Author + information
- Received April 3, 2007
- Revision received May 23, 2007
- Accepted May 28, 2007
- Published online October 16, 2007.
- Dominick J. Angiolillo, MD, PhD, FACC⁎,1,3,⁎ (, )
- Esther Bernardo, BSc†,
- Manel Sabaté, MD, PhD†,
- Pilar Jimenez-Quevedo, MD†,
- Marco A. Costa, MD, PhD, FACC⁎,
- Jorge Palazuelos, MD, PhD†,2,
- Rosana Hernández-Antolin, MD, PhD†,
- Raul Moreno, MD†,
- Javier Escaned, MD, PhD†,
- Fernando Alfonso, MD, PhD†,
- Camino Bañuelos, MD†,
- Luis A. Guzman, MD, FACC⁎,
- Theodore A. Bass, MD, FACC⁎,
- Carlos Macaya, MD, PhD† and
- Antonio Fernandez-Ortiz, MD, PhD†
- ↵⁎Reprint requests and correspondence:
Dr. Dominick J. Angiolillo, Division of Cardiology, University of Florida—Shands Jacksonville, 655 West 8th Street, Jacksonville, Florida 32209.
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% Aggmaxbest 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.
↵1 Dr. Angiolillo was the recipient of the 2006 Stop Heart Disease Researcher of the Year Award sponsored by the Florida Heart Research Institute/Florida Chapter of the American College of Cardiology and of the 2007 International Competitive Grants Award sponsored by the GlaxoSmithKline Research and Education Foundation for Cardiovascular Disease.
↵2 Dr. Palazuelos was the recipient of an educational grant from the Spanish Society of Cardiology.
↵3 Dr. Angiolillo is on the Speakers’ Bureau of and is a consultant for Sanofi-Aventis, Bristol-Myers Squibb, and Eli Lilly/Daiichi Sankyo. He has had full access to all study data and had the final responsibility for deciding to submit for publication this manuscript to the Journal of the American College of Cardiology.
Supported in part by a grant from the Fondo de Investigación Sanitaria (FIS 04/1147).
See accompanying online Cardiosource Slide Set.
- Received April 3, 2007.
- Revision received May 23, 2007.
- Accepted May 28, 2007.
- American College of Cardiology Foundation