Antiplatelet Effect Durability of a Novel, 24-Hour, Extended-Release Prescription Formulation of Acetylsalicylic Acid in Patients With Type 2 Diabetes Mellitus

Am J Cardiol. 2016 Dec 15;118(12):1941-1947. doi: 10.1016/j.amjcard.2016.08.088. Epub 2016 Sep 20.

Abstract

High platelet reactivity and high platelet turnover have been implicated in incomplete platelet inhibition during immediate-release acetylsalicylic acid therapy in patients with type 2 diabetes mellitus (DM). An extended-release acetylsalicylic acid (ER-ASA; Durlaza) formulation was developed to provide 24-hour antithrombotic effects with once-daily dosing. The objective of the study was to evaluate the antiplatelet effects of ER-ASA in patients with DM. In this open-label, single-center study, patients with DM (n = 40) and multiple cardiovascular risk factors received ER-ASA 162.5 mg/day for 14 ± 4 days. Multiple platelet function tests, serum and urinary thromboxane B2 metabolites, prostacyclin metabolite, and high-sensitive C-reactive protein levels were assessed at 1, 12, 16, and 24 hours post-dose. Patients with high platelet turnover and/or high platelet reactivity were treated with ER-ASA 325 mg/day for 14 ± 4 days, and laboratory analyses were repeated. All patients responded to ER-ASA 162.5 mg/day as measured by arachidonic acid-induced aggregation, and there was no loss of the platelet inhibitory effect of ER-ASA 162.5 mg/day over 24 hours post-dose (p = not significant). The antiplatelet effect was sustained over 24 hours for all platelet function measurements. Mean 1- to 24-hour serum thromboxane B2 levels were low with both doses and were lower with ER-ASA 325 mg/day compared with 162.5 mg/day therapy (p = 0.002). In conclusion, ER-ASA 162.5 mg daily dose provided sustained antiplatelet effects over 24 hours in patients with type 2 DM and multiple cardiovascular risk factors and had a favorable tolerability profile.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Aged
  • Aspirin / administration & dosage*
  • Aspirin / therapeutic use
  • C-Reactive Protein / metabolism
  • Cardiovascular Diseases / prevention & control*
  • Coronary Artery Disease / complications
  • Coronary Artery Disease / drug therapy*
  • Delayed-Action Preparations
  • Diabetes Mellitus, Type 2 / complications
  • Epoprostenol / biosynthesis
  • Epoprostenol / urine
  • Female
  • Humans
  • Male
  • Manometry
  • Mean Platelet Volume
  • Middle Aged
  • Peripheral Vascular Diseases / complications
  • Peripheral Vascular Diseases / drug therapy*
  • Platelet Aggregation
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Aggregation Inhibitors / therapeutic use
  • Thrombelastography
  • Thromboxane B2 / analogs & derivatives
  • Thromboxane B2 / blood
  • Thromboxane B2 / urine
  • Vasodilation

Substances

  • Delayed-Action Preparations
  • Platelet Aggregation Inhibitors
  • Thromboxane B2
  • 11-dehydro-thromboxane B2
  • C-Reactive Protein
  • Epoprostenol
  • Aspirin