Platelet reactivity and coronary microvascular impairment after percutaneous revascularization in stable patients receiving clopidogrel or prasugrel

Mangiacapra, Fabio; Pellicano, Mariano; Serafino, Luigi Di; Bressi, Edoardo; Peace, Aaron; Gioia, Giuseppe Di; Morisco, Carmine; Bartúnek, Jozef; Wijns, William; Bruyne, Bernard De; Barbato, Emanuele

doi:10.1016/j.atherosclerosis.2018.08.044

Cited by 18 publications

(17 citation statements)

References 22 publications

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“…In this study, after logistic regression analysis with extrinsic and intrinsic variables in the total population and the subgroup with dyslipidemia, we discovered that the quantity of stent was correlated with CR, which was similar to the findings in our former research . This finding might be due to coronary microvascular impairment in patients after (PCI), which would increase the platelet reactivity . Moreover, we found that liver function and albumin levels would affect the clopidogrel response.…”

Section: Discussionsupporting

confidence: 88%

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Association of PON1 gene promoter DNA methylation with the risk of Clopidogrel resistance in patients with coronary artery disease

et al. 2019

Clinical Laboratory Analysis

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Background and AimsThe failure of therapeutic response to clopidogrel in platelet inhibition, which is called clopidogrel resistance (CR), is more likely to cause cardiovascular events. We aimed to study the contribution of promoter DNA methylation of paraoxonase 1 (PON1) to the risk of clopidogrel poor response.MethodsThrough VerifyNow P2Y12 assay, patient’ platelet functions were measured. Among 57 non‐CR and 49 CR patients, the levels of DNA methylation in four CpG dinucleotides on the PON1 promoter were tested using bisulfite pyrosequencing technology. Besides, the relative expression of PON1 mRNA was analyzed by quantitative real‐time PCR. Logistic regression was applied to investigate the interaction of PON1 methylation and clinical factors in CR.ResultsIn the subgroup with dyslipidemia, we discovered that higher CpG4 levels of the PON1 promoter indicated a poorer clopidogrel response (cases versus controls (%): 51.500 ± 14.742 vs 43.308 ± 10.891, P = 0.036), and the PON1 mRNA expression was reduced in CR patients. Additionally, the logistic regression indicated that higher level of albumin and the index of ALT were related to a lower risk of CR, and the index of AST as well as the quantity of stent may be positively associated with CR.ConclusionsThe DNA methylation of CpG4 in the PON1 promoter would lead to a low expression of PON1 mRNA, which might induce clopidogrel resistance in the patients with dyslipidemia, and the number of stents might be a risk for CR.

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Section: Discussionsupporting

confidence: 88%

“…19 This finding might be due to coronary microvascular impairment in patients after (PCI), which would increase the platelet reactivity. 23 Moreover, we found that liver function and albumin levels would…”

Section: Discussionmentioning

confidence: 90%

Association of PON1 gene promoter DNA methylation with the risk of Clopidogrel resistance in patients with coronary artery disease

et al. 2019

Clinical Laboratory Analysis

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“…As a consequence, the hypothesis that an enhanced antiplatelet effect with a different P2Y12 inhibitor could exert a protective effect on the microcirculation during elective PCI has been explored in the ProMicro 2 trial [ 81 ]: notably, we demonstrated that, compared with clopidogrel, a single loading dose of prasugrel was able to prevent microvascular impairment and ischemic complications in the setting of elective PCI. Furthermore, a significant correlation was found between the IMR and platelet reactivity, thus confirming that the protective effect of prasugrel on coronary microcirculation is mainly attributable to the attenuation of the PCI-related increase in the platelet reactivity [ 82 ].…”

Section: Clinical Utility Of Microvascular Function Assessment and Future Perspectivesmentioning

confidence: 80%

Invasive Assessment of Coronary Microvascular Function

Mangiacapra

Viscusi

Verolino

et al. 2021

JCM

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The critical role of the coronary microvascular compartment and its invasive functional assessment has become apparent in light of the significant proportion of patients presenting signs and symptoms of myocardial ischemia, despite the absence of epicardial disease, or after the adequate treatment of it. However, coronary microvascular dysfunction (CMD) represents a diagnostic challenge because of the small dimensions of the coronary microvasculature, which prevents direct angiographic visualization. Several diagnostic tools are now available for the invasive assessment of the coronary microvascular function, which, in association with the physiological indices used to investigate the epicardial department, may provide a comprehensive evaluation of the coronary circulation as a whole. Recent evidence suggests that the physiology-guided management of CMD, although apparently costly and time-consuming, may offer a net clinical benefit in terms of symptom improvement among patients with angina and ischemic heart disease. However, despite the results of several observational studies, the prognostic effect of the physiology-driven management of CMD within this population is currently a matter of debate, and therefore represents an unmet clinical need that urgently deserves further investigation.

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“…In the Protecting Microcirculation During Coronary Angioplasty (PROMICRO)-2 Randomized Study ( 6 ), the microvascular impairment induced by coronary stenting was reduced following antiplatelet therapy with prasugrel. As well, a linear correlation between platelet inhibition and PCI-induced coronary microvascular impairment could be shown ( 7 ). Given its more potent antiplatelet effect, prasugrel was associated with significantly lower microvascular resistances ( 7 ), which might in turn result in better myocardial perfusion.…”

Section: Introductionmentioning

confidence: 95%

“…As well, a linear correlation between platelet inhibition and PCI-induced coronary microvascular impairment could be shown ( 7 ). Given its more potent antiplatelet effect, prasugrel was associated with significantly lower microvascular resistances ( 7 ), which might in turn result in better myocardial perfusion. In another paper, no difference was shown between prasugrel and ticagrelor in preventing coronary microvascular injury following a ST-elevation myocardial infarction ( 8 ).…”

Section: Introductionmentioning

confidence: 95%

Effects of Clopidogrel, Prasugrel and Ticagrelor on Microvascular Function and Platelet Reactivity in Patients With Acute Coronary Syndrome Undergoing Coronary Artery Stenting. A Randomized, Blinded, Parallel Group Trial

Schnorbus

Jurk

Lackner

et al. 2021

Front. Cardiovasc. Med.

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Aims: In this pre-specified analysis of the “endothelium, stent and antiplatelet therapy” study, we investigate the impact of antiplatelet therapies on microvascular function in patients undergoing stenting for an acute coronary syndrome.Methods and Results: Fifty-six patients [age: 63(55–67) years, males, 10 diabetics, 27 non-ST-elevation myocardial infarction] were randomized to receive clopidogrel, ticagrelor or prasugrel in form of oral loading 2 h before stenting followed by oral therapy. Investigators were blinded to the allocation. Laser-Doppler microvascular function and ADP-induced platelet aggregation capacity were measured at baseline, 2 h after oral antiplatelet loading, and 1 day, 1 week and 1 month after stenting during chronic therapy with the same antiplatelet agent. Platelet aggregation decreased in all groups 2 h after oral loading, with a significantly larger effect in the prasugrel group (P = 0.009). Similarly, prasugrel and ticagrelor loading was followed by an increase in microvascular reactive hyperemia (P = 0.007 and P = 0.042 compared to clopidogrel). This effect disappeared one day after coronary intervention, with a significant decrease in the prasugrel group (P = 0.026). Similarly, analysis of microvascular conductance showed a larger increase in the prasugrel group 2 h after loading (P = 0.022 among groups), and a decrease in all groups after stenting.Conclusions: Oral loading with prasugrel (and less consistently ticagrelor) is associated with improved microvascular function and stronger platelet inhibition in acute coronary syndrome patients. The microvascular effect was however lost 1 day after stenting and during subsequent follow-up. Further studies are necessary to clarify the the long-term effects and potential benefits of P2Y12 inhibitors on microvascular damage.ClINICALTRIALS.gov N°: NCT01700322EUDRACT-N°: 2011-005305-73.

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Platelet reactivity and coronary microvascular impairment after percutaneous revascularization in stable patients receiving clopidogrel or prasugrel

Cited by 18 publications

References 22 publications

Association of PON1 gene promoter DNA methylation with the risk of Clopidogrel resistance in patients with coronary artery disease

Association of PON1 gene promoter DNA methylation with the risk of Clopidogrel resistance in patients with coronary artery disease

Invasive Assessment of Coronary Microvascular Function

Effects of Clopidogrel, Prasugrel and Ticagrelor on Microvascular Function and Platelet Reactivity in Patients With Acute Coronary Syndrome Undergoing Coronary Artery Stenting. A Randomized, Blinded, Parallel Group Trial

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