Ticagrelor and central sleep apnoea: Impact of withdrawal and reintroduction

Abstract

These are both convincing case reports that emphasise the need for clinicians to be aware of this side effect of ticagrelor and search for central apnoeas in patients complaining from dyspnoea and fatigue during treatment. | Nomenclature of targets and ligandsKey protein targets and ligands in this article are hyperlinked to corresponding entries in http://www.guidetopharmacology.org, 10 the common portal for data from the IUPHAR/BPS Guide to PHARMACOLOGY.

Treating Central Sleep Apnea with One Modification

“…Previous case reports described emerging CSA with fatigue and witnessed apneas, which disappeared after stopping ticagrelor. A causal relationship was suggested by Puel and colleagues and Paboeuf and colleagues (6,7). They described patients who developed CSA on ticagrelor with normalization after interruption of ticagrelor.…”

Central Sleep Apnea in Patients With Coronary Heart Disease Taking P2Y12 Inhibitors

“…Prior studies have noted an association between ticagrelor use and CSA and a reversible conversion from OSA phenotype to CSA phenotype after the initiation of ticagrelor. 7 However, the reversibility of this phenomenon has only been demonstrated in case reports, and this relationship remains unclear. 7,8 One proposed mechanism of this change is through direct inhibition of P2Y12 receptors in the central nervous system and/or increased purinergic stimulation of the central nervous system and chemoreflex system due to elevated tissue concentrations of adenosine relative to that seen in clopidogrel or prasugrel use.…”

“…7 However, the reversibility of this phenomenon has only been demonstrated in case reports, and this relationship remains unclear. 7,8 One proposed mechanism of this change is through direct inhibition of P2Y12 receptors in the central nervous system and/or increased purinergic stimulation of the central nervous system and chemoreflex system due to elevated tissue concentrations of adenosine relative to that seen in clopidogrel or prasugrel use. [22][23][24] Another proposed mechanism suggests that ticagrelor's effects on pulmonary C fibers either through its inhibition of the type 1 equilibrative nucleoside transporter protein (ENT1) and its effects on tissue adenosine levels or directly through P2Y12 receptors on pulmonary C fibers, which may be the driver for the Cheyne-Stokes respiration present in CSA.…”

“…5 There have been case reports and a small prospective study that have suggested an association between the initiation of the P2Y12 inhibitor, specifically ticagrelor, and CSA incidence. [6][7][8][9] However, there is conflicting data from a larger registry analysis that refutes any relationship between ticagrelor and CSA. 10 As ticagrelor has become more widely used given its benefits over other P2Y12 inhibitors in patients with acute coronary syndrome (ACS) and by extension in patients with CHD, it is important that such a relationship be clarified.…”