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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,, Manel Sabaté, MD, PhD, Pilar Jimenez-Quevedo, MD, Marco A. Costa, MD, PhD, FACC^_*, Jorge Palazuelos, MD, PhD, 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

^_* Division of Cardiology, University of Florida College of Medicine—Shands Jacksonville, Jacksonville, Florida
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 (Agg_max) 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% Agg_max 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

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