Recovery of platelet reactivity following cessation of either aspirin or ticagrelor in patients treated with dual antiplatelet therapy following percutaneous coronary intervention: a GLOBAL LEADERS substudy

Abstract

Cessation of one component of dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) has been associated with increased risk of ischemic events but it is uncertain whether discontinuation of aspirin is preferable to discontinuation of the oral P2Y₁₂ inhibitor. The GLOBAL LEADERS study compared two antiplatelet strategies following PCI, cessation of aspirin at 1 month with continued ticagrelor monotherapy for 23 months versus standard DAPT for 12 months followed by aspirin monotherapy for a further 12 months. We assessed recovery of platelet reactivity after withdrawal of either aspirin or ticagrelor at 1 month and 12 months, respectively, in this study. Platelet aggregation (PA) was assessed before cessation of DAPT (‘baseline’) and after 2, 7, and 14 days post-cessation using Multiplate whole-blood aggregometry with collagen, thrombin-receptor-activating peptide (TRAP), adenosine diphosphate (ADP) and arachidonic acid (AA) as agonists. Following cessation of aspirin at 1 month, there was marked recovery of PA induced by AA (baseline [mean ± SD]: 11.1 ± 7.4 U vs. 14 days: 64.9 ± 19.6 U, p < .0001) and collagen (37.4 ± 22.9 U vs. 79.8 ± 13.8 U, p < .0001), whereas PA induced by ADP (18.6 ± 6.6 vs. 69.1 ± 20.5, p < .0001) and collagen (34.4 ± 18.7 U vs. 43.0 ± 21.0, p = .0018) recovered following cessation of ticagrelor at 12 months. There were no significant changes in TRAP-induced PA in either group. In conclusion, cessation of either component of DAPT leads to substantial increase in platelet reactivity with differential effects on different pathways of platelet activation when aspirin or the P2Y₁₂ inhibitor is stopped. Further work is required to determine which patients receive net benefit from long-term continuation of DAPT.

Keywords:

• Aspirin
• percutaneous coronary intervention
• platelet aggregation
• ticagrelor

Author roles

Conceived, designed and set up the study: B. W. Hennigan, R. Good, K. G. Oldroyd, L. Anderson, M. Campbell. Data collection and analysis: B. W. Hennigan, L. Martin, C. Adamson, W.A.E. Parker. Wrote the paper: B. W. Hennigan, R. Good, C. Adamson, W.A.E. Parker, R.F. Storey, K. G. Oldroyd.

Declaration of Interest

B. W. Hennigan, R. Good, C. Adamson, L. Martin, L. Anderson, M. Campbell, and W.A.E. Parker declare no conflicts of interest. R.F. Storey reports institutional research grants/support from AstraZeneca, GlyCardial Diagnostics and Thromboserin; consultancy fees from Amgen, AstraZeneca, Bayer, Bristol Myers Squibb/Pfizer, Cytosorbents, GlyCardial Diagnostics, Haemonetics, HengRui, Portola, Sanofi Aventis and Thromboserin; and honoraria from AstraZeneca, Bayer, Bristol Myers Squibb/Pfizer, Intas Pharmaceuticals and Medscape. K. G. Oldroyd is Chief Medical Officer of Biosensors International, which provided funding for the GLOBAL LEADERS study.

Additional information

Funding

This work was supported by British Heart Foundation Project Grant PG/14/97/31263 and AstraZeneca UK Limited. Dr. William Parker is supported by the British Heart Foundation Clinical Research Training Fellowship no. FS/18/49/33752.