CLINICAL RESEARCH: INTERVENTIONAL CARDIOLOGY
Impact of the Degree of Peri-Interventional Platelet Inhibition After Loading With Clopidogrel on Early Clinical Outcome of Elective Coronary Stent Placement
Willibald Hochholzer, MD*,
Dietmar Trenk, PhD*,
Hans-Peter Bestehorn, MD*,
Benjamin Fischer*,
Christian M. Valina, MD*,
Miroslaw Ferenc, MD*,
Michael Gick, MD*,
Angelika Caputo, PhD ,
Heinz Joachim Büttner, MD* and
Franz-Josef Neumann, MD*,*
* Herz-Zentrum Bad Krozingen, Bad Krozingen, Germany
Institut für Medizinische Biometrie und Medizinische Informatik, University of Freiburg, Freiburg, Germany
Manuscript received December 8, 2005;
revised manuscript received May 30, 2006,
accepted June 6, 2006.
* Reprint requests and correspondence: Dr. Franz-Josef Neumann, Herz-Zentrum Bad Krozingen, Suedring 15, 79189 Bad Krozingen, Germany. (Email: franz-josef.neumann{at}herzzentrum.de).
OBJECTIVES: Our prospective study tested the hypothesis that the 30-day clinical outcome of elective percutaneous catheter intervention (PCI) differs between strata defined by quartiles of platelet aggregation after loading with 600 mg clopidogrel.
BACKGROUND: Platelet responses after loading with clopidogrel are highly variable. The impact of this variability on the peri-interventional risk of patients undergoing PCI has not been investigated prospectively.
METHODS: Our study included 802 consecutive patients undergoing elective coronary stent placement. Before PCI, patients received a loading dose of 600 mg clopidogrel followed by 75 mg daily. Primary end point was the 30-day composite of death, myocardial infarction, and target lesion revascularization (major adverse cardiac events [MACE]). Platelet aggregation was assessed immediately before PCI by optical aggregometry (5 µmol/l adenosine diphosphate).
RESULTS: During 30-day follow-up, 15 patients (1.9%) incurred MACE (3 deaths, 8 myocardial infarctions, 8 target lesion revascularizations). Quartiles of platelet aggregation were <4%, 4% to 14%, 15% to 32%, and >32%. Thirty-day MACE differed significantly (p = 0.034) between quartiles of platelet aggregation. It was 0.5% in the first quartile, 0.5% in the second, 3.1% in the third, and 3.5% in the fourth. Platelet aggregation above the median carried a 6.7-fold risk (95% confidence interval 1.52 to 29.41; p = 0.003) of 30-day MACE. Multivariable logistic regression analysis, including pertinent covariables, confirmed platelet aggregation as a significant independent predictor of 30-day MACE (adjusted odds ratio per 10% increase in platelet aggregation 1.32, 95% confidence interval 1.04 to 1.61; p = 0.026).
CONCLUSIONS: The level of platelet aggregation immediately before elective coronary stenting in patients pre-treated with a high loading dose of clopidogrel is correlated with early outcome after the procedure.
|
Abbreviations and Acronyms
| | ADP = adenosine diphosphate | | AHA/ACC = American Heart Association/American College of Cardiology | | EXCELSIOR = Impact of Extent of Clopidogrel-Induced Platelet Inhibition During Elective Stent Implantation on Clinical Event Rate | | GP = glycoprotein | | MACE = major adverse cardiac event | | MI = myocardial infarction | | PCI = percutaneous catheter intervention | | TIMI = Thrombolysis In Myocardial Infarction |
|
Related Article
-
Platelet Function Assessment to Predict Outcomes After Coronary Interventions: Hype or Hope?
- Fernando Alfonso and Dominick J. Angiolillo
J. Am. Coll. Cardiol. 2006 48: 1751-1754.
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
D. Erlinge, C. Varenhorst, O. O. Braun, S. James, K. J. Winters, J. A. Jakubowski, J. T. Brandt, A. Sugidachi, A. Siegbahn, and L. Wallentin
Patients With Poor Responsiveness to Thienopyridine Treatment or With Diabetes Have Lower Levels of Circulating Active Metabolite, but Their Platelets Respond Normally to Active Metabolite Added Ex Vivo
J. Am. Coll. Cardiol.,
December 9, 2008;
52(24):
1968 - 1977.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Cairns and J. Eikelboom
The Pursuit of Clinically Relevant Measures of Platelet Function After Antiplatelet Drug Therapy
J. Am. Coll. Cardiol.,
December 9, 2008;
52(24):
1978 - 1980.
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Patti, A. Nusca, F. Mangiacapra, L. Gatto, A. D'Ambrosio, and G. Di Sciascio
Point-of-Care Measurement of Clopidogrel Responsiveness Predicts Clinical Outcome in Patients Undergoing Percutaneous Coronary Intervention: Results of the ARMYDA-PRO (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Platelet Reactivity Predicts Outcome) Study
J. Am. Coll. Cardiol.,
September 30, 2008;
52(14):
1128 - 1133.
[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]
|
|
|
|
|
|
|
A. M. Gori, R. Marcucci, A. Migliorini, R. Valenti, G. Moschi, R. Paniccia, P. Buonamici, G. F. Gensini, R. Vergara, R. Abbate, et al.
Incidence and Clinical Impact of Dual Nonresponsiveness to Aspirin and Clopidogrel in Patients With Drug-Eluting Stents
J. Am. Coll. Cardiol.,
August 26, 2008;
52(9):
734 - 739.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Trenk and F.-J. Neumann
Aspirin Resistance: An Underestimated Risk in Patients With Drug-Eluting Stents?
J. Am. Coll. Cardiol.,
August 26, 2008;
52(9):
740 - 742.
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. T. Newsome, R. S. Weller, J. C. Gerancher, M. A. Kutcher, and R. L. Royster
Coronary Artery Stents: II. Perioperative Considerations and Management
Anesth. Analg.,
August 1, 2008;
107(2):
570 - 590.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Geisler, C. Zurn, M. Paterok, K. Gohring-Frischholz, B. Bigalke, K. Stellos, P. Seizer, B. F. Kraemer, J. Dippon, A. E. May, et al.
Statins do not adversely affect post-interventional residual platelet aggregation and outcomes in patients undergoing coronary stenting treated by dual antiplatelet therapy
Eur. Heart J.,
July 1, 2008;
29(13):
1635 - 1643.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Widimsky, Z. Motovska, S. Simek, P. Kala, R. Pudil, F. Holm, R. Petr, D. Bilkova, H. Skalicka, P. Kuchynka, et al.
Clopidogrel pre-treatment in stable angina: for all patients >6 h before elective coronary angiography or only for angiographically selected patients a few minutes before PCI? A randomized multicentre trial PRAGUE-8
Eur. Heart J.,
June 2, 2008;
29(12):
1495 - 1503.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Sibbing, G. Busch, S. Braun, S. Jawansky, A. Schomig, A. Kastrati, I. Ott, and N. von Beckerath
Impact of bivalirudin or unfractionated heparin on platelet aggregation in patients pretreated with 600 mg clopidogrel undergoing elective percutaneous coronary intervention
Eur. Heart J.,
June 2, 2008;
29(12):
1504 - 1509.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T Geisler, M Kapp, K Gohring-Frischholz, K Daub, C Dosch, B Bigalke, H Langer, C Herdeg, and M Gawaz
Residual platelet activity is increased in clopidogrel- and ASA-treated patients with coronary stenting for acute coronary syndromes compared with stable coronary artery disease
Heart,
June 1, 2008;
94(6):
743 - 747.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Trenk, W. Hochholzer, M. F. Fromm, L.-E. Chialda, A. Pahl, C. M. Valina, C. Stratz, P. Schmiebusch, H.-P. Bestehorn, H. J. Buttner, et al.
Cytochrome P450 2C19 681G>A Polymorphism and High On-Clopidogrel Platelet Reactivity Associated With Adverse 1-Year Clinical Outcome of Elective Percutaneous Coronary Intervention With Drug-Eluting or Bare-Metal Stents
J. Am. Coll. Cardiol.,
May 20, 2008;
51(20):
1925 - 1934.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Cairns and J. Eikelboom
Clopidogrel Resistance: More Grist for the Mill
J. Am. Coll. Cardiol.,
May 20, 2008;
51(20):
1935 - 1937.
[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]
|
|
|
|
|
|
|
L. Wallentin
Dual antiplatelet therapy in the drug-eluting stent era
Eur. Heart J. Suppl.,
May 1, 2008;
10(suppl_D):
D38 - D44.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Price, S. Endemann, R. R. Gollapudi, R. Valencia, C. T. Stinis, J. P. Levisay, A. Ernst, N. S. Sawhney, R. A. Schatz, and P. S. Teirstein
Prognostic significance of post-clopidogrel platelet reactivity assessed by a point-of-care assay on thrombotic events after drug-eluting stent implantation
Eur. Heart J.,
April 2, 2008;
29(8):
992 - 1000.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Muller-Schunk, J. Linn, N. Peters, M. Spannagl, M. Deisenberg, H. Bruckmann, and T.E. Mayer
Monitoring of Clopidogrel-Related Platelet Inhibition: Correlation of Nonresponse with Clinical Outcome in Supra-Aortic Stenting
AJNR Am. J. Neuroradiol.,
April 1, 2008;
29(4):
786 - 791.
[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]
|
|
|
|
|
|
|
P. L. L'Allier, G. Ducrocq, N. Pranno, S. Noble, R. Ibrahim, J. C. Gregoire, F. Azzari, A. Nozza, C. Berry, S. Doucet, et al.
Clopidogrel 600-mg double loading dose achieves stronger platelet inhibition than conventional regimens: results from the PREPAIR randomized study.
J. Am. Coll. Cardiol.,
March 18, 2008;
51(11):
1066 - 1072.
[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]
|
|
|
|
|
|
|
K. E. Kip, K. Hollabaugh, O. C. Marroquin, and D. O. Williams
The Problem With Composite End Points in Cardiovascular Studies The Story of Major Adverse Cardiac Events and Percutaneous Coronary Intervention.
J. Am. Coll. Cardiol.,
February 19, 2008;
51(7):
701 - 707.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. D. Wiviott, D. Trenk, A. L. Frelinger, M. O'Donoghue, F.-J. Neumann, A. D. Michelson, D. J. Angiolillo, H. Hod, G. Montalescot, D. L. Miller, 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,
December 18, 2007;
116(25):
2923 - 2932.
[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]
|
|
|
|
|
|
|
P. A. Gurbel, R. C. Becker, K. G. Mann, S. R. Steinhubl, and A. D. Michelson
Platelet Function Monitoring in Patients With Coronary Artery Disease
J. Am. Coll. Cardiol.,
November 6, 2007;
50(19):
1822 - 1834.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. J. Angiolillo, E. Bernardo, M. Sabate, P. Jimenez-Quevedo, M. A. Costa, J. Palazuelos, R. Hernandez-Antolin, R. Moreno, J. Escaned, F. Alfonso, et al.
Impact of Platelet Reactivity on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease
J. Am. Coll. Cardiol.,
October 16, 2007;
50(16):
1541 - 1547.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Campo, M. Valgimigli, D. Gemmati, G. Percoco, L. Catozzi, A. Frangione, F. Federici, F. Ferrari, M. Tebaldi, S. Luccarelli, et al.
Poor Responsiveness to Clopidogrel: Drug-Specific or Class-Effect Mechanism?: Evidence From a Clopidogrel-to-Ticlopidine Crossover Study
J. Am. Coll. Cardiol.,
September 18, 2007;
50(12):
1132 - 1137.
[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]
|
|
|
|
|
|
|
N. von Beckerath, A. Kastrati, A. Wieczorek, G. Pogatsa-Murray, D. Sibbing, I. Graf, and A. Schomig
A double-blind, randomized study on platelet aggregation in patients treated with a daily dose of 150 or 75 mg of clopidogrel for 30 days
Eur. Heart J.,
August 1, 2007;
28(15):
1814 - 1819.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. R. Dixon, C. L. Grines, and W. W. O'Neill
The Year in Interventional Cardiology
J. Am. Coll. Cardiol.,
July 17, 2007;
50(3):
270 - 285.
[Full Text]
[PDF]
|
|
|
|
|
|
|
Authors/Task Force Members, J.-P. Bassand, C. W. Hamm, D. Ardissino, E. Boersma, A. Budaj, F. Fernandez-Aviles, K. A.A. Fox, D. Hasdai, E. M. Ohman, et al.
Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes: The Task Force for the Diagnosis and Treatment of Non-ST-Segment Elevation Acute Coronary Syndromes of the European Society of Cardiology
Eur. Heart J.,
July 1, 2007;
28(13):
1598 - 1660.
[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]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
D. J. Angiolillo, S. B. Shoemaker, B. Desai, H. Yuan, R. K. Charlton, E. Bernardo, M. M. Zenni, L. A. Guzman, T. A. Bass, and M. A. Costa
Randomized Comparison of a High Clopidogrel Maintenance Dose in Patients With Diabetes Mellitus and Coronary Artery Disease: Results of the Optimizing Antiplatelet Therapy in Diabetes Mellitus (OPTIMUS) Study
Circulation,
February 13, 2007;
115(6):
708 - 716.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Daniel, T. Pinter, I. G Horvath, and A. Komocsi
Variability in response to clopidogrel: where is the threshold for 'low response'?
Eur. Heart J.,
February 8, 2007;
(2007)
ehl499v1.
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. J. Kereiakes
Does Clopidogrel Each Day Keep Stent Thrombosis Away?
JAMA,
January 10, 2007;
297(2):
209 - 211.
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Alfonso and D. J. Angiolillo
Platelet Function Assessment to Predict Outcomes After Coronary Interventions: Hype or Hope?
J. Am. Coll. Cardiol.,
November 7, 2006;
48(9):
1751 - 1754.
[Full Text]
[PDF]
|
|
|
|
