Abstract 19503: Durability of Antiplatelet Effect of a Novel Extended-release Formulation of Acetylsalicylic acid, Durlaza in Patients With Diabetes
Background: High platelet turnover (HPT) is implicated in incomplete platelet inhibition and high platelet reactivity (HPR) during immediate release aspirin therapy in type II diabetes patients (T2DM). Durlaza is a new, extended-release orally administered aspirin formulation developed to provide 24-hour antithrombotic effects with once-daily dosing.
Methods: In this open-label, single-center study, T2DM patients (n=40) and a history of cardiovascular disease (CVD) or multiple CVD risk factors were treated with daily 162.5 mg Durlaza for 14±4 days and adverse events were collected. Antiplatelet effects were determined by conventional aggregation (LTA), Multiplate analyzer, thrombelastography with PlateletMapping, PlateletWorks ,VerifyNow Assay, and serum thromboxane B2 (TxB2) at 1, 12, 16, and 24 hrs after the last dose. HPT was defined as immature platelet fraction of ≥3.0% or MPV≥11.0 fl. Patients exhibiting HPT and/or HPR (based on previously published cutpoints in ≥2 assays) were treated with Durlaza at 325mg for 14± 4 days and platelet function testing was repeated.
Results: Prevalence of HPT and HPR was 47% and 27%, respectively. There was no loss of antiplatelet effect at 12, 16 and 24 h versus 1 h by all assays (Table 1). All patients responded to 162.5mg Durlaza as measured by arachidonic acid-induced aggregation with LTA and platelet reactivity levels were low at all timepoints (Table). Serum TxB2 was lower at 12 h (p<0.03) as compared to 1 h after 162.5mg and was lower at all times with the 325 mg vs. the 162.5 mg Durlaza (p < 0.05). HPT did not affect the PD profile of Durlaza (Pts with HPT vs. no HPT, p=NS for all). Patients had no serious adverse events and low treatment related AE rate (<5%).
Conclusion: In this first comprehensive assessment, a new, extended-release 162.5 Durlaza provided sustained antiplatelet effects over 24 h in T2DM patients with a favorable safety profile. Doubling the dose further lowered serum TxB2 in pts with HPT and/or HPR.
Author Disclosures: P.A. Gurbel: Research Grant; Significant; New Haven Pharmaceuticals, Bayer, Daiichi Sankyo, AstraZeneca, Haemonetics, DCRI, HCRI, NIH, Coramed. Other Research Support; Modest; Sinnowa. Speakers Bureau; Modest; AstraZeneca, Daiichi Sankyo, Merck. Honoraria; Modest; AstraZeneca, Daiichi Sankyo, Merck, Jensen. Consultant/Advisory Board; Modest; AstraZeneca, Daiichi Sankyo, Merck. K.P. Bliden: None. J. Patrick: Employment; Significant; New Haven Pharmaceuticals, Inc. K. Saadin: None. U. Tantry: None.
- © 2015 by American Heart Association, Inc.