Impact of a high-fat meal on assessment of clopidogrel-induced platelet inhibition in healthy subjects

Paul P Dobesh, Jamela F Urban, Scott W Shurmur, Julie H Oestreich, Paul P Dobesh, Jamela F Urban, Scott W Shurmur, Julie H Oestreich

Abstract

Background: Ideal conditions for platelet reactivity testing are critical for optimal selection of a P2Y12 inhibitor. Data are inconsistent regarding the impact of high-fat meals on test assessment.

Methods: Participants included 12 healthy subjects not taking antiplatelet drugs after a 12-hour fast. After baseline assessment, subjects were given a 600 mg dose of clopidogrel. Four hours later, maximum platelet inhibition was tested in the fasting state by light transmission aggregometry (LTA), VerifyNow P2Y12, vasodilator-stimulated phosphoprotein (VASP), and whole blood aggregometry (WBA). Subjects were then provided a high-fat meal, and platelet function was evaluated two hours later. Change in measured platelet aggregation by LTA was the primary endpoint of the study. The Wilcoxon Rank Sum test was used to compare the change in platelet reactivity between fasting and non-fasting conditions. The Spearman rho (ρ) correlation coefficient was used to evaluate the association between fasting platelet reactivity and the change following a high-fat meal.

Results: No significant change occurred in maximal light transmission, as assessed by LTA with 5 μM ADP (p = 0.15) and with 20 μM ADP (p = 0.07). There was a significant change in the area under the curve with 5 μM ADP (p = 0.03) but not with 20 μM ADP (p = 0.18). Although there was no significant change with the VerifyNow P2Y12 assay (p = 0.16), the change was correlated with the initial fasting value (Spearman's rho p = 0.008). The VASP assay and WBA varied minimally.

Conclusion: The high-fat meal did not significantly alter platelet function assessment of commonly used platelet function tests. Greater intra-subject variability existed for the optically-dependent compared with non-optically dependent tests.

Trial registration: NCT01307657.

Keywords: Blood platelets; Clopidogrel; Diet; High-fat; P2Y12 purinoceptor antagonist; Platelet function tests.

Figures

Figure 1
Figure 1
Study design.
Figure 2
Figure 2
Effect of a high-fat meal on the VASP P2Y12 assay. The change in platelet reactivity index from the on-treatment fasting to non-fasting state was not significantly different from zero (p = 0.35). n = 12.
Figure 3
Figure 3
Impact of a high-fat meal on ADP-stimulated light transmittance aggregometry. The change in maximal platelet aggregation on-clopidogrel from the fasting state compared to following the high-fat meal was not significantly different from zero for both concentrations of ADP, 5 μM (p = 0.15) and 20 μM (p = 0.068). n = 12.
Figure 4
Figure 4
Impact of a high-fat meal on the VerifyNow P2Y12 assay. The change in P2Y12 Reaction Units (PRU) was not significantly different from zero (p = 0.18). n = 12.
Figure 5
Figure 5
Correlation between fasting on-clopidogrel platelet reactivity and the change in on-treatment platelet reactivity after a high-fat meal for the VerifyNow P2Y12 assay. Spearman correlation coefficients (ρ) were generated for each assay to assess the correlation between: 1) fasting on-clopidogrel platelet reactivity and 2) the change in platelet reactivity on-clopidogrel from the fasting to the non-fasting state. The significant finding for the VerifyNow P2Y12 assay (p = 0.008) suggests that subjects with high platelet reactivity on clopidogrel may be selectively impacted by the high-fat meal, while subjects with a normal clopidogrel response may have more consistent results regardless whether or not a high-fat meal is taken.

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