ticagrelor and Hyperuricemia

During its development, ticagrelor, a drug designed to prevent thrombotic events in patients with acute coronary syndromes, was found to have an association with mild hyperuricemia. To investigate this effect further, we carried out a placebo-controlled, randomized, crossover study in 24 healthy male volunteers. The volunteers received ticagrelor (90 mg b.i.d. for 5 days), and serum uric acid and urinary uric acid excretion were assessed under strictly controlled conditions. After administration of ticagrelor, serum uric acid significantly increased (day 1: 4-6%; day 5: 4-10%) relative to placebo and rapidly returned to baseline after the last dose of the drug. Urinary uric acid excretion was significantly higher on day 1 (7%) and at 24-48 h after the morning dose on day 5 (17%) relative to placebo. Uric acid clearance was significantly higher 24-48 h after the morning dose on day 5 (11%). Uric acid fractional excretion was unaffected. Serum hypoxanthine and xanthine were elevated after multiple ticagrelor doses. No uric acid-related adverse events were seen. The study showed that ticagrelor-associated hyperuricemia is modest and reversible; serum uric acid elevation may have been caused by altered tubular secretion and/or increase in production.

Topics: Adenosine; Adult; Cross-Over Studies; Humans; Hyperuricemia; Hypoxanthine; Male; Middle Aged; Purinergic P2Y Receptor Antagonists; Ticagrelor; Time Factors; Uric Acid; Xanthine

Hyperuricemia carries an increased risk of atherothrombotic events in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). This may at least in part be due to inadequate P2Y12 inhibition. The aim of this study was to prospectively investigate the potential association between hyperuricemia and decreased platelet inhibition by P2Y12 antagonists.. Levels of uric acid as well as on-treatment residual platelet reactivity in response to adenosine diphosphate (ADP) were assessed in 301 clopidogrel-treated patients undergoing elective angioplasty and stenting, and in 206 prasugrel- (n = 118) or ticagrelor-treated (n = 88) ACS patients following acute PCI. Cut-off values for high on-treatment residual ADP-inducible platelet reactivity (HRPR) were based on previous studies showing an association of test results with clinical outcomes.. Hyperuricemia was significantly associated with increased on-treatment residual ADP-inducible platelet reactivity in clopidogrel- and prasugrel-treated patients in univariate analyses and after adjustment for differences in patient characteristics by multivariate regression analyses. In contrast, ticagrelor-treated patients without and with hyperuricemia showed similar levels of on-treatment residual platelet reactivity to ADP. HRPR occurred more frequently in clopidogrel- and prasugrel-treated patients with hyperuricemia than in those with normal uric acid levels. In contrast, hyperuricemic patients receiving ticagrelor did not have a higher risk of HRPR compared with those with normal uric acid levels.. Hyperuricemia is associated with decreased platelet inhibition by thienopyridines but a normal response to ticagrelor. It remains to be established if lowering uric acid increases the antiplatelet effects of clopidogrel and prasugrel in hyperuricemic patients with HRPR.

Topics: Acute Coronary Syndrome; Adenosine Diphosphate; Aged; Angioplasty; Clopidogrel; Comorbidity; Cytochrome P-450 CYP2C9; Female; Genotype; Humans; Hyperuricemia; Male; Middle Aged; Platelet Activation; Platelet Aggregation Inhibitors; Prospective Studies; Purinergic P2Y Receptor Antagonists; Stents; Thienopyridines; Ticagrelor; Ticlopidine; Uric Acid