Key result
Clopidogrel improves microcirculatory endothelial function by ~22 percentage points more in high platelet aggregation.
Why the study?
Does clopidogrel improve microcirculatory endothelial function in relatively healthy persons?
Does clopidogrel improve microcirculatory endothelial function in relatively healthy persons?
Absolute Event Rate: 39.4% vs 17.4%
p-value: p=0.03
Short-term clopidogrel administration improves microcirculatory endothelial function in healthy individuals with high baseline platelet aggregation, suggesting additional vascular benefits beyond platelet inhibition.
Clopidogrel-associated endothelial gains in healthy high-aggregation persons are hypothesis-generating; leaves open clinical relevance for cardiovascular outcomes.
BACKGROUND: Platelet activation can lead to enhanced oxidative stress, inflammatory response, and endothelial dysfunction. To quantify the effects of platelet inhibition on endothelial function, we assessed platelet activity of healthy persons before and after clopidogrel administration and evaluated its effects on endothelial function. We hypothesized that clopidogrel, by attenuating platelet activity, would result in enhanced endothelial function. METHODS AND RESULTS: Microcirculatory endothelial function was quantified by laser Doppler flowmetry (LDF) mediated by thermal hyperemia (TH) and postocclusive reactive hyperemia, respectively, in 287 and 241 relatively healthy and homogenous Old Order Amish persons. LDF and platelet aggregation measures were obtained at baseline and after 7 days of clopidogrel administration. Our primary outcome was percentage change in post- versus preclopidogrel LDF measures. Preclopidogrel TH-LDF and platelet aggregation were higher in women than in men (P<0.001). Clopidogrel administration was associated with ≈2-fold higher percentage change in TH-LDF in participants with high versus low baseline platelet aggregation (39.4±10.1% versus 17.4±5.6%, P=0.03). Clopidogrel also increased absolute TH-LDF measures in persons with high platelet aggregation (1757±766 to 2154±1055, P=0.03), with a more prominent effect in women (1909±846 to 2518±1048, P=0.001). There was no evidence that clopidogrel influenced postocclusive reactive hyperemia LDF measures. CONCLUSIONS: The administration of clopidogrel in healthy persons with high baseline platelet aggregation results in improved TH-induced microcirculatory endothelial function. These data suggest that clopidogrel may have a beneficial effect on microcirculatory endothelial function, presumably through antiplatelet activity, and may confer additional vascular benefits. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00799396.
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Salimi et al. (2016) studied Healthy (assessed for heightened platelet aggregation) (n=287). Clopidogrel vs. Low baseline platelet aggregation group (or pre-clopidogrel baseline) was evaluated on Percentage change in post- versus preclopidogrel thermal hyperemia laser Doppler flowmetry (TH-LDF) (p=0.03). Clopidogrel administration resulted in a significantly higher percentage increase in thermal hyperemia-induced microcirculatory endothelial function among healthy persons with high baseline platelet aggregation compared to those with low aggregation (39.4% vs 17.4%, P=0.03).
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