Enteric-coated aspirin may not be completely absorbed in T2DM

Last Updated: 2017-02-28

By Lorraine L. Janeczko

NEW YORK (Reuters Health) – Patients with type 2 diabetes mellitus (T2DM) may not completely absorb enteric-coated aspirin, a small randomized trial suggests.

"The enteric coating in aspirin may interfere with aspirin’s antiplatelet effect, at least in the first few days of therapy, likely due to issues of absorption," lead author Dr. Deepak L. Bhatt of Brigham and Women’s Hospital Heart and Vascular Center and Harvard Medical School in Boston told Reuters Health.

"Older data do not clearly show a benefit of enteric coating on reducing the risk of gastrointestinal bleeding, though in some patients, it may help with subjective dyspepsia. Thus, the lack of any huge benefit needs to be weighed against the potential diminution in early antiplatelet effect that we identified in our small, but carefully done, randomized trial," Dr. Bhatt said in an email.

"Aspirin is a very commonly used medication for secondary and primary prevention of cardiovascular events. As such, anything that may affect aspirin’s antiplatelet properties even by a small amount could have broad ramifications," he noted.

As reported February 14 in the Journal of the American College of Cardiology, researchers measured the rate and extent of serum thromboxane generation and aspirin pharmacokinetics in 40 patients with diabetes in a single-blind, triple-crossover study.

Patients were given three 325-mg aspirin formulations: plain aspirin, PL2200 (a modified-release lipid-based aspirin), and delayed-release EC aspirin. Antiplatelet activity onset was measured by the rate and extent of inhibition of serum thromboxane B2 (TXB2) generation. Aspirin nonresponsiveness was considered to be a level of residual serum TXB2 associated with increased thrombotic risk (<99.0% inhibition or TXB2>3.1 ng/ml) within 72 hours of taking three daily aspirin doses.

The authors enrolled 40 obese patients who ranged in age from 21 to 79; 65% were male. Patients had T2DM not requiring insulin and no history of vascular disease; overall, 35 participants completed all three crossover phases.

Participants were not allowed to take nonsteroidal anti-inflammatory drugs, antisecretory agents, antacids, or salicylate-containing nutritional supplements within two weeks of randomization; and all participants were tested for normal platelet function with arachidonic acid-induced platelet aggregation response.

Nonresponsiveness rates with plain aspirin, PL2200, and EC aspirin were 15.8%, 8.1%, and 52.8%, respectively (p<0.001 for both comparisons compared with EC aspirin; p=0.30 comparing plain aspirin and PL2200).

Also, 56% patients treated with EC aspirin had serum TXB2 levels over 3.1 ng/ml compared with 18% and 11% of patients after they were given plain aspirin and PL2200 (p<0.0001).

Compared with plain aspirin and PL2200, the high nonresponsiveness rate with EC aspirin was linked with lower exposure to acetylsalicylic acid (63% and 70% lower geometric mean maximum plasma concentration; 77% and 82% lower area under the curve from time 0 to the last time measured); and 66% and 72% lower maximal decrease of TXB2, with high variability between patients.

Dr. Carlo Patrono of Catholic University School of Medicine in Rome, Italy, said in an email, "The lack of a control group of obese, non-diabetic subjects makes it difficult to assess the contribution of diabetes versus obesity to the observed pharmacokinetic/pharmacodynamic differences among different 325-mg aspirin formulations.”

"Moreover, the study did not examine the effects of chronic administration of low-dose (i.e., 75 to 100 mg) EC aspirin, which was previously shown to reverse the non-responsiveness to a single 325-mg dose of EC aspirin to a full response," said Dr. Patrono, who co-wrote an editorial about the study with Dr. Bianca Rocca, also of Catholic University School of Medicine in Rome.

"Obesity and diabetes are independent and probably additive determinants of poor responsiveness to low-dose aspirin, limiting the extent and/or duration of platelet thromboxane suppression, and most likely requiring different dosing strategies to optimize antiplatelet therapy in patients with these metabolic disorders," Dr. Patrono said.

Considering further related research, Dr. Bhatt said in an email, "Ideally, the impact of our pharmacokinetics/pharmacodynamics trial needs to be evaluated in a clinical trial powered for cardiovascular outcomes – which may or may not ever be performed. Nevertheless, it provides a word of caution about use of enteric-coated aspirin, especially in those situations where early antiplatelet effect is deemed necessary."

PLx Pharma, makers of the PL2200 aspirin, funded the study.

SOURCES: http://bit.ly/2lTlOht and http://bit.ly/2lvwUbw

J Am Coll Cardiol 2017.