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Ticagrelor increases adenosine plasma concentration in patients with an acute coronary syndrome
Laurent Bonello1, Marc Laine2, Nathalie Kipson3
1Département de Cardiologie, Hôpital Universitaire Nord de Marseille, Assistance-Publique Hôpitaux de Marseille, Marseille, France; INSERM UMRS 1076, Aix-Marseille University, Marseille, France.
Insights
Ticagrelor significantly increases adenosine plasma concentration (APC) in acute coronary syndrome (ACS) patients by inhibiting adenosine uptake in red blood cells, unlike clopidogrel.
Area of Science:
- Pharmacology
- Cardiology
- Biochemistry
Background:
- Ticagrelor, a P2Y12 receptor antagonist, shows clinical benefits in ACS patients beyond platelet inhibition.
- Its non-platelet effects may involve interactions with adenosine metabolism, as suggested by preclinical studies.
Purpose of the Study:
- To investigate the effect of ticagrelor on adenosine plasma concentration (APC) in patients with acute coronary syndrome (ACS).
- To explore the mechanisms underlying ticagrelor-induced changes in APC.
Main Methods:
- Prospective randomization of 60 ACS patients to ticagrelor or clopidogrel.
- Measurement of APC using liquid chromatography.
- Assessment of adenosine deaminase activity, red blood cell adenosine uptake, and cyclic adenosine monophosphate production.
Main Results:
- Ticagrelor treatment resulted in significantly higher APC compared to clopidogrel (p < 0.01).
- Ticagrelor inhibited adenosine uptake by red blood cells, while adenosine deaminase activity and direct effects on adenosine receptors remained unchanged.
- APC levels did not correlate with P2Y12 receptor blockade.
Conclusions:
- Ticagrelor increases APC in ACS patients compared to clopidogrel.
- This increase is primarily mediated by the inhibition of adenosine uptake by red blood cells.
Objectives:
This study aimed to investigate the impact of ticagrelor on adenosine plasma concentration (APC) in acute coronary syndrome (ACS) patients.
Background:
Ticagrelor is a direct-acting P2Y12-adenosine diphosphate receptor blocker. The clinical benefit of ticagrelor compared with clopidogrel in ACS patients suggests that the drug has non-platelet-directed properties. Animal and in vitro models suggested that the "pleiotropic" properties of ticagrelor may be related to an interaction with adenosine metabolism.
Methods:
We prospectively randomized 60 ACS patients to receive ticagrelor or clopidogrel. The APC was measured by liquid chromatography. To assess the mechanism of APC variation, we measured adenosine deaminase concentration, adenosine uptake by red blood cells, and cyclic adenosine monophosphate production by cells overexpressing adenosine receptors. The P2Y12-adenosine diphosphate receptor blockade was assessed by the vasodilator-stimulated phosphoprotein index.
Results:
Patients receiving ticagrelor had significantly higher APC than patients receiving clopidogrel (1.5 μM [interquartile range: 0.98 to 1.7 μM] vs. 0.68 μM [interquartile range: 0.49 to 0.78 μM]; p < 0.01). The APC was not correlated with vasodilator-stimulated phosphoprotein (p = 0.16). Serum-containing ticagrelor inhibited adenosine uptake by red blood cells compared with clopidogrel or controls (p < 0.01 for both comparisons). Adenosine deaminase activity was similar in serum of patients receiving clopidogrel or ticagrelor (p = 0.1). Ticagrelor and clopidogrel had no direct impact on adenosine receptors (p = not significant).
Conclusions:
Ticagrelor increases APC in ACS patients compared with clopidogrel by inhibiting adenosine uptake by red blood cells.
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