Published online before print December 3, 2007, doi: 10.1161/CIRCULATIONAHA.107.740324
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2007;116:2923-2932.)
© 2007 American Heart Association, Inc.
Coronary Heart Disease |
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
From the TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital, Boston, Mass (S.D.W., S.A.M., C.H.M., E.M.A., E.B.); Cardiovascular Division, Massachusetts General Hospital, Boston (M.O.); Herz-Zentrum Bad Krozingen, Bad Krozingen, Germany (D.T., F.-J.N.); Center for Platelet Function Studies, Departments of Pediatrics, Medicine and Pathology, University of Massachusetts Medical School, Worcester (A.L.F., A.D.M.); University of Florida, College of Medicine, Jacksonville (D.J.A.); The Heart Institute, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv, Israel (H.H.); Institut de Cardiologie and INSERM Unit 856, Petie-Salpetriere University Hospital, Paris, France (G.M.); Lilly Research Laboratories, Eli Lilly and Co, Indianapolis, Ind (D.L.M., J.A.J.); and Nottingham Clinical Research Ltd, Nottingham, UK (R.C.).
Correspondence to Stephen D. Wiviott, MD, Brigham and Women’s Hospital, Cardiovascular Division, 75 Francis St, Boston, MA 02115. E-mail swiviott{at}partners.org
Received September 14, 2007; accepted October 17, 2007.
Background— The increasing use of higher-than-approved doses of clopidogrel in clinical practice is based in part on the desire for greater levels of inhibition of platelet aggregation (IPA). Prasugrel is a new thienopyridine that is more potent than standard-dose clopidogrel in healthy subjects and patients with stable coronary artery disease. The relative antiplatelet effects of prasugrel versus high-dose clopidogrel in percutaneous coronary intervention patients are unknown.
Methods and Results— Prasugrel in Comparison to Clopidogrel for Inhibition of Platelet Activation and Aggregation–Thrombolysis in Myocardial Infarction 44 (PRINCIPLE-TIMI 44) was a randomized, double-blind, 2-phase crossover study of prasugrel compared with high-dose clopidogrel in patients undergoing cardiac catheterization for planned percutaneous coronary intervention. The primary end point of the loading-dose phase (prasugrel 60 mg versus clopidogrel 600 mg) was IPA with 20 µmol/L ADP at 6 hours. Patients with percutaneous coronary intervention entered the maintenance-dose phase, a 28-day crossover comparison of prasugrel 10 mg/d versus clopidogrel 150 mg/d with a primary end point of IPA after 14 days of either drug. In this study, 201 subjects were randomized. IPA at 6 hours was significantly higher in subjects receiving prasugrel (mean±SD, 74.8±13.0%) compared with clopidogrel (31.8±21.1%; P<0.0001). During the maintenance-dose phase, IPA with 20 µmol/L ADP was higher in subjects receiving prasugrel (61.3±17.8%) compared with clopidogrel (46.1±21.3%; P<0.0001). Results were consistent across all key secondary end points; significant differences emerged by 30 minutes and persisted across all time points.
Conclusions— Among patients undergoing cardiac catheterization with planned percutaneous coronary intervention, loading with 60 mg prasugrel resulted in greater platelet inhibition than a 600-mg clopidogrel loading dose. Maintenance therapy with prasugrel 10 mg/d resulted in a greater antiplatelet effect than 150 mg/d clopidogrel.
CLINICAL PERSPECTIVE
Related Article:
-
Issue Highlights
Circulation 2007 116: 2893.[Extract] [Full Text]
This article has been cited by other articles:
 |
|
 |
|
  D. R. Holmes Jr, D. J. Kereiakes, N. S. Kleiman, D. J. Moliterno, G. Patti, and C. L. Grines Combining Antiplatelet and Anticoagulant Therapies. J. Am. Coll. Cardiol., July 7, 2009; 54(2): 95 - 109. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Morrow, S. D. Wiviott, H. D. White, J. C. Nicolau, E. Bramucci, S. A. Murphy, M. P. Bonaca, C. T. Ruff, B. M. Scirica, C. H. McCabe, et al. Effect of the Novel Thienopyridine Prasugrel Compared With Clopidogrel on Spontaneous and Procedural Myocardial Infarction in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction 38: An Application of the Classification System From the Universal Definition of Myocardial Infarction Circulation, June 2, 2009; 119(21): 2758 - 2764. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Mega, S. L. Close, S. D. Wiviott, L. Shen, R. D. Hockett, J. T. Brandt, J. R. Walker, E. M. Antman, W. L. Macias, E. Braunwald, et al. Cytochrome P450 Genetic Polymorphisms and the Response to Prasugrel: Relationship to Pharmacokinetic, Pharmacodynamic, and Clinical Outcomes Circulation, May 19, 2009; 119(19): 2553 - 2560. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Tousoulis, A. Briasoulis, S. S Dhamrait, C. Antoniades, and C. Stefanadis Effective platelet inhibition by aspirin and clopidogrel: where are we now? Heart, May 1, 2009; 95(10): 850 - 858. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Veverka and J. M. Hammer Prasugrel: A New Thienopyridine Inhibitor Journal of Pharmacy Practice, April 1, 2009; 22(2): 158 - 165. [Abstract] [PDF]
|
|
|
|
 |
|
 M. S. SABATINE Novel antiplatelet strategies in acute coronary syndromes Cleveland Clinic Journal of Medicine, April 1, 2009; 76(Suppl_1): S8 - S15. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. H. Jeong, S.-W. Lee, B.-R. Choi, I.-S. Kim, M.-K. Seo, C. H. Kwak, J.-Y. Hwang, and S.-W. Park Randomized Comparison of Adjunctive Cilostazol Versus High Maintenance Dose Clopidogrel in Patients With High Post-Treatment Platelet Reactivity Results of the ACCEL-RESISTANCE (Adjunctive Cilostazol Versus High Maintenance Dose Clopidogrel in Patients With Clopidogrel Resistance) Randomized Study. J. Am. Coll. Cardiol., March 31, 2009; 53(13): 1101 - 1109. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Scott, R. M Norwood, and D. Parra P2Y12 Inhibitors in Cardiovascular Disease: Focus on Prasugrel Ann. Pharmacother., January 1, 2009; 43(1): 64 - 76. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Fuster and M. E. Farkouh Acute Coronary Syndromes and Diabetes Mellitus: A Winning Ticket for Prasugrel Circulation, October 14, 2008; 118(16): 1607 - 1608. [Full Text] [PDF]
|
|
|
|
|
|
S. D. Wiviott, E. Braunwald, D. J. Angiolillo, S. Meisel, A. J. Dalby, F. W.A. Verheugt, S. G. Goodman, R. Corbalan, D. A. Purdy, S. A. Murphy, et al. Greater Clinical Benefit of More Intensive Oral Antiplatelet Therapy With Prasugrel in Patients With Diabetes Mellitus in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction 38 Circulation, October 14, 2008; 118(16): 1626 - 1636. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. O. Williams and J. D. Abbott What to Do With Patients Receiving Long-Term Clopidogrel: Reload or Relax? Circulation, September 16, 2008; 118(12): 1219 - 1222. [Full Text] [PDF]
|
|
|
|
|
|
J.-P. Collet, J. Silvain, A. Landivier, M.-L. Tanguy, G. Cayla, A. Bellemain, N. Vignolles, S. Gallier, F. Beygui, A. Pena, et al. Dose Effect of Clopidogrel Reloading in Patients Already on 75-mg Maintenance Dose: The Reload With Clopidogrel Before Coronary Angioplasty in Subjects Treated Long Term With Dual Antiplatelet Therapy (RELOAD) Study Circulation, September 16, 2008; 118(12): 1225 - 1233. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Schiele, N. Meneveau, and J.-P. Bassand Routine pre-treatment with clopidogrel before diagnostic coronary angiography: the question is right, but what about the answer? Eur. Heart J., June 2, 2008; 29(12): 1475 - 1477. [Full Text] [PDF]
|
|
|
|
|
|
E. M. Antman, S. D. Wiviott, S. A. Murphy, J. Voitk, Y. Hasin, P. Widimsky, H. Chandna, W. Macias, C. H. McCabe, and E. Braunwald 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., May 27, 2008; 51(21): 2028 - 2033. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Kereiakes and P. A. Gurbel Peri-Procedural Platelet Function and Platelet Inhibition in Percutaneous Coronary Intervention J. Am. Coll. Cardiol. Intv., April 1, 2008; 1(2): 111 - 121. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Serebruany, V. Pasceri, G. Patti, G. Di Sciascio, F. von Lewinski, J. Riggert, W. Paulus, S. D. Wiviott, E. Braunwald, E. M. Antman, et al. Prasugrel versus Clopidogrel N. Engl. J. Med., March 20, 2008; 358(12): 1298 - 1301. [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. Michelson P2Y12 Antagonism: Promises and Challenges Arterioscler. Thromb. Vasc. Biol., March 1, 2008; 28(3): s33 - s38. [Abstract] [Full Text] [PDF]
|
|