Author + information
- Received February 6, 2011
- Revision received May 2, 2011
- Accepted May 6, 2011
- Published online August 1, 2011.
- Masafumi Ueno, MD⁎,
- José L. Ferreiro, MD⁎,
- Salvatore D. Tomasello, MD⁎,
- Antonio Tello-Montoliu, MD, PhD⁎,
- Davide Capodanno, MD⁎,
- Naveen Seecheran, MD⁎,
- Murali Kodali, MD⁎,
- Kodlipet Dharmashankar, MD⁎,
- Bhaloo Desai, PhD⁎,
- Ronald K. Charlton, PhD†,
- Theodore A. Bass, MD⁎ and
- Dominick J. Angiolillo, MD, PhD⁎,⁎ ()
- ↵⁎Reprint requests and correspondence
: Dr. Dominick J. Angiolillo, University of Florida College of Medicine-Jacksonville, 655 West 8th Street, Jacksonville, Florida 32209
Objectives The aim of this study was to evaluate the impact of the phosphodiesterase (PDE) inhibitor pentoxifylline on platelet function profiles in patients receiving dual antiplatelet therapy (DAPT).
Background Previous studies have shown that, in patients receiving DAPT, the adjunctive use of a PDE inhibitor enhances platelet inhibition, particularly in those presenting with diabetes mellitus (DM). However, the pharmacodynamic (PD) effects of the PDE inhibitor pentoxifylline on platelet function profiles in DM patients receiving DAPT are unknown.
Methods This was a prospective, randomized, double-blind, parallel design study conducted in DM patients with stable coronary artery disease receiving DAPT. Patients were randomly assigned to either pentoxifylline 400 mg or placebo 3 times daily for 14 days. The PD effects were assessed by vasodilator-stimulated phosphoprotein phosphorylation assay, light transmittance aggregometry, VerifyNow P2Y12 assay (Accumetric, Inc., San Diego, California), and multiple electrode aggregometry at baseline and 14 days. The PD effects were also assessed according the presence or absence of high on-treatment platelet reactivity status.
Results A total of 40 patients were available for analysis. At 14 days, there were no differences in the P2Y12 reactivity index as assessed by vasodilator-stimulated phosphoprotein phosphorylation between treatment groups (primary endpoint; p = 0.93). Intra-group comparisons also failed to show any differences between baseline and 14-day P2Y12 reactivity index assessment in the placebo and pentoxifylline arms (p = 0.61). There were no significant inter- and intra-group differences in all other PD measures. The PD effects did not vary according the presence or absence of high on-treatment platelet reactivity.
Conclusions Adjunctive treatment with pentoxifylline is not associated with increased platelet inhibitory effects in DM patients with coronary artery disease receiving DAPT.
Dr. Ferreiro reports receiving honoraria for lectures from Daiichi Sankyo, Inc., and Eli Lilly Company. Dr. Bass reports receiving honoraria for lectures from Eli Lilly Company and Daiichi Sankyo, Inc.; consulting fees from Eli Lilly Company and Daiichi Sankyo, Inc.; and research grants from Baxter. Dr. Angiolillo reports receiving honoraria/lectures from Bristol-Myers Squibb/Sanofi-Aventis, Eli Lilly Co., and Daiichi Sankyo, Inc.; honoraria/advisory board for Bristol-Myers Squibb/Sanofi-Aventis, Eli Lilly Co., Daiichi Sankyo, Inc., The Medicines Company, Portola, Novartis, Medicure, Accumetrics, Arena Pharmaceuticals, AstraZeneca, Merck, and Evolva; and research grants from Bristol-Myers Squibb/Sanofi-Aventis, GlaxoSmithKline, Otsuka, Boston Scientific, Eli Lilly Co., Daiichi Sankyo, Inc., The Medicines Company, Portola, Accumetrics, Schering-Plough, AstraZeneca, Eisai, and Johnson & Johnson. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received February 6, 2011.
- Revision received May 2, 2011.
- Accepted May 6, 2011.
- American College of Cardiology Foundation