| Summary: | Platelets participate centrally in atherothrombosis, resulting in vessel
occlusion and ischaemia. Consequently, optimisation of antiplatelet regimens has
the potential to further reduce the residual burden of morbidity and mortality
associated with atherosclerosis. Ticagrelor is a potent oral platelet P2Y12
receptor antagonist that (1) inhibits a central amplification pathway of platelet
activation directly as well as via an active metabolite, (2) has a rapid onset
and offset of antiplatelet action that remains consistent in the circulation
during twice-daily administration and is amenable to reversal, (3) has inverse
agonist properties, and (4) demonstrates pleiotropic effects that contribute to
anti-thrombotic, anti-inflammatory and vasodilatory properties. These
advantageous characteristics of ticagrelor have translated to beneficial clinical
outcomes in patients with acute coronary syndromes or ischaemic stroke, during
prolonged maintenance therapy in specific high-risk populations, and following
percutaneous coronary intervention but not definitively following coronary artery
bypass graft surgery or in peripheral artery disease patients. Novel innovative
strategies aim to reduce the risk of bleeding during dual antiplatelet therapy
via shortening the duration of treatment and replacing the standard-of-care with
ticagrelor monotherapy. In cases where aspirin is an essential component in
secondary prevention, dose modification when combined with ticagrelor may
hypothetically provide desirable clinical outcomes following appropriate clinical
assessment as predicted by pharmacological studies. Overall, the future
management of acute coronary syndromes could potentially involve the
dichotomisation of antithrombotic therapies, whereby only those with high-risk of
ischaemia, without a high-risk of bleeding, receive ticagrelor plus very-low-dose
aspirin, while ticagrelor monotherapy is administered to the remaining majority.
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