The Effect of Aspirin Dosing on Platelet Function in Diabetic and Nondiabetic Patients

Abstract

OBJECTIVE-Diabetic patients may have a higher prevalence of platelet aspirin resistance than nondiabetic patients. Our goal was to analyze platelet aspirin responsiveness to various aspirin doses in diabetic and nondiabetic patients. RESEARCH DESIGN AND METHODS-We examined the effect of aspirin (81, 162, and 325 mg/day for 4 weeks each) on platelet aspirin responsiveness in 120 stable outpatients (30 diabetic patients and 90 nondiabetic patients) with coronary artery disease (CAD) using light transmittance aggregometry (LTA), VerifyNow, platelet function analyzer (PFA)-100, and levels of urinary 11-dehydro-thromboxane B 2 (11-dh-TxB 2 ).RESULTS-In the total group, a low prevalence (0 -2%) of aspirin resistance was observed with all aspirin doses as determined by arachidonic acid-induced LTA. Aspirin resistance was higher at the 81-mg dose in diabetic versus nondiabetic patients using collagen-induced LTA (27 vs. 4%, P ϭ 0.001), VerifyNow (13 vs. 3%, P ϭ 0.05), and urinary 11-dh-TxB 2 (37 vs. 17%, P ϭ 0.03). Diabetic patients treated with 81 mg exhibited higher platelet function measured by VerifyNow, collagen-and ADP-induced LTA, and 11-dh-TxB 2 levels (P Յ 0.02 for all comparisons). Higher aspirin doses significantly inhibited platelet function and decreased aspirin resistance in diabetic patients (P Ͻ 0.05).CONCLUSIONS-Diabetic patients with CAD treated with 81 mg aspirin exhibit a higher prevalence of aspirin resistance and have significantly higher ADP-and collagen-induced platelet aggregation, 11-dh-TxB 2 levels, and aspirin reaction units measured by VerifyNow than nondiabetic patients. Increased aspirin dosing resulted in similar rates of resistance and platelet function levels between groups. These findings indicate that diabetic patients exhibit a global high platelet reactivity phenotype that may be partially overcome by higher aspirin doses. Diabetes 56: 3014-3019, 2007

Effect of Aspirin Dose on Mortality and Cardiovascular Events in People with Diabetes: A Meta-Analysis

“…This hypothesis, generated from pharmacologic evidence of a dose-response relationship between aspirin and antiplatelet activity in diabetic patients, 28 …”

“…[25][26][27] Although the exact mechanisms are not clear, a subgroup analysis of the Aspirin-Induced Platelet Effect (ASPECT) study demonstrated that diabetic patients exhibited a significantly lower rate of resistance when given >100 mg daily compared with a lower (and more commonly used) dose of 81 mg daily. 28,29 Moreover, Electronic supplementary material The online version of this article (doi:10.1007/s11606-011-1757-y) contains supplementary material, which is available to authorized users.…”

Wytyczne ESC dotyczące cukrzycy, stanu przedcukrzycowego i chorób układu sercowo- -naczyniowego opracowane we współpracy z EASD

“…Obecnie zaleca się podawanie tego leku w dawce 75-162 mg raz na dobę, to jest według takiego samego schematu dawkowania, jak u osób bez cukrzycy [263,264]. Jednak podawanie małej dawki kwasu salicylowego raz na dobę może nie zapewnić całkowitego hamowania aktywności płytkowej COX-1 i czynności płytek zależnej od tromboksanu A2 [265][266][267], co jest prawdopodobnie spowodowane zwiększonym obrotem płytek w cukrzycy [268]. Dane na ten temat wskazują, że u osób z cukrzycą i CVD stosowanie ASA 2 razy dziennie może przynieść korzystne efekty w postaci ciągłej skuteczności [268,269].…”

Diabetes and Aspirin Resistance

“…(ten Berg, Gerritsen et al 2002) Because patients with diabetes exhibit a higher prevalence of aspirin resistance on standard aspirin doses (81 mg/day) and have significantly higher ADP-and collagen-induced platelet aggregation, 11-dehydro-TxB 2 levels and the aspirin resistance may be partially overcome by higher aspirin doses. (DiChiara, Bliden et al 2007) Laboratory and genetic inconsistency, as well as dose dependence, is seen when agonists other than arachidonic acid (the most specific in assessing aspirin resistance), such as ADP, collagen, and epinephrine, are used for in vitro assessment of platelet inhibition by aspirin. (McCabe, Harrison et al 2005;Assadian, Lax et al 2007;Gurbel, Bliden et al 2007).…”