Effect of ASA dose doubling versus switching to clopidogrel on plasma inflammatory markers concentration in patients with type 2 diabetes and high platelet reactivity: the AVOCADO study.
BACKGROUND
The aim of the study was to compare the effects of 2 strategies of antiplatelet treatment (i.e., 150 mg ASA vs. 75 mg clpoidogrel) on plasma level of inflammatory markers in type 2 diabetes mellitus (T2DM) patients with high platelet reactivity (HPR).


METHODS
Study cohort consisted of 304 T2DM patients on chronic ASA therapy (75 mg per day) participating in the Aspirin Versus/Or Clopidogrel in Aspirin-resistant Diabetics inflammation Outcomes (AVOCADO) study. Patients with HPR defined as Platelet Function Analyzer (PFA)-100 collagene/epinephrine closure time (CEPI-CT) < 193 s (n = 80) were randomized to 150 mg of ASA or 75 mg of clopidogrel in 2:3 ratio, respectively. Concentrations of the selected inflammatory markers, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, solubleCD40 ligand (sCD40L), and high sensitivity C-reactive protein (hsCRP), were measured and compared in both treatment groups before and after 8 weeks of treatment in both groups.


RESULTS
Out of 234 patients included into final analysis, the total of 34.2% (n = 80) patients displayed HPR, of which 14.1% (n = 33) were randomized into 150 mg of ASA group and 20.1% (n = 47) into 75 mg of clopidogrel group. Treatment with clopidogrel was a positive predictor (stepwise multiple regression analysis) of reduction of sCD40L concentration (odds ratio [OR] 4.15; p = 0.013), while treatment with 150 mg ASA was a positive predictor of reduction of IL-6 concentration (OR 4.38; p = 0.033). There was no statistically significant differences between clopidogrel and ASA 150 mg treatment in respect to predictive value for decreased hsCRP concentrations or increased TNF-α concentrations.


CONCLUSIONS
Increasing the dose of ASA from 75 mg to 150 mg daily or switching ASA 75 mg to clopidogrel 75 mg daily may reduce concentrations of some inflammatory markers (in particular hsCRP, IL-6 and CD40L) in T2DM patients with HPR treated previously with 75 mg of ASA.
Department of Cardiology, Medical University of Warsaw, Poland. mpostula@wum.edu.pl.
Marek
M
Rosiak
Marek
M
Postula
Agnieszka
A
Kaplon-Cieslicka
Agnieszka
A
Kondracka
Ewa
E
Trzepla
Andrzej
A
Czlonkowski
Piotr K
PK
Janicki
Krzysztof J
KJ
Filipiak
Grzegorz
G
Opolski
D001241:Aspirin / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D023201:CD40 Ligand / Q000097:blood; D016009:Chi-Square Distribution; D000077144:Clopidogrel; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D057915:Drug Substitution; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D016015:Logistic Models; D015999:Multivariate Analysis; D016017:Odds Ratio; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D010979:Platelet Function Tests; D011044:Poland; D011446:Prospective Studies; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D015415:Biomarkers; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D010975:Platelet Aggregation Inhibitors; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D002097:C-Reactive Protein; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin