Novel approaches to P2Y₁₂ inhibition and aspirin dosing

Abstract

Aspirin and P2Y₁₂ inhibitors remain commonly prescribed antiplatelet drugs in the treatment of atherothrombotic conditions. Despite established benefits of dual antiplatelet therapy (DAPT) in the setting of acute coronary syndromes, there remains residual ischemic risk in this group and the problem of bleeding complications is an ongoing issue. DAPT with aspirin and ticagrelor has now been studied in other patient groups such as those with concurrent diabetes and stable coronary artery disease, and those undergoing elective percutaneous coronary intervention (PCI). Recent trials of ticagrelor monotherapy have suggested this may have benefits over standard-of-care in some settings, such as PCI, but not in others such as peripheral arterial disease or stroke. A novel subcutaneously administered P2Y₁₂ inhibitor, selatogrel, has shown powerful, rapid and consistent effect in a phase 2 study. Aspirin dosing remains an area of investigation, particularly in the setting of DAPT. A novel regimen of very-low-dose twice-daily aspirin has hypothetical advantages in pharmacodynamic and pharmacokinetic effects, maintaining antiplatelet effect whilst reducing potentially harmful peak-trough variation.

Graphical Abstract

Keywords:

• Aspirin
• atherothrombosis
• P2Y12 inhibitors

Acknowledgements

W.A.E. Parker is funded by a British Heart Foundation Clinical Research Training Fellowship (FS/18/49/33752).

Declarations of Interest

R.F. Storey reports institutional research grants/support from AstraZeneca and GlyCardial Diagnostics; consultancy fees from Amgen, AstraZeneca, Bayer, Bristol Myers Squibb/Pfizer, GlyCardial Diagnostics, Haemonetics, Idorsia, Novartis, Portola and Thromboserin; and honoraria from AstraZeneca, Bayer, Bristol Myers Squibb/Pfizer and Medscape. W.A.E. Parker reports no relevant conflicts of interest.

Statement of Contributorship

W.A.E. Parker drafted the manuscript under the supervision of R.F. Storey, who edited and approved the final version.