Clopidogrel and Prasugrel Outcomes Study (GeCCO). Clinical Trials.gov [online: http://clinicaltrials.gov/ct2/ show/NCT00995514]. [Updated October 14, 2009. Accessed February 1, 2010].
26. Testing Platelet Reactivity In Patients Undergoing Elective Stent Placement on Clopidogrel to Guide Alternative Therapy With Prasugrel (TRIGGER-PCI). Clinical Trials.gov [online: http://clinicaltrials.gov/ct2/ show/NCT00910299]. [Updated January 27, 2010. Accessed February 1, 2010].
27. A Comparison of Prasugrel and Clopidogrel in Acute Coronary Syndrome Subjects (TRILOGY ACS). Clinical Trials.gov [online: http://clinicaltrials.gov/ct2/show/NCT00699998. [Updated January 15, 2010. Accessed February 1, 2010].
28. A Comparison of Prasugrel at PCI or Time of Diagnosis of Non-ST Elevation Myocardial Infarction (ACCOAST). Clinical Trials.gov [online: http://clinicaltrials.gov/ct2/show/NCT01015287]. [Updated January 15, 2010. Accessed February 1, 2010].
29. Third Optimizing Anti-Platelet Therapy in Diabetes MellitUS (OPTIMUS-3). Clinical Trials.gov [online: http://clinicaltrials.gov/ct2/show/NCT00642174]. [Updated July 13, 2009. Accessed February 1, 2010].
30. Angiolillo D.J., Badimon J., Saucedo J.F. et al.: Comparison of Prasugel With Clopidogrel on Platelet Function in Coronary Artery Disease Patients With Type 2 Diabetes Mellitus – Third Optimizing Anti-Platelet Therapy in Diabetes MellitUS (OPTIMUS-3). Circulation 2009, 120: 1027.
31. The Dual Antiplatelet Therapy Study (DAPT Study). Clinical Trials.gov [online: http://clinicaltrials.gov/ct2/show/NCT00977938].[Updated February 4, 2010. Accessed February 5, 2010].
32. Wiviott S.D., Antman E.M., Winters K.J. et al.: Randomized comparison of prasugrel (CS-747, LY640315), a novel thienopyridine P2Y12 antagonist, with clopidogrel in percutaneous coronary intervention: results of the Joint Utilization of Medications to Block Platelets Optimally (JUMBO)-TIMI 26 trial. Circulation. 2005, 111: 3366-3373.
33. O'Donoghue M., Antman E.M., Braunwald E. et al.: The efficacy and safety of prasugrel with and without a glycoprotein IIb/IIIa inhibitor in patients with acute coronary syndromes undergoing percutaneous intervention: a TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis In Myocardial Infarction 38) analysis. J. Am. Coll. Cardiol. 2009 Aug 18, 54(8): 678-85.
34. CAPRIE Steering Committee. A randomized, blinded trial of clopidogrel versus aspirin in patients at risk of ischemic events (CAPRIE). Lancet. 1996, 348: 1329-1339.
35. Unger E.F.: Weighing Benefits and Risks – The FDA’s Review of Prasugrel. N. Engl. J. Med. 2009, 361(10): 942-945.
36. National Institute for Health and Clinical Excellence Final appraisal determination – Prasugrel for the treatment of acute coronary syndromes with percutaneous coronary intervention. Issue date: October 2009. [online: http://www.nice.org.uk/TA182].
37. Focused Updates: ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction and ACC/AHA/SCAI Guidelines on Percutaneous Coronary Intervention. J. Am. Coll. Cardiol. 2009, 54: 2205-2241.