Advertisement

Click here for more guidelines.
2012 ACCF/ AATS/ SCAI/ STS Expert Consensus Document on Transcatheter Aortic Valve Replacement
ACCF/ SCAI/ STS/ AATS/ AHA/ ASNC/ HFSA/ SCCT 2012 Appropriate Use Criteria for Coronary Revascularization Focused Update
2012 ACCF/ AHA/ ACR/ SCAI/ SIR/ STS/ SVM/ SVN Key Data Elements and Definitions for Peripheral Atherosclerotic Vascular Disease

 
About JACC CME
Policy on Privacy and Confidentiality
Disclosures
Important Information
 

JACC Imaging Homepage JACC Interventions Homepage
Still not a subscriber to JACC Imaging or JACC Interventions?
Click here
to sign up now!

Submit Manuscripts
Author Information
Subscribe/Renew
Order Reprints
Email Alerts
Feedback
RSS Feed
CME
 
 

Cardiosmart
Cardiosource
CVN
Imaging Library
JACC Imaging
JACC Interventions
 
 

About the Journal
Editorial Board & Staff
 
CME Topic Collections Past Issues Search Current Issue Home
     

J Am Coll Cardiol, 2007; 50:1541-1547, doi:10.1016/j.jacc.2007.05.049 (Published online 1 October 2007).
© 2007 by the American College of Cardiology Foundation
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow View Cardiosource Slide Set
Right arrow View TALK BACK Discussion
Right arrow All Versions of this Article:
j.jacc.2007.05.049v1
50/16/1541    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Angiolillo, D. J.
Right arrow Articles by Fernandez-Ortiz, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Angiolillo, D. J.
Right arrow Articles by Fernandez-Ortiz, A.
Related Collections
Right arrowRelated Article

CLINICAL RESEARCH

Impact of Platelet Reactivity on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease

Dominick J. Angiolillo, MD, PhD, FACC*,*, Esther Bernardo, BSc,{dagger}, Manel Sabaté, MD, PhD{dagger}, Pilar Jimenez-Quevedo, MD{dagger}, Marco A. Costa, MD, PhD, FACC*, Jorge Palazuelos, MD, PhD{dagger}, Rosana Hernández-Antolin, MD, PhD{dagger}, Raul Moreno, MD{dagger}, Javier Escaned, MD, PhD{dagger}, Fernando Alfonso, MD, PhD{dagger}, Camino Bañuelos, MD{dagger}, Luis A. Guzman, MD, FACC*, Theodore A. Bass, MD, FACC*, Carlos Macaya, MD, PhD{dagger} and Antonio Fernandez-Ortiz, MD, PhD{dagger}

* Division of Cardiology, University of Florida College of Medicine—Shands Jacksonville, Jacksonville, Florida
{dagger} Cardiovascular Institute, San Carlos University Hospital, Madrid, Spain

Manuscript received April 3, 2007; revised manuscript received May 23, 2007, accepted May 28, 2007.

* Reprint requests and correspondence: Dr. Dominick J. Angiolillo, Division of Cardiology, University of Florida—Shands Jacksonville, 655 West 8th Street, Jacksonville, Florida 32209. (Email: dominick.angiolillo{at}jax.ufl.edu).

Objectives: This study sought to determine the prognostic implications of high platelet reactivity (HPR) assessed in type 2 diabetes mellitus (T2DM) patients while in their steady-state phase of dual antiplatelet therapy.

Background: Type 2 diabetes mellitus patients have increased platelet reactivity compared with nondiabetic patients. Whether HPR assessed in T2DM while in their steady-state phase of dual antiplatelet therapy is associated with an increased risk of major adverse cardiovascular events (MACE) is unknown.

Methods: Platelet function analyses, which included measures of platelet aggregation and activation, were performed in 173 T2DM patients with coronary artery disease on chronic treatment with aspirin and clopidogrel. The HPR was defined as the upper quartile of maximal platelet aggregation (Aggmax) after 20 µmol/l adenosine diphosphate stimuli. Patients were followed up for 2 years and MACE were recorded.

Results: A total of 41 MACE occurred in 34 patients (19.7%) during the 2-year follow-up. The MACE occurred in 15.2%, 12.2%, 12.2%, and 37.7% of patients from the lowest to upper quartile, respectively (p = 0.005). The HPR was the strongest independent predictor of MACE (hazard ratio 3.35, 95% confidence interval [CI] 1.68 to 6.66, p = 0.001). Receiver-operating characteristic analysis indicated that a cutoff value of 62% Aggmax best predicted MACE (37.8% vs. 13.2%, odds ratio 3.96, 95% CI 1.8 to 8.7, p < 0.001). Patients with HPR had up-regulation of multiple platelet signaling pathways (p < 0.0001 for all assays), indicative of a global hyperreactive platelet status.

Conclusions: High platelet reactivity determined in T2DM patients with coronary artery disease while on chronic dual antiplatelet therapy is associated with a higher risk of long-term adverse cardiovascular events, suggesting the need for tailored antithrombotic drug regimens in these high-risk patients.

Abbreviations and Acronyms
  ADP = adenosine diphosphate
  CAD = coronary artery disease
  HPR = high platelet reactivity
  MACE = major adverse cardiovascular events
  T2DM = type 2 diabetes mellitus


Related Article

Sweet and Sticky: Diabetic Platelets, Enhanced Reactivity, and Cardiovascular Risk
Daniel I. Simon and Alvin H. Schmaier
J. Am. Coll. Cardiol. 2007 50: 1548-1550. [Full Text] [PDF]



This article has been cited by other articles:


Home page
 The Journal of RheumatologyHome page
P. MacMULLAN
Guilty by Association: Platelet Reactivity and Inflammation in Psoriatic Arthritis
J Rheumatol, February 1, 2012; 39(2): 210 - 211.
[Full Text] [PDF]

Home page
 Diabetes and Vascular Disease ResearchHome page
H. M. Hall, S. Banerjee, and D. K. McGuire
Variability of clopidogrel response in patients with type 2 diabetes mellitus
Diabetes and Vascular Disease Research, October 1, 2011; 8(4): 245 - 253.
[Abstract] [PDF]

Home page
 JAMAHome page
G. Parodi, R. Marcucci, R. Valenti, A. M. Gori, A. Migliorini, B. Giusti, P. Buonamici, G. F. Gensini, R. Abbate, and D. Antoniucci
High Residual Platelet Reactivity After Clopidogrel Loading and Long-term Cardiovascular Events Among Patients With Acute Coronary Syndromes Undergoing PCI
JAMA, September 21, 2011; 306(11): 1215 - 1223.
[Abstract] [Full Text] [PDF]

Home page
 Am J Clin NutrHome page
M. Z. Molnar, E. Streja, C. P. Kovesdy, M. J. Budoff, A. R. Nissenson, M. Krishnan, S. D. Anker, K. C. Norris, G. C. Fonarow, and K. Kalantar-Zadeh
High platelet count as a link between renal cachexia and cardiovascular mortality in end-stage renal disease patients
Am J Clin Nutr, September 1, 2011; 94(3): 945 - 954.
[Abstract] [Full Text] [PDF]

Home page
 Eur Heart JHome page
N. Amabile and C. M. Boulanger
Circulating microparticle levels in patients with coronary artery disease: a new indicator of vulnerability?
Eur. Heart J., August 2, 2011; 32(16): 1958 - 1960.
[Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
D. J. Angiolillo, E. Bernardo, M. Zanoni, D. Vivas, P. Capranzano, G. Malerba, D. Capodanno, P. Prandini, A. Pasquali, E. Trabetti, et al.
Impact of Insulin Receptor Substrate-1 Genotypes on Platelet Reactivity and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease
J. Am. Coll. Cardiol., June 28, 2011; 58(1): 30 - 39.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
D. J. Angiolillo
Unraveling Myths of Platelet Function and Genetic Testing: The Road to Making Tailored Antiplatelet Therapy a Reality
J. Am. Coll. Cardiol., June 21, 2011; 57(25): 2484 - 2486.
[Full Text] [PDF]

Home page
 HeartHome page
N. J. Breet, J. W. van Werkum, H. J. Bouman, J. C. Kelder, A. M. Harmsze, C. M. Hackeng, and J. M. ten Berg
High on-treatment platelet reactivity to both aspirin and clopidogrel is associated with the highest risk of adverse events following percutaneous coronary intervention
Heart, June 15, 2011; 97(12): 983 - 990.
[Abstract] [Full Text] [PDF]

Home page
 HeartHome page
D. Vivas, J. C. Garcia-Rubira, E. Bernardo, D. J. Angiolillo, P. Martin, A. Calle-Pascual, I. Nunez-Gil, C. Macaya, and A. Fernandez-Ortiz
Effects of intensive glucose control on platelet reactivity in patients with acute coronary syndromes. Results of the CHIPS Study ("Control de Hiperglucemia y Actividad Plaquetaria en Pacientes con Sindrome Coronario Agudo")
Heart, May 15, 2011; 97(10): 803 - 809.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
R. F. Storey
Exploring Mechanisms of Graft Occlusion: Toward Improved Outcomes in Coronary Artery Bypass Graft Surgery
J. Am. Coll. Cardiol., March 1, 2011; 57(9): 1078 - 1080.
[Full Text] [PDF]

Home page
 CirculationHome page
J. L. Ferreiro and D. J. Angiolillo
Diabetes and Antiplatelet Therapy in Acute Coronary Syndrome
Circulation, February 22, 2011; 123(7): 798 - 813.
[Full Text] [PDF]

Home page
 Eur Heart JHome page
S. James, D. J. Angiolillo, J. H. Cornel, D. Erlinge, S. Husted, F. Kontny, J. Maya, J. C. Nicolau, J. Spinar, R. F. Storey, et al.
Ticagrelor vs. clopidogrel in patients with acute coronary syndromes and diabetes: a substudy from the PLATelet inhibition and patient Outcomes (PLATO) trial
Eur. Heart J., December 2, 2010; 31(24): 3006 - 3016.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
L. Bonello, U. S. Tantry, R. Marcucci, R. Blindt, D. J. Angiolillo, R. Becker, D. L. Bhatt, M. Cattaneo, J. P. Collet, T. Cuisset, et al.
Consensus and Future Directions on the Definition of High On-Treatment Platelet Reactivity to Adenosine Diphosphate
J. Am. Coll. Cardiol., September 14, 2010; 56(12): 919 - 933.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll Cardiol IntvHome page
Y.-H. Jeong, I.-S. Kim, Y. Park, M.-K. Kang, J.-S. Koh, S.-J. Hwang, C. H. Kwak, and J.-Y. Hwang
Carriage of Cytochrome 2C19 Polymorphism Is Associated With Risk of High Post-Treatment Platelet Reactivity on High Maintenance-Dose Clopidogrel of 150 mg/day: Results of the ACCEL-DOUBLE (Accelerated Platelet Inhibition by a Double Dose of Clopidogrel According to Gene Polymorphism) Study
J. Am. Coll. Cardiol. Intv., July 1, 2010; 3(7): 731 - 741.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
W. Hochholzer, D. Trenk, M. F. Fromm, C. M. Valina, C. Stratz, H. P. Bestehorn, H. J. Buttner, and F. J. Neumann
Impact of Cytochrome P450 2C19 Loss-of-Function Polymorphism and of Major Demographic Characteristics on Residual Platelet Function After Loading and Maintenance Treatment With Clopidogrel in Patients Undergoing Elective Coronary Stent Placement
J. Am. Coll. Cardiol., June 1, 2010; 55(22): 2427 - 2434.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll Cardiol IntvHome page
S. E. Ghannudi, P. Ohlmann, N. Meyer, M.-L. Wiesel, B. Radulescu, M. Chauvin, P. Bareiss, C. Gachet, and O. Morel
Impact of P2Y 12 Inhibition by Clopidogrel on Cardiovascular Mortality in Unselected Patients Treated by Percutaneous Coronary Angioplasty: A Prospective Registry
J. Am. Coll. Cardiol. Intv., June 1, 2010; 3(6): 648 - 656.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes CareHome page
P. Gresele, S. Marzotti, G. Guglielmini, S. Momi, S. Giannini, P. Minuz, P. Lucidi, and G. B. Bolli
Hyperglycemia-Induced Platelet Activation in Type 2 Diabetes Is Resistant to Aspirin but Not to a Nitric Oxide-Donating Agent
Diabetes Care, June 1, 2010; 33(6): 1262 - 1268.
[Abstract] [Full Text] [PDF]

Home page
 Eur Heart JHome page
D. Sibbing, N. von Beckerath, T. Morath, J. Stegherr, J. Mehilli, N. Sarafoff, S. Braun, S. Schulz, A. Schomig, and A. Kastrati
Oral anticoagulation with coumarin derivatives and antiplatelet effects of clopidogrel
Eur. Heart J., May 2, 2010; 31(10): 1205 - 1211.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
D. J. Angiolillo, E. Bernardo, D. Capodanno, D. Vivas, M. Sabate, J. L. Ferreiro, M. Ueno, P. Jimenez-Quevedo, F. Alfonso, T. A. Bass, et al.
Impact of Chronic Kidney Disease on Platelet Function Profiles in Diabetes Mellitus Patients With Coronary Artery Disease Taking Dual Antiplatelet Therapy
J. Am. Coll. Cardiol., March 16, 2010; 55(11): 1139 - 1146.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll Cardiol IntvHome page
F. Mangiacapra, E. Barbato, G. Patti, L. Gatto, V. Vizzi, E. Ricottini, A. D'Ambrosio, W. Wijns, and G. Di Sciascio
Point-of-Care Assessment of Platelet Reactivity After Clopidogrel to Predict Myonecrosis in Patients Undergoing Percutaneous Coronary Intervention
J. Am. Coll. Cardiol. Intv., March 1, 2010; 3(3): 318 - 323.
[Abstract] [Full Text] [PDF]

Home page
 Rheumatology (Oxford)Home page
P. A. Mac Mullan, A. J. Peace, A. M. Madigan, A. F. Tedesco, D. Kenny, and G. M. McCarthy
Platelet hyper-reactivity in active inflammatory arthritis is unique to the adenosine diphosphate pathway: a novel finding and potential therapeutic target
Rheumatology, February 1, 2010; 49(2): 240 - 245.
[Abstract] [Full Text] [PDF]

Home page
 Eur Heart JHome page
U. Stenestrand, S. K. James, J. Lindback, O. Frobert, J. Carlsson, F. Schersten, T. Nilsson, B. Lagerqvist, and for the SCAAR/SWEDEHEART study group
Safety and efficacy of drug-eluting vs. bare metal stents in patients with diabetes mellitus: long-term follow-up in the Swedish Coronary Angiography and Angioplasty Registry (SCAAR)
Eur. Heart J., January 2, 2010; 31(2): 177 - 186.
[Abstract] [Full Text] [PDF]

Home page
 Circ Cardiovasc GenetHome page
G. Rudez, H. J. Bouman, J. W. van Werkum, F. W.G. Leebeek, A. Kruit, H. J.T. Ruven, J. M. ten Berg, M. P.M. de Maat, and C. M. Hackeng
Common Variation in the Platelet Receptor P2RY12 Gene Is Associated With Residual On-Clopidogrel Platelet Reactivity in Patients Undergoing Elective Percutaneous Coronary Interventions
Circ Cardiovasc Genet, October 1, 2009; 2(5): 515 - 521.
[Abstract] [Full Text] [PDF]

Home page
 Eur Heart JHome page
C. Verstuyft, T. Simon, and R. B. Kim
Personalized medicine and antiplatelet therapy: ready for prime time?
Eur. Heart J., August 2, 2009; 30(16): 1943 - 1963.
[Full Text] [PDF]

Home page
 CirculationHome page
M. Valgimigli, G. Campo, N. de Cesare, E. Meliga, P. Vranckx, A. Furgieri, D. J. Angiolillo, M. Sabate, M. Hamon, A. Repetto, et al.
Intensifying Platelet Inhibition With Tirofiban in Poor Responders to Aspirin, Clopidogrel, or Both Agents Undergoing Elective Coronary Intervention: Results From the Double-Blind, Prospective, Randomized Tailoring Treatment With Tirofiban in Patients Showing Resistance to Aspirin and/or Resistance to Clopidogrel Study
Circulation, June 30, 2009; 119(25): 3215 - 3222.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
M. J. Price
Bedside Evaluation of Thienopyridine Antiplatelet Therapy
Circulation, May 19, 2009; 119(19): 2625 - 2632.
[Full Text] [PDF]

Home page
 Eur Heart JHome page
F. M. Pulcinelli, L. M. Biasucci, S. Riondino, S. Giubilato, A. Leo, L. Di Renzo, E. Trifiro, T. Mattiello, D. Pitocco, G. Liuzzo, et al.
COX-1 sensitivity and thromboxane A2 production in type 1 and type 2 diabetic patients under chronic aspirin treatment
Eur. Heart J., May 2, 2009; 30(10): 1279 - 1286.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes CareHome page
D. J. Angiolillo
Antiplatelet Therapy in Diabetes: Efficacy and Limitations of Current Treatment Strategies and Future Directions
Diabetes Care, April 1, 2009; 32(4): 531 - 540.
[Full Text] [PDF]

Home page
 Cleveland Clinic Journal of MedicineHome page
K. KOTTKE-MARCHANT
Importance of platelets and platelet response in acute coronary syndromes
Cleveland Clinic Journal of Medicine, April 1, 2009; 76(Suppl_1): S2 - S7.
[Abstract] [Full Text] [PDF]

Home page
 Eur Heart JHome page
W. Kuliczkowski, A. Witkowski, L. Polonski, C. Watala, K. Filipiak, A. Budaj, J. Golanski, D. Sitkiewicz, J. Pregowski, J. Gorski, et al.
Interindividual variability in the response to oral antiplatelet drugs: a position paper of the Working Group on antiplatelet drugs resistance appointed by the Section of Cardiovascular Interventions of the Polish Cardiac Society, endorsed by the Working Group on Thrombosis of the European Society of Cardiology
Eur. Heart J., February 2, 2009; 30(4): 426 - 435.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Chem.Home page
L. M. Biasucci, G. Liuzzo, R. Della Bona, M. Leo, G. Biasillo, D. J. Angiolillo, A. Abbate, V. Rizzello, G. Niccoli, S. Giubilato, et al.
Different Apparent Prognostic Value of hsCRP in Type 2 Diabetic and Nondiabetic Patients with Acute Coronary Syndromes
Clin. Chem., February 1, 2009; 55(2): 365 - 368.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
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]

Home page
 J Am Coll CardiolHome page
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]

Home page
 Ther Adv Cardiovasc DisHome page
L. Ang and E. Mahmud
Monitoring oral antiplatelet therapy: is it justified?
Therapeutic Advances in Cardiovascular Disease, December 1, 2008; 2(6): 485 - 496.
[Abstract] [PDF]

Home page
 CirculationHome page
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]

Home page
 J Am Coll CardiolHome page
D. L. Bhatt
What Makes Platelets Angry: Diabetes, Fibrinogen, Obesity, and Impaired Response to Antiplatelet Therapy?
J. Am. Coll. Cardiol., September 23, 2008; 52(13): 1060 - 1061.
[Full Text] [PDF]

Home page
 CirculationHome page
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]

Home page
 Eur Heart JHome page
D. J. Angiolillo, P. Capranzano, S. Goto, M. Aslam, B. Desai, R. K. Charlton, Y. Suzuki, L. C. Box, S. B. Shoemaker, M. M. Zenni, et al.
A randomized study assessing the impact of cilostazol on platelet function profiles in patients with diabetes mellitus and coronary artery disease on dual antiplatelet therapy: results of the OPTIMUS-2 study
Eur. Heart J., September 2, 2008; 29(18): 2202 - 2211.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
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]

Home page
 J Am Coll CardiolHome page
A. N. DeMaria, J. J. Bax, O. Ben-Yehuda, P. Clopton, G. K. Feld, G. S. Ginsburg, B. H. Greenberg, J. D. Knoke, W. Y.W. Lew, J. A.C. Lima, et al.
Highlights of the Year in JACC 2007
J. Am. Coll. Cardiol., January 29, 2008; 51(4): 490 - 512.
[Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
D. I. Simon and A. H. Schmaier
Sweet and Sticky: Diabetic Platelets, Enhanced Reactivity, and Cardiovascular Risk
J. Am. Coll. Cardiol., October 16, 2007; 50(16): 1548 - 1550.
[Full Text] [PDF]


 
  CME Topic Collections Past Issues Search Current Issue Home

Advertisement