Enteric coating associated with aspirin nonresponsiveness in patients with type 2 diabetes
medwireNews: Study results suggest that enteric-coated (EC) aspirin is associated with a lower platelet response than either plain or lipid-based formulations in obese patients with type 2 diabetes.
“Although the clinical implications need to be established, this finding does raise potential concerns that patients taking EC aspirin may not receive the full cardioprotective benefit of this important drug,” write the study authors in the Journal of the American College of Cardiology.
In a triple-crossover pharmacokinetic (PK) and pharmacodynamic (PD) trial, patients with type 2 diabetes and no history of cardiovascular disease were randomly allocated to receive plain aspirin, the modified-release lipid-based aspirin PL2200, or a delayed-release EC formulation, at a dose of 325 mg once daily. A total of 35 patients received all three aspirin formulations over the course of the study.
The rate of aspirin nonresponsiveness – defined as patients who did not reach 99% inhibition of serum thromboxane B2 (TXB2) formation or a minimum concentration above 3.1 ng/mL within 72 hours after three daily aspirin doses – was significantly higher among patients receiving EC aspirin compared with plain aspirin or PL2200, with corresponding rates of 52.8%, 15.8%, and 8.1%.
Treatment with either plain aspirin or PL2200 resulted in significantly faster inhibition of TXB2 than EC aspirin, indicated by times to 99% inhibition of 16.7 hours, 12.5 hours, and 48.2 hours, respectively.
Furthermore, the maximum concentration (Cmax) of acetylsalicylic acid was significantly lower, and the time to Cmax significantly longer, in patients receiving EC aspirin compared with plain aspirin or PL220 (539 vs 1442 and 1803 ng/mL, and 3.5 vs 1.1 and 1.3 hours, respectively),
These findings indicate that “the use of EC aspirin was associated with greater nonresponsiveness due to reduced bioavailability” than either plain aspirin or PL220, report Deepak Bhatt (Brigham and Women’s Hospital Heart & Vascular Center and Harvard Medical School, Boston, Massachusetts, USA) and colleagues.
However, Carlo Patrono and Bianca Rocca (both from Catholic University School of Medicine, Rome, Italy) caution in an accompanying editorial that the study “did not examine the effects of chronic administration of low-dose EC aspirin, which was previously shown to reverse the nonresponsiveness to a single 325-mg dose of EC aspirin to a full response.”
And they add that a low 75 to 100 mg daily dose of aspirin and chronic dosing “more thoroughly reflect recommended clinical practice” than three consecutive daily doses of 325 mg.
The editorialists explain that “diabetes and obesity are independent and possibly additive determinants of poor aspirin responsiveness,” but note that “the lack of a control group of matched obese, nondiabetic subjects precludes assessing the contribution of obesity versus diabetes to the observed PK/PD differences” in the current study.
medwireNews is an independent medical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2017