EXPEDITED REVIEW
Late Clinical Events After Clopidogrel Discontinuation May Limit the Benefit of Drug-Eluting Stents
An Observational Study of Drug-Eluting Versus Bare-Metal Stents
Matthias Pfisterer, MD, FACC*,*,
Hans Peter Brunner-La Rocca, MD*,
Peter T. Buser, MD, FACC*,
Peter Rickenbacher, MD ,
Patrick Hunziker, MD ,
Christian Mueller, MD ,
Raban Jeger, MD*,
Franziska Bader, RN*,
Stefan Osswald, MD, FACC*,
Christoph Kaiser, MD* for the BASKET-LATE Investigators
* Departments of Cardiology
Intensive Care Medicine
Internal Medicine, University Hospital
Bruderholzspital, Basel, Switzerland
Manuscript received June 6, 2006;
revised manuscript received August 24, 2006,
accepted August 28, 2006.
* Reprint requests and correspondence: Dr. Matthias Pfisterer, Professor of Cardiology, Head Department of Cardiology, University Hospital, CH-4031 Basel, Switzerland (Email: pfisterer{at}email.ch).
OBJECTIVES: We sought to define the incidence of late clinical events and late stent thrombosis in patients treated with drug-eluting (DES) versus bare-metal stents (BMS) after the discontinuation of clopidogrel as well as their timing and outcome.
BACKGROUND: There is growing concern that delayed endothelialization after DES implantation may lead to late stent thrombosis and related myocardial infarction (MI) or death. However, event rates and outcomes after clopidogrel discontinuation versus BMS are unknown.
METHODS: A consecutive series of 746 nonselected patients with 1,133 stented lesions surviving 6 months without major events were followed for 1 year after the discontinuation of clopidogrel. Patients were assigned randomly 2:1 to DES versus BMS in BASKET (Basel Stent Kosten Effektivitäts Trial). The primary focus of this observation was cardiac death/MI.
RESULTS: Rates of 18-month cardiac death/MI were not different between DES and BMS patients. However, after the discontinuation of clopidogrel (between months 7 and 18), these events occurred in 4.9% after DES versus 1.3% after BMS implantation. Target vessel revascularization remained lower after DES, resulting in similar rates of all clinical events for this time period (DES 9.3%, BMS 7.9%). Documented late stent thrombosis and related death/target vessel MI were twice as frequent after DES versus BMS (2.6% vs. 1.3%). Thrombosis-related events occurred between 15 and 362 days after the discontinuation of clopidogrel, presenting as MI or death in 88%.
CONCLUSIONS: After the discontinuation of clopidogrel, the benefit of DES in reducing target vessel revascularization is maintained but has to be balanced against an increase in late cardiac death or nonfatal MI, possibly related to late stent thrombosis.
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Abbreviations and Acronyms
| | BASKET = Basel Stent Kosten Effektivitäts Trial | | BASKET-LATE = BASKET LAte Thrombotic Events Trial | | BMS = bare-metal stent | | CI = confidence interval | | DES = drug-eluting stent | | HR = hazard ratio | | MI = myocardial infarction | | OR = odds ratio | | TVR = target vessel revascularization |
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|
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R. J. Shemin
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118(23):
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|
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L. O. Jensen, M. Maeng, P. Thayssen, A. Kaltoft, H. H. Tilsted, M. Bottcher, J. F. Lassen, K. N. Hansen, L. R. Krusell, K. Rasmussen, et al.
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1(3):
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|
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|
|
|
|
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Circ Cardiovasc Intervent,
December 1, 2008;
1(3):
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|
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|
|
|
|
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Circ Cardiovasc Intervent,
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1(3):
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|
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|
|
|
|
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M. S. Lee, J. Kobashigawa, and J. Tobis
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December 1, 2008;
1(6):
710 - 715.
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|
|
|
|
|
|
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M. E Pfisterer
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Heart,
December 1, 2008;
94(12):
1648 - 1650.
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[PDF]
|
|
|
|
|
|
|
Authors/writing members, J. Daemen, M. L. Simoons, W. Wijns, A. Bagust, G. Bos, J. M. Bowen, E. Braunwald, E. Camenzind, B. Chevalier, et al.
Meeting Report * ESC Forum on Drug Eluting Stents * European Heart House, Nice, 27-28 September 2007
Eur. Heart J.,
November 26, 2008;
(2008)
ehn510v1.
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Mauri, T. S. Silbaugh, R. E. Wolf, K. Zelevinsky, A. Lovett, Z. Zhou, F. S. Resnic, and S.-L. T. Normand
Long-Term Clinical Outcomes After Drug-Eluting and Bare-Metal Stenting in Massachusetts
Circulation,
October 28, 2008;
118(18):
1817 - 1827.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. B. King III and E. L. Hannan
Mounting Evidence for Safety and Improved Outcomes of Drug-Eluting Stenting: But Is It the Stent?
Circulation,
October 28, 2008;
118(18):
1783 - 1784.
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. A. Lin, R. A. Dudley, F. L. Lucas, D. J. Malenka, E. Vittinghoff, and R. F. Redberg
Frequency of Stress Testing to Document Ischemia Prior to Elective Percutaneous Coronary Intervention
JAMA,
October 15, 2008;
300(15):
1765 - 1773.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Rademacher, A. Knape, J. Schumm, M. Ferrari, A. Lauten, H. Mudra, and H. R. Figulla
Acute and long-term outcome of unprotected left main coronary angioplasty compared to the anticipated surgical risk
Interactive CardioVascular and Thoracic Surgery,
October 1, 2008;
7(5):
871 - 877.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. C. John, R. Wessely, A. Kastrati, A. Schomig, M. Joner, M. Uchihashi, J. Crimins, S. Lajoie, F. D. Kolodgie, H. K. Gold, et al.
Differential Healing Responses in Polymer- and Nonpolymer-Based Sirolimus-Eluting Stents
J. Am. Coll. Cardiol. Intv.,
October 1, 2008;
1(5):
535 - 544.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Wenaweser, J. Daemen, M. Zwahlen, R. van Domburg, P. Juni, S. Vaina, G. Hellige, K. Tsuchida, C. Morger, E. Boersma, et al.
Incidence and Correlates of Drug-Eluting Stent Thrombosis in Routine Clinical Practice: 4-Year Results From a Large 2-Institutional Cohort Study
J. Am. Coll. Cardiol.,
September 30, 2008;
52(14):
1134 - 1140.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. E. Pfisterer
Late Stent Thrombosis After Drug-Eluting Stent Implantation for Acute Myocardial Infarction: A New Red Flag Is Raised
Circulation,
September 9, 2008;
118(11):
1117 - 1119.
[Full Text]
[PDF]
|
|
|
|
|
|
|
Current Guidelines for Preoperative Management Leave Me Wanting More
Journal Watch Hospital Medicine,
August 25, 2008;
2008(825):
1 - 1.
[Full Text]
|
|
|
|
|
|
|
M.-C. Parent and S. Rinfret
The unresolved issues with risk stratification and management of patients with coronary artery disease undergoing major vascular surgery: [Questions non resolues concernant la stratification du risque et la prise en charge des patients atteints de maladie coronarienne subissant une chirurgie vasculaire majeure]
Can J Anesth,
August 1, 2008;
55(8):
542 - 556.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Shinke, J. Li, J. P. Chen, L. Pendyala, T. Goodchild, R. Jabara, S. Geva, T. Ueno, N. Chronos, K. Robinson, et al.
High Incidence of Intramural Thrombus After Overlapping Paclitaxel-Eluting Stent Implantation: Angioscopic and Histopathologic Analysis in Porcine Coronary Arteries
Circ Cardiovasc Intervent,
August 1, 2008;
1(1):
28 - 35.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Austin, K. G. Oldroyd, A. McConnachie, R. Slack, H. Eteiba, A. D. Flapan, K. P. Jennings, R. J. Northcote, A. C.H. Pell, I. R. Starkey, et al.
Drug-Eluting Stents Versus Bare-Metal Stents for Off-Label Indications: A Propensity Score-Matched Outcome Study
Circ Cardiovasc Intervent,
August 1, 2008;
1(1):
45 - 52.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Roy, D. H. Steinberg, S. J. Sushinsky, T. Okabe, T. L. Pinto Slottow, K. Kaneshige, Z. Xue, L. F. Satler, K. M. Kent, W. O. Suddath, et al.
The potential clinical utility of intravascular ultrasound guidance in patients undergoing percutaneous coronary intervention with drug-eluting stents
Eur. Heart J.,
August 1, 2008;
29(15):
1851 - 1857.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. R. Brodie, T. Stuckey, W. Downey, A. Humphrey, B. Bradshaw, C. Metzger, J. Hermiller, F. Krainin, S. Juk, B. Cheek, et al.
Outcomes and Complications With Off-Label Use of Drug-Eluting Stents: Results From the STENT (Strategic Transcatheter Evaluation of New Therapies) Group
J. Am. Coll. Cardiol. Intv.,
August 1, 2008;
1(4):
405 - 414.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. T. Newsome, M. A. Kutcher, and R. L. Royster
Coronary Artery Stents: Part I. Evolution of Percutaneous Coronary Intervention
Anesth. Analg.,
August 1, 2008;
107(2):
552 - 569.
[Abstract]
[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]
|
|
|
|
|
|
|
M. Joner, G. Nakazawa, A. V. Finn, S. C. Quee, L. Coleman, E. Acampado, P. S. Wilson, K. Skorija, Q. Cheng, X. Xu, et al.
Endothelial Cell Recovery Between Comparator Polymer-Based Drug-Eluting Stents
J. Am. Coll. Cardiol.,
July 29, 2008;
52(5):
333 - 342.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. G. Ellis, C. D. O'Shaughnessy, S. L. Martin, K. Kent, T. McGarry, M. A. Turco, D. J. Kereiakes, J. J. Popma, M. Friedman, J. Koglin, et al.
Two-year clinical outcomes after paclitaxel-eluting stent or brachytherapy treatment for bare metal stent restenosis: the TAXUS V ISR trial
Eur. Heart J.,
July 1, 2008;
29(13):
1625 - 1634.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. C Coons and S. Battistone
2007 Guideline Update for Unstable Angina/Non-ST-Segment Elevation Myocardial Infarction: Focus on Antiplatelet and Anticoagulant Therapies
Ann. Pharmacother.,
July 1, 2008;
42(7):
989 - 1001.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. J. Malenka, A. V. Kaplan, F. L. Lucas, S. M. Sharp, and J. S. Skinner
Outcomes Following Coronary Stenting in the Era of Bare-Metal vs the Era of Drug-Eluting Stents
JAMA,
June 25, 2008;
299(24):
2868 - 2876.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Alfonso
The "vulnerable" stent why so dreadful?
J. Am. Coll. Cardiol.,
June 24, 2008;
51(25):
2403 - 2406.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. S. Brett
Coronary Assessment Before Noncardiac Surgery: Current Strategies Are Flawed
Circulation,
June 17, 2008;
117(24):
3145 - 3151.
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Meliga, H. M. Garcia-Garcia, M. Valgimigli, A. Chieffo, G. Biondi-Zoccai, A. O. Maree, S. Cook, L. Reardon, C. Moretti, S. De Servi, et al.
Longest available clinical outcomes after drug-eluting stent implantation for unprotected left main coronary artery disease: the DELFT (Drug Eluting stent for LeFT main) Registry.
J. Am. Coll. Cardiol.,
June 10, 2008;
51(23):
2212 - 2219.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. S. Brar, J. Kim, S. K. Brar, R. Zadegan, M. Ree, I.-L. A. Liu, P. Mansukhani, V. Aharonian, R. Hyett, and A. Y.-J. Shen
Long-term outcomes by clopidogrel duration and stent type in a diabetic population with de novo coronary artery lesions.
J. Am. Coll. Cardiol.,
June 10, 2008;
51(23):
2220 - 2227.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.-H. Choi, A. Prasad, and S. Tsimikas
The evolution of thienopyridine therapy clopidogrel duration, diabetes, and drug-eluting stents.
J. Am. Coll. Cardiol.,
June 10, 2008;
51(23):
2228 - 2229.
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Austin, K. G. Oldroyd, A. McConnachie, R. Slack, H. Eteiba, A. D. Flapan, K. P. Jennings, R. J. Northcote, A. C. H. Pell, I. R. Starkey, et al.
Hospital and operator variations in drug-eluting stent use: a multi-level analysis of 5967 consecutive patients in Scotland
J. Public Health Med.,
June 1, 2008;
30(2):
186 - 193.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. C. Becker, T. W. Meade, P. B. Berger, M. Ezekowitz, C. M. O'Connor, D. A. Vorchheimer, G. H. Guyatt, D. B. Mark, and R. A. Harrington
The Primary and Secondary Prevention of Coronary Artery Disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)
Chest,
June 1, 2008;
133(6_suppl):
776S - 814S.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Kelbaek, L. Klovgaard, S. Helqvist, J. F. Lassen, L. R. Krusell, T. Engstrom, H. E. Botker, E. Jorgensen, K. Saunamaki, S. Aljabbari, et al.
Long-Term Outcome in Patients Treated With Sirolimus-Eluting Stents in Complex Coronary Artery Lesions: 3-Year Results of the SCANDSTENT (Stenting Coronary Arteries in Non-Stress/Benestent Disease) Trial
J. Am. Coll. Cardiol.,
May 27, 2008;
51(21):
2011 - 2016.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Garg, D. J. Cohen, T. Gaziano, and L. Mauri
Balancing the Risks of Restenosis and Stent Thrombosis in Bare-Metal Versus Drug-Eluting Stents: Results of a Decision Analytic Model
J. Am. Coll. Cardiol.,
May 13, 2008;
51(19):
1844 - 1853.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. B. Mark
Interpreting the Music of Drug-Eluting Stents: Halcyon Song or Albatross Dirge?
J. Am. Coll. Cardiol.,
May 13, 2008;
51(19):
1854 - 1856.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. H Bhatt and T. H Hauser
Very Late Stent Thrombosis After Dual Antiplatelet Therapy Discontinuation in a Patient with a History of Acute Stent Thrombosis
Ann. Pharmacother.,
May 1, 2008;
42(5):
708 - 712.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. R. Mulukutla, H. A. Vlachos, O. C. Marroquin, F. Selzer, E. M. Holper, J. D. Abbott, W. K. Laskey, D. O. Williams, C. Smith, W. D. Anderson, et al.
Impact of Drug-Eluting Stents Among Insulin-Treated Diabetic Patients: A Report From the National Heart, Lung, and Blood Institute Dynamic Registry
J. Am. Coll. Cardiol. Intv.,
April 1, 2008;
1(2):
139 - 147.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. L. van der Hoeven, S.-S. Liem, J. Dijkstra, S. C. Bergheanu, H. Putter, M. L. Antoni, D. E. Atsma, M. Bootsma, K. Zeppenfeld, J. W. Jukema, et al.
Stent Malapposition After Sirolimus-Eluting and Bare-Metal Stent Implantation in Patients with ST-Segment Elevation Myocardial Infarction: Acute and 9-Month Intravascular Ultrasound Results of the MISSION! Intervention Study
J. Am. Coll. Cardiol. Intv.,
April 1, 2008;
1(2):
192 - 201.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Zellweger, C. Kaiser, H. P. Brunner-La Rocca, P. T. Buser, S. Osswald, P. Weiss, J. Mueller-Brand, M. E. Pfisterer, and for the BASKET Investigators
Value and Limitations of Target-Vessel Ischemia in Predicting Late Clinical Events After Drug-Eluting Stent Implantation
J. Nucl. Med.,
April 1, 2008;
49(4):
550 - 556.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. T Reaume, R. E Regal, and M. P Dorsch
Indications for Dual Antiplatelet Therapy with Aspirin and Clopidogrel: Evidence-Based Recommendations for Use
Ann. Pharmacother.,
April 1, 2008;
42(4):
550 - 557.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Kelbaek, C. J. Terkelsen, S. Helqvist, J. F. Lassen, P. Clemmensen, L. Klovgaard, A. Kaltoft, T. Engstrom, H. E. Botker, K. Saunamaki, et al.
Randomized comparison of distal protection versus conventional treatment in primary percutaneous coronary intervention: the drug elution and distal protection in ST-elevation myocardial infarction (DEDICATION) trial.
J. Am. Coll. Cardiol.,
March 4, 2008;
51(9):
899 - 905.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Pfisterer, H. P. Brunner-La Rocca, and C. Kaiser
The balance of risks and benefits of drug-eluting versus bare-metal stents.
J. Am. Coll. Cardiol.,
March 4, 2008;
51(9):
972 - 972.
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Thuesen, L. O. Jensen, A. Kaltoft, and M. Maeng
Reply.
J. Am. Coll. Cardiol.,
March 4, 2008;
51(9):
972 - 973.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R Hoffmann, M-C Morice, J W Moses, P J Fitzgerald, L Mauri, G Breithardt, J Schofer, P W Serruys, H-P Stoll, and M B Leon
Impact of late incomplete stent apposition after sirolimus-eluting stent implantation on 4-year clinical events: intravascular ultrasound analysis from the multicentre, randomised, RAVEL, E-SIRIUS and SIRIUS trials
Heart,
March 1, 2008;
94(3):
322 - 328.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Francescone and J. L. Halperin
"Triple Therapy" or Triple Threat?: Balancing the Risks of Antithrombotic Therapy for Patients With Atrial Fibrillation and Coronary Stents
J. Am. Coll. Cardiol.,
February 26, 2008;
51(8):
826 - 827.
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Ortolani, M. Balducelli, P. Marzaroli, G. Piovaccari, A. Menozzi, V. Guiducci, P. Sangiorgio, F. Tarantino, G. Geraci, F. Castriota, et al.
Two-Year Clinical Outcomes With Drug-Eluting Stents for Diabetic Patients With De Novo Coronary Lesions: Results From a Real-World Multicenter Registry
Circulation,
February 19, 2008;
117(7):
923 - 930.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
