CLINICAL STUDY
Meta-analysis of randomized and registry comparisons of ticlopidine with clopidogrel after stenting
Deepak L. Bhatt, MD*,
Michel E. Bertrand, MD, FACC ,
Peter B. Berger, MD, FACC ,
Philippe L. L’Allier, MD ,
Issam Moussa, MD, FACC||,
Jeffrey W. Moses, MD, FACC||,
George Dangas, MD, PhD, FACC||,
Megumi Taniuchi, MD, FACC¶,
John M. Lasala, MD, FACC¶,
David R. Holmes, MD, FACC,
Stephen G. Ellis, MD, FACC* and
Eric J. Topol, MD, FACC*,*
* Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USA
Hopital Cardiologique, Lille, France
Mayo Clinic, Rochester, Minnesota, USA
Montreal Heart Institute, Montreal, Canada
|| Lenox Hill Heart and Vascular Institute, New York, New York, USA
¶ Washington University, St. Louis, Missouri, USA
Manuscript received May 8, 2001;
revised manuscript received August 21, 2001,
accepted October 11, 2001.
* Reprint requests and correspondence: Dr. Eric J. Topol, Department of Cardiovascular Medicine, F25, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.
topole{at}ccf.org
OBJECTIVES: We sought to determine whether clopidogrel is at least as efficacious as ticlopidine.
BACKGROUND: Several trials have supported the enhanced safety and tolerability of clopidogrel compared with ticlopidine after coronary stent deployment. However, none of these individual trials were powered to detect possible differences in the efficacy for reducing ischemic end points.
METHODS: Published data from trials and registries that compared clopidogrel with ticlopidine in patients receiving coronary stents were pooled, and a formal meta-analysis was performed. The rate of 30-day major adverse cardiac events (MACE), as defined in each trial, was used as the primary end point.
RESULTS: There were a total of 13,955 patients. The pooled rate of major adverse cardiac events was 2.10% in the clopidogrel group and 4.04% in the ticlopidine group. After adjustment for heterogeneity in the trials, the odds ratio (OR) of having an ischemic event with clopidogrel, as compared with ticlopidine, was 0.72 (95% confidence interval [CI] 0.59 to 0.89, p = 0.002). Mortality was also lower in the clopidogrel group compared with the ticlopidine group—0.48% versus 1.09% (OR 0.55, 95% CI 0.37 to 0.82; p = 0.003).
CONCLUSIONS: Based on all available evidence from randomized clinical trials or registries, clopidogrel, in addition to better tolerability and fewer side effects, is at least as efficacious as ticlopidine in reducing MACE. This finding may be due to the more rapid onset of an antiplatelet effect seen with the loading dose of clopidogrel, which was used in most of these studies, or to better patient compliance with clopidogrel therapy. Therefore, clopidogrel plus aspirin should replace ticlopidine plus aspirin as the standard antiplatelet regimen after stent deployment.
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Abbreviations and Acronyms
| | ADP | | adenosine diphosphate | | CI | | confidence interval | | CLASSICS | | CLopidogrel ASpirin Stent International Cooperative Study | | MACE | | major adverse cardiac events | | MI | | myocardial infarction | | OR | | odds ratio | | SAST | | subacute stent thrombosis | | TOPPS | | Ticlid Or Plavix Post-Stent | | TTP | | thrombotic thrombocytopenic purpura | | TVR | | target vessel revascularization |
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133(6_suppl):
199S - 233S.
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|
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|
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|
|
|
|
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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9(suppl_D):
D10 - D19.
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[PDF]
|
|
|
|
|
|
|
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49(24):
2312 - 2317.
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|
|
|
|
|
|
|
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100(9):
1261 - 1275.
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[PDF]
|
|
|
|
|
|
|
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J Am Dent Assoc,
May 1, 2007;
138(5):
652 - 655.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. M. Howard-Alpe, J. de Bono, L. Hudsmith, W. P. Orr, P. Foex, and J. W. Sear
Coronary artery stents and non-cardiac surgery
Br. J. Anaesth.,
May 1, 2007;
98(5):
560 - 574.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Eshaghian, S. Kaul, S. Amin, P. K. Shah, and G. A. Diamond
Role of Clopidogrel in Managing Atherothrombotic Cardiovascular Disease
Ann Intern Med,
March 20, 2007;
146(6):
434 - 441.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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Prevention of Premature Discontinuation of Dual Antiplatelet Therapy in Patients With Coronary Artery Stents: A Science Advisory From the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, With Representation From the American College of Physicians
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February 13, 2007;
49(6):
734 - 739.
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[Full Text]
[PDF]
|
|
|
|
|
|
|
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February 13, 2007;
115(6):
813 - 818.
[Abstract]
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[PDF]
|
|
|
|
|
|
|
D. Dudek, A. Dziewierz, B. Chyrchel, L. Polonski, J. Legutko, and J. S. Dubiel
Antiplatelet treatment in non-ST-segment elevation acute coronary syndrome patients undergoing percutaneous coronary intervention (ISAR-REACT 2 insight)
Eur. Heart J. Suppl.,
February 1, 2007;
9(suppl_A):
A25 - A31.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Geisler, H. Langer, M. Wydymus, K. Gohring, C. Zurn, B. Bigalke, K. Stellos, A. E. May, and M. Gawaz
Low response to clopidogrel is associated with cardiovascular outcome after coronary stent implantation
Eur. Heart J.,
October 2, 2006;
27(20):
2420 - 2425.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Onizuka, K. Kazekawa, S. Nagata, M. Tsutsumi, H. Aikawa, M. Tomokiyo, M. Iko, T. Kodama, K. Nii, S. Matsubara, et al.
The Significance of Incomplete Stent Apposition in Patients Undergoing Stenting of Internal Carotid Artery Stenosis
AJNR Am. J. Neuroradiol.,
August 1, 2006;
27(7):
1505 - 1507.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Chaturvedi and J. S. Yadav
The Role of Antiplatelet Therapy in Carotid Stenting for Ischemic Stroke Prevention
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June 1, 2006;
37(6):
1572 - 1577.
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[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Kohyama, K. Kazekawa, M. Iko, H. Aikawa, M. Tsutsumi, Y. Go, S. Nagata, T. Kodama, K. Nii, S. Matsubara, et al.
Spontaneous Improvement of Peristent Ulceration after Carotid Artery Stenting
AJNR Am. J. Neuroradiol.,
January 1, 2006;
27(1):
151 - 156.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. D. Wiviott, E. M. Antman, K. J. Winters, G. Weerakkody, S. A. Murphy, B. D. Behounek, R. J. Carney, C. Lazzam, R. G. McKay, C. H. McCabe, 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,
June 28, 2005;
111(25):
3366 - 3373.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Ajzenberg, P. Aubry, M.-G. Huisse, A. Cachier, W. El Amara, L. J. Feldman, D. Himbert, D. Baruch, M.-C. Guillin, and Ph. G. Steg
Enhanced Shear-Induced Platelet Aggregation in Patients Who Experience Subacute Stent Thrombosis: A Case-Control Study
J. Am. Coll. Cardiol.,
June 7, 2005;
45(11):
1753 - 1756.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R V Kelly and S Steinhubl
Changing roles of anticoagulant and antiplatelet treatment during percutaneous coronary intervention
Heart,
June 1, 2005;
91(suppl_3):
iii16 - iii19.
[Full Text]
[PDF]
|
|
|
|
|
|
|
H Suryapranata, G De Luca, A W J van 't Hof, J P Ottervanger, J C A Hoorntje, J-H E Dambrink, A T M Gosselink, F Zijlstra, and M-J de Boer
Is routine stenting for acute myocardial infarction superior to balloon angioplasty? A randomised comparison in a large cohort of unselected patients
Heart,
May 1, 2005;
91(5):
641 - 645.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Patti, G. Colonna, V. Pasceri, L. L. Pepe, A. Montinaro, and G. Di Sciascio
Randomized Trial of High Loading Dose of Clopidogrel for Reduction of Periprocedural Myocardial Infarction in Patients Undergoing Coronary Intervention: Results From the ARMYDA-2 (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) Study
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April 26, 2005;
111(16):
2099 - 2106.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. A. Nguyen, J. G. Diodati, and C. Pharand
Resistance to clopidogrel: A review of the evidence
J. Am. Coll. Cardiol.,
April 19, 2005;
45(8):
1157 - 1164.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Authors/Task Force Members, S. Silber, P. Albertsson, F. F. Aviles, P. G. Camici, A. Colombo, C. Hamm, E. Jorgensen, J. Marco, J.-E. Nordrehaug, et al.
Guidelines for Percutaneous Coronary Interventions: The Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology
Eur. Heart J.,
April 2, 2005;
26(8):
804 - 847.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. A. Bavry, D. J. Kumbhani, T. J. Helton, and D. L. Bhatt
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J. Am. Coll. Cardiol.,
March 15, 2005;
45(6):
941 - 946.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. J. Lansky, J. S. Hochman, P. A. Ward, G. S. Mintz, R. Fabunmi, P. B. Berger, G. New, C. L. Grines, C. G. Pietras, M. J. Kern, et al.
Percutaneous Coronary Intervention and Adjunctive Pharmacotherapy in Women: A Statement for Healthcare Professionals From the American Heart Association
Circulation,
February 22, 2005;
111(7):
940 - 953.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. A. Cowper, K. Udayakumar, M. H. Sketch Jr, and E. D. Peterson
Economic effects of prolonged clopidogrel therapy after percutaneous coronary intervention
J. Am. Coll. Cardiol.,
February 1, 2005;
45(3):
369 - 376.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. S. Wiggins and S. Spinler
Antiplatelet and Antithrombin Therapy for Early Management of Acute Coronary Syndromes
Journal of Pharmacy Practice,
October 1, 2004;
17(5):
347 - 369.
[Abstract]
[PDF]
|
|
|
|
|
|
|
C. Patrono, B. Coller, G. A. FitzGerald, J. Hirsh, and G. Roth
Platelet-Active Drugs: The Relationships Among Dose, Effectiveness, and Side Effects: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy
Chest,
September 1, 2004;
126(3_suppl):
234S - 264S.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. L. Stadius
Diminishing returns ...and too many choices ...the saga of pharmacologic therapy to reduce the complications of percutaneous coronary intervention
J. Am. Coll. Cardiol.,
July 7, 2004;
44(1):
25 - 27.
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Xiao and P. Theroux
Clopidogrel inhibits platelet-leukocyte interactions and thrombin receptor agonist peptide-induced platelet activation in patients with an acute coronary syndrome
J. Am. Coll. Cardiol.,
June 2, 2004;
43(11):
1982 - 1988.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Muller, F. Besta, C. Schulz, Z. Li, S. Massberg, and M. Gawaz
Effects of Statins on Platelet Inhibition by a High Loading Dose of Clopidogrel
Circulation,
November 4, 2003;
108(18):
2195 - 2197.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Henderson, S. J. Pocock, T. C. Clayton, R. Knight, K. A. A. Fox, D. G. Julian, D. A. Chamberlain, and Second Randomized Intervention Treatment of Angina
Seven-year outcome in the RITA-2 trial: coronary angioplasty versus medical therapy
J. Am. Coll. Cardiol.,
October 1, 2003;
42(7):
1161 - 1170.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. W. Chan, D. J. Moliterno, P. B. Berger, G. W. Stone, P. M. DiBattiste, S. L. Yakubov, S. K. Sapp, K. Wolski, D. L. Bhatt, E. J. Topol, et al.
Triple antiplatelet therapy during percutaneous coronary intervention is associated withimproved outcomes including one-year survival: Results from the do tirofiban and reoprogive similar efficacy outcome trial (TARGET)
J. Am. Coll. Cardiol.,
October 1, 2003;
42(7):
1188 - 1195.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Jneid, D. L. Bhatt, R. Corti, J. J. Badimon, V. Fuster, and G. S. Francis
Aspirin and Clopidogrel in Acute Coronary Syndromes: Therapeutic Insights From the CURE Study
Arch Intern Med,
May 26, 2003;
163(10):
1145 - 1153.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Mueller, H. Roskamm, F.-J. Neumann, P. Hunziker, S. Marsch, A. Perruchoud, and H. J. Buettner
A randomized comparison of clopidogrel and aspirin versus ticlopidine and aspirin after the placement of coronary artery stents
J. Am. Coll. Cardiol.,
March 19, 2003;
41(6):
969 - 973.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. R. Mehta and S. Yusuf
Short- and long-term oral antiplatelet therapy in acute coronary syndromes and percutaneous coronary intervention
J. Am. Coll. Cardiol.,
February 19, 2003;
41(4_Suppl_S):
79S - 88S.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Alberts, J.D. Easton, G. W. Albers, and P. Amarenco
Clopidogrel Plus Aspirin for Stroke Prevention
Stroke,
November 1, 2002;
33(11):
2546 - 2547.
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. J Redpath and J. R Petrie
Considering Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) Trial: Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation
The British Journal of Diabetes & Vascular Disease,
May 1, 2002;
2(3):
187 - 188.
[PDF]
|
|
|
|
|
|
|
Clopidogrel More Effective Than Ticlopidine After Stenting
Journal Watch Cardiology,
March 1, 2002;
2002(301):
3 - 3.
[Full Text]
|
|
|
|
