22E Impact of a High-Fat Meal on Assessment of Clopidogrel-Induced Platelet Inhibition in Healthy Subjects

Wednesday, October 24, 2012
Westin Diplomat Resort
Paul P. Dobesh, Pharm.D.1, Jamela Urban, Pharm.D.2, Scott Shurmur, MD2 and Julie H. Oestreich, PharmD, PhD3
1University of Nebraska Medical Center, Omaha, NE
2The Nebraska Medical Center, Omaha, NE
3Department of Pharmacy Practice, University of Nebraska Medical Center, Omaha, NE

Purpose: We conducted this study to evaluate whether a high-fat meal impacts the ability of various platelet function tests to assess platelet reactivity for patients on clopidogrel.

Methods: Healthy subjects not taking antiplatelet drugs presented after a 12 hour fast. After baseline platelet function assessment, subjects were given a 600 mg dose of clopidogrel. Four hours after the dose, maximum platelet inhibition was tested in the fasting state. Subjects were then provided a standardized high-fat meal, and platelet function was evaluated 2 hours later. Platelet function was assessed by 2 optically dependent assays (LTA and VerifyNow P2Y12) and 2 non-optically dependent assays [vasodilator-stimulated phosphoprotein (VASP) and whole blood aggregometry (WBA)]. Platelet function was compared before and after the high-fat meal with the Wilcoxon matched-pair signed-rank test.

Results: Twelve healthy adults were recruited.  The mean triglyceride level increased following the high-fat meal (79 mg/dL vs. 132 mg/dL; p=0.002). There was no significant change in maximal light transmission as assessed by LTA (range -9% to 11% with 5µM ADP; p=0.15 and -9% to 10% with 20µM ADP; p=0.07). There was a significant change in the area under the curve with 5µM ADP (range -9 to 65; p=0.03) but not with 20µM ADP (range -41 to 63; p=0.18). Although there was no significant change in P2Y12 Reaction Units with the VerifyNow P2Y12 assay (range -28 to 47; p=0.16), the change was correlated with the initial fasting value (Spearman’s rho p=0.01). There was minimal variability with the VASP assay (range -4.4 to 5.4; p=0.35), and no changes were evident with WBA.

Conclusion: The intake of a high-fat meal did not significantly alter platelet function assessment of commonly used platelet function tests. There was more intra-subject variability with the optically dependent compared with non-optically dependent platelet function tests.