Isabella Russo, PhD, a researcher at the University of Turin, Italy reported that, after 3 months of therapy, men found to be resistant to aspirin had significantly improved their closing time on the PFA-100 test of aspirin resistance from 150 seconds to over 200 seconds – the threshold for aspirin resistance (P=0.028).
Glucose-lowering therapies did not, however, alter status in men who were aspirin sensitive at baseline.
In her oral presentation at the annual meeting of the European Association for the Study of Diabetes, Russo noted that aspirin therapy is associated with a 25% reduction in cardiac events, but the cardiovascular benefit of aspirin in diabetes patients with cardiovascular risk appears to be lower.
"Several mechanisms of action can be proposed to account for the reduced aspirin effects in type 2 diabetes. The role of blood glucose control on platelet sensitivity to aspirin, however, has been poorly investigated," she said in her oral presentation.
Russo and her research team noted that hints from in vitro studies using aspirin healthy subjects suggested that aspirin resistance might be related to glucose-induced increase of oxidative stress.
They tested this theory by recruiting 37 men diagnosed with type 2 diabetes and a glycated hemoglobin A1c of 7.5% or greater while on metformin therapy with or without other oral medications.
The men in the study were about 61 years of age and had a body mass index of 29.6 kg/m2. The average baseline HbA1c was 8.9%.
The men were not taking other antiplatelet drugs and all participants were free of acute coronary syndrome events or revascularization for at least three months prior to entry into the study.
The participants were administered a 3-month course of intensive glucose lowering, including insulin if necessary. They then underwent tests to determine aspirin sensitivity. At baseline, 27 of the men were determined to have aspirin sensitivity and 10 men (27%) were determined to be aspirin resistant.
Men who were aspirin resistant had double the level of thromboxane as those who were aspirin sensitive. Moreover, this cohort all had elevated biomarkers of inflammation.
The men who were aspirin resistant at baseline had significantly higher total cholesterol (P=0.009), LDL-cholesterol (P=0.050), non HDL-cholesterol (P=0.011), and APO-B100 (P=0.009) than men who were aspirin sensitive.
They were treated with metformin, insulin, sulfonylureas, and dipeptidyl peptidase 4 inhibitors as needed to achieve glucose control.
The aspirin-resistant men reduced HbA1c by 1.6% (P<0.0001); reduced fasting blood glucose 47 mg/dl (P<0.001); reduced their postprandial blood glucose 38 mg/dl (P=0.009); and also reduced several cytokines measures associated with inflammation, Russo demonstrated.
"We showed that a 3-month intervention program designed to improve blood glucose control improves aspirin sensitivity in aspirin-resistant patients," Russo said. She said the study also shows that "in the presence of aspirin resistance, a strong correlation exists between the degree of platelet insensitivity to aspirin and markers of glycemic control."
Gerit-Holger Schernthaner, MD, PhD, professor of medicine at the Medical University of Vienna, said, "In early diabetes, aspirin resistance is not a major problem, but after many years of having diabetes, the risk of developing cardiovascular disease is very high. And then the probability of having aspirin resistance might be more frequent than you would think. In this study it was 27% and this is quite high."
"We do know from some studies in the cardiology field that aspirin resistance is not so infrequent. Dr. Russo did not answer the question of what happens in patients who have a shorter period of diabetes or those who might be resistant to prasugrel or clopidogrel. This could be quite important."
- The study found that a short-term improvement of blood glucose control in men with type 2 diabetes reduced aspirin resistance as measured by platelet sensitivity to aspirin.
- This study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
Russo I, et al "A short-term improvement of blood glucose control increases aspirin sensitivity in aspirin-resistant type 2 diabetic men" EASD 2012.