Circulation. 2005;111:3366-3373
Published online before print June 20, 2005,
doi: 10.1161/CIRCULATIONAHA.104.502815
(Circulation. 2005;111:3366-3373.)
© 2005 American Heart Association, Inc.
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
Stephen D. Wiviott, MD;
Elliott M. Antman, MD;
Kenneth J. Winters, MD;
Govinda Weerakkody, PhD;
Sabina A. Murphy, MS;
Bruce D. Behounek, MD;
Robert J. Carney, MD;
Charles Lazzam, MD;
Raymond G. McKay, MD;
Carolyn H. McCabe, BS;
Eugene Braunwald, MD, for the JUMBO–TIMI 26 Investigators
From the TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital, Department of Medicine, Harvard Medical School, Boston, Mass (S.D.W., E.M.A., S.A.M., C.M.C., E.B.); Eli Lilly and Co, Indianapolis, Ind (K.J.W., G.W.); Sankyo Co, Ltd, Tokyo, Japan (B.D.B.); Mother Francis Hospital, Tyler, Tex (R.J.C.); Trillium Health Center, Mississauga, Ontario, Canada (C.L.); and Hartford Hospital, Hartford, Conn (R.G.M.).
Correspondence to Stephen D. Wiviott, MD, TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115. E-mail swiviott{at}partners.org
Received August 26, 2004; revision received January 10, 2005; accepted March 8, 2005.
Background— Despite the current standard antiplatelet regimen of aspirin and clopidogrel (with or without glycoprotein IIb/IIIa inhibitors) in percutaneous coronary intervention patients, periprocedural and postprocedural ischemic events continue to occur. Prasugrel (CS-747, LY640315), a novel potent thienopyridine P2Y12 receptor antagonist, has the potential to achieve higher levels of inhibition of ADP-induced platelet aggregation than currently approved doses of clopidogrel.
Methods and Results— Joint Utilization of Medications to Block Platelets Optimally–Thrombolysis In Myocardial Infarction 26 (JUMBO-TIMI 26) was a phase 2, randomized, dose-ranging, double-blind safety trial of prasugrel versus clopidogrel in 904 patients undergoing elective or urgent percutaneous coronary intervention. Patients were randomized to either standard dosing with clopidogrel or 1 of 3 prasugrel regimens. Subjects were monitored for 30 days for bleeding and clinical events. The primary end point of the trial was clinically significant (TIMI major plus minor) non–CABG-related bleeding events in prasugrel- versus clopidogrel-treated patients. Hemorrhagic complications were infrequent, with no significant difference between patients treated with prasugrel or clopidogrel in the rate of significant bleeding (1.7% versus 1.2%; hazard ratio, 1.42; 95% CI, 0.40, 5.08). In prasugrel-treated patients, there were numerically lower incidences of the primary efficacy composite end point (30-day major adverse cardiac events) and of the secondary end points myocardial infarction, recurrent ischemia, and clinical target vessel thrombosis.
Conclusions— In this phase 2 study, which was designed to assess safety when administered at the time of percutaneous coronary intervention, prasugrel and clopidogrel both resulted in low rates of bleeding. The results of this trial serve as a foundation for the large phase 3 clinical trial designed to assess both efficacy and safety.
Key Words: coronary disease • drugs • hemorrhage • platelets • stents
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95(10):
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[Full Text]
[PDF]
|
|
|
|
|
|
|
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[Abstract]
[PDF]
|
|
|
|
|
|
|
S. S. Smyth, D. S. Woulfe, J. I. Weitz, C. Gachet, P. B. Conley, S. G. Goodman, M. T. Roe, A. Kuliopulos, D. J. Moliterno, P. A. French, et al.
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29(4):
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[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]
|
|
|
|
|
|
|
M. J. Price
New antiplatelet therapies in development
Am. J. Health Syst. Pharm.,
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65(13_Supplement_5):
S11 - S15.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. B. Riley, M. J. Tafreshi, and S. L. Haber
Prasugrel: A novel antiplatelet agent
Am. J. Health Syst. Pharm.,
June 1, 2008;
65(11):
1019 - 1028.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. I. Weitz, J. Hirsh, and M. M. Samama
New Antithrombotic Drugs: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)
Chest,
June 1, 2008;
133(6_suppl):
234S - 256S.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Harrington, R. C. Becker, C. P. Cannon, D. Gutterman, A. M. Lincoff, J. J. Popma, G. Steg, G. H. Guyatt, and S. G. Goodman
Antithrombotic Therapy for Non-ST-Segment Elevation Acute Coronary Syndromes: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)
Chest,
June 1, 2008;
133(6_suppl):
670S - 707S.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-P. Bassand
Unmet needs in antiplatelet therapy
Eur. Heart J. Suppl.,
May 1, 2008;
10(suppl_D):
D3 - D11.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. F. Storey
New developments in antiplatelet therapy
Eur. Heart J. Suppl.,
May 1, 2008;
10(suppl_D):
D30 - D37.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.J.J. van Giezen
Optimizing platelet inhibition
Eur. Heart J. Suppl.,
May 1, 2008;
10(suppl_D):
D23 - D29.
[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]
|
|
|
|
|
|
|
A. D. Michelson
P2Y12 Antagonism: Promises and Challenges
Arterioscler. Thromb. Vasc. Biol.,
March 1, 2008;
28(3):
s33 - s38.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Wallentin, C. Varenhorst, S. James, D. Erlinge, O. O Braun, J. A. Jakubowski, A. Sugidachi, K. J. Winters, and A. Siegbahn
Prasugrel achieves greater and faster P2Y12receptor-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.,
January 1, 2008;
29(1):
21 - 30.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. D. Wiviott, E. Braunwald, C. H. McCabe, G. Montalescot, W. Ruzyllo, S. Gottlieb, F.-J. Neumann, D. Ardissino, S. De Servi, S. A. Murphy, et al.
Prasugrel versus Clopidogrel in Patients with Acute Coronary Syndromes
N. Engl. J. Med.,
November 15, 2007;
357(20):
2001 - 2015.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. J. Weerakkody, J. A. Jakubowski, J. T. Brandt, C. D. Payne, H. Naganuma, and K. J. Winters
Greater Inhibition of Platelet Aggregation and Reduced Response Variability With Prasugrel Versus Clopidogrel: An Integrated Analysis
Journal of Cardiovascular Pharmacology and Therapeutics,
September 1, 2007;
12(3):
205 - 212.
[Abstract]
[PDF]
|
|
|
|
|
|
|
S. M. Donahoe, G. C. Stewart, C. H. McCabe, S. Mohanavelu, S. A. Murphy, C. P. Cannon, and E. M. Antman
Diabetes and Mortality Following Acute Coronary Syndromes
JAMA,
August 15, 2007;
298(7):
765 - 775.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Bode and M. Zehender
The use of antiplatelet agents following percutaneous coronary intervention: focus on late stent thrombosis
Eur. Heart J. Suppl.,
August 1, 2007;
9(suppl_D):
D10 - D19.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Husted
New developments in oral antiplatelet therapy
Eur. Heart J. Suppl.,
August 1, 2007;
9(suppl_D):
D20 - D27.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. R. Holmes Jr, D. J. Kereiakes, W. K. Laskey, A. Colombo, S. G. Ellis, T. D. Henry, J. J. Popma, P. W.J.C. Serruys, T. Kimura, D. O. Williams, et al.
Thrombosis and Drug-Eluting Stents: An Objective Appraisal
J. Am. Coll. Cardiol.,
July 10, 2007;
50(2):
109 - 118.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Buonamici, R. Marcucci, A. Migliorini, G. F. Gensini, A. Santini, R. Paniccia, G. Moschi, A. M. Gori, R. Abbate, and D. Antoniucci
Impact of Platelet Reactivity After Clopidogrel Administration on Drug-Eluting Stent Thrombosis
J. Am. Coll. Cardiol.,
June 19, 2007;
49(24):
2312 - 2317.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. A. Meadows and D. L. Bhatt
Clinical Aspects of Platelet Inhibitors and Thrombus Formation
Circ. Res.,
May 11, 2007;
100(9):
1261 - 1275.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. O. Maree and D. J. Fitzgerald
Variable Platelet Response to Aspirin and Clopidogrel in Atherothrombotic Disease
Circulation,
April 24, 2007;
115(16):
2196 - 2207.
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. J. Angiolillo, A. Fernandez-Ortiz, E. Bernardo, F. Alfonso, C. Macaya, T. A. Bass, and M. A. Costa
Variability in Individual Responsiveness to Clopidogrel: Clinical Implications, Management, and Future Perspectives
J. Am. Coll. Cardiol.,
April 10, 2007;
49(14):
1505 - 1516.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. O'Donoghue and S. D. Wiviott
Clopidogrel Response Variability and Future Therapies: Clopidogrel: Does One Size Fit All?
Circulation,
November 28, 2006;
114(22):
e600 - e606.
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Hochholzer, D. Trenk, H.-P. Bestehorn, B. Fischer, C. M. Valina, M. Ferenc, M. Gick, A. Caputo, H. J. Buttner, and F.-J. Neumann
Impact of the Degree of Peri-Interventional Platelet Inhibition After Loading With Clopidogrel on Early Clinical Outcome of Elective Coronary Stent Placement
J. Am. Coll. Cardiol.,
November 7, 2006;
48(9):
1742 - 1750.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Ibanez, G. Vilahur, and J. J. Badimon
Pharmacology of thienopyridines: rationale for dual pathway inhibition
Eur. Heart J. Suppl.,
October 1, 2006;
8(suppl_G):
G3 - G9.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Hamdalla and S. R. Steinhubl
Clinical efficacy of clopidogrel across the whole spectrum of indications: percutaneous coronary intervention
Eur. Heart J. Suppl.,
October 1, 2006;
8(suppl_G):
G20 - G24.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. D. Michelson, A. L. Frelinger, and M. I. Furman
Resistance to antiplatelet drugs
Eur. Heart J. Suppl.,
October 1, 2006;
8(suppl_G):
G53 - G58.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-S. Hulot, A. Bura, E. Villard, M. Azizi, V. Remones, C. Goyenvalle, M. Aiach, P. Lechat, and P. Gaussem
Cytochrome P450 2C19 loss-of-function polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects
Blood,
October 1, 2006;
108(7):
2244 - 2247.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Jernberg and L. Wallentin
Prasugrel, clopidogrel, and combining Swedish apples with American oranges: reply
Eur. Heart J.,
August 1, 2006;
27(15):
1887 - 1888.
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. L. Serebruany
Prasugrel, clopidogrel, and combining Swedish apples with American oranges
Eur. Heart J.,
August 1, 2006;
27(15):
1886 - 1887.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. L. Frelinger III, M. I. Furman, M. D. Linden, Y. Li, M. L. Fox, M. R. Barnard, and A. D. Michelson
Residual Arachidonic Acid-Induced Platelet Activation via an Adenosine Diphosphate-Dependent but Cyclooxygenase-1- and Cyclooxygenase-2-Independent Pathway: A 700-Patient Study of Aspirin Resistance
Circulation,
June 27, 2006;
113(25):
2888 - 2896.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V L Serebruany, M G Midei, H Meilman, A I Malinin, and D R Lowry
Platelet inhibition with prasugrel (CS-747) compared with clopidogrel in patients undergoing coronary stenting: the subset from the JUMBO study.
Postgrad. Med. J.,
June 1, 2006;
82(968):
404 - 410.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Jernberg, C. D. Payne, K. J. Winters, C. Darstein, J. T. Brandt, J. A. Jakubowski, H. Naganuma, A. Siegbahn, and L. Wallentin
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.,
May 2, 2006;
27(10):
1166 - 1173.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Cattaneo
P2Y12 receptor antagonists: a rapidly expanding group of antiplatelet agents
Eur. Heart J.,
May 1, 2006;
27(9):
1010 - 1012.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. R. Dixon, C. L. Grines, and W. W. O'Neill
The Year in Interventional Cardiology
J. Am. Coll. Cardiol.,
April 18, 2006;
47(8):
1689 - 1706.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Kastrati, J. Mehilli, F.-J. Neumann, F. Dotzer, J. ten Berg, H. Bollwein, I. Graf, M. Ibrahim, J. Pache, M. Seyfarth, et al.
Abciximab in Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention After Clopidogrel Pretreatment: The ISAR-REACT 2 Randomized Trial
JAMA,
April 5, 2006;
295(13):
1531 - 1538.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. H. Wang, D. L. Bhatt, and E. J. Topol
Aspirin and clopidogrel resistance: an emerging clinical entity
Eur. Heart J.,
March 2, 2006;
27(6):
647 - 654.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. P. Giugliano and E. Braunwald
The Year in Non--ST-Segment Elevation Acute Coronary Syndromes
J. Am. Coll. Cardiol.,
September 6, 2005;
46(5):
906 - 919.
[Full Text]
[PDF]
|
|
|
