Differential impact of diabetes mellitus on antiplatelet effects of prasugrel and clopidogrel

Figures

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  Fig. 1. Study design at loading dose. Forty patients who were scheduled for percutaneous coronary intervention (PCI) under treatment with aspirin were randomized at admission to treatment of either a 20-mg loading dose (LD) of prasugrel or a 300-mg LD of clopidogrel. Platelet function analyses were performed at five time points (baseline, and 0.5, 3, 6, and 20 h) after the LD. Active metabolite concentrations were measured at 0.5 and 3 h after the LD

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  Fig. 2. Comparison of platelet function after the loading dose (LD) between clopidogrel and prasugrel. a The vasodilator-stimulated phosphoprotein-platelet reactivity index (VASP-PRI) was measured at the indicated time points after the LD. b, c Platelets in platelet-rich plasma obtained at the indicated time points were stimulated with 5 μM adenosine diphosphate (ADP) (b) or 20 μM ADP (c). The absolute change in maximal platelet aggregation as assessed by light transmission (baseline – an indicated point) was calculated. Blue lines and red lines represent the prasugrel LD (20 mg) and clopidogrel LD (300 mg), respectively. Values are means ± SEM. Differences in the time course between groups were determined by repeated measures ANOVA

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  Fig. 3. Changes in the correlation coefficient between variables. a Changes in Spearman’s correlation coefficient according to the time course between the vasodilator-stimulated phosphoprotein-platelet reactivity index (VASP-PRI) and active metabolite concentrations (AM) measured at 30 min after the LD. b Changes in Spearman’s correlation coefficient according to the time course between the VASP-PRI and maximal platelet aggregation induced by 20 μM adenosine diphosphate (ADP). Blue lines and red lines represent the LD of prasugrel (20 mg) and that of clopidogrel (300 mg), respectively. *P < 0.05; **P < 0.01; ***P < 0.001

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  Fig. 4. Platelet aggregation as assessed by the laser light scattering method after the loading dose (LD). Platelets in platelet-rich plasma obtained at the indicated time points after the LD were stimulated with 5 μM adenosine diphosphate (ADP) (a–c) or 20 μM ADP (d–f). Small (a, d), medium (b, e), and large (c, f) platelet aggregate formation was measured by the laser light scattering method. This formation is expressed as changes in the area under curve (AUC) of each platelet aggregate number during 5 min ( x 106 V/min). Blue lines and red lines represent the LD of prasugrel (20 mg) and that of clopidogrel (300 mg), respectively. Values are means ± SEM. Differences in the time course between groups were determined by repeated measures ANOVA

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  Fig. 5. Differential effect of diabetes on active metabolite formation and platelet function between prasugrel and clopidogrel. a, d Plasma active metabolite (AM) levels after the loading dose (LD) of prasugrel (a) or clopidogrel (d) were measured at 0.5 and 3 h after treatment in patients without diabetes (blue bar) and those with diabetes (red bar). Values are means ± SEM. Statistical significance was determined using the Mann–Whitney U test. b, e The vasodilator-stimulated phosphoprotein-platelet reactivity index (VASP-PRI) was measured at the indicated time points after the LD of prasugrel (b) or clopidogrel (e). Blue lines and red lines represent patients without diabetes and those with diabetes, respectively. Values are means ± SEM. Differences in the time course between groups were determined by repeated measures ANOVA. c, f Platelets in platelet-rich plasma obtained at the indicated time points were stimulated with 20 μM adenosine diphosphate (ADP). The absolute change in maximal platelet aggregation after the LD of prasugrel (c) or clopidogrel (f) as assessed by light transmission (base line – an indicated point) was calculated. Blue lines and red lines represent patients…