Ticagrelor monotherapy following percutaneous coronary intervention for acute coronary syndrome in TWILIGHT patients: still a future for aspirin?

This commentary refers to ‘Ticagrelor alone vs. ticagrelor plus aspirin following percutaneous coronary intervention in patients with non-ST-segment elevation acute coronary syndromes: TWILIGHT-ACS’, by U. Baber et al., https://doi.org/10.1093/eurheartj/ehaa670 and the discussion piece ‘Aspirin-free strategies: a framework to reassess the role of dual antiplatelet therapy after percutaneous coronary intervention’, by D. Cao et al., https://doi.org/10.1093/eurheartj/ehab041. The present analysis corroborates the potential benefit of ticagrelor-monotherapy after a short double antiplatelet therapy (DAPT) in acute coronary syndrome (ACS) patients.1 The salient finding consists in the halving of the composite bleeding outcome in ACS patients (3.6% vs. 7.6%, P < 0.001), without negative impact on the composite ischaemic event (4.3% vs. 4.4%, P = 0.84). Some points warrant further discussion when combining previous similar observations with these data: Hitherto, the GLOBAL-LEADERS was the only study having proved the benefit of aspirin withdrawal at 1-month from the percutaneous coronary intervention (PCI), also in the acute setting including STEMI.2 Despite the high ischaemic burden, this strategy allowed to reduce by half the bleeding, without an increase of ischaemic complications. While the first 3 months exclusion in the present trial of patients sustaining BARC-3b or higher-grade bleeding, precludes any inference of DAPT effect within the first trimester, these data are available from the similar TICO trial, and clearly show how aspirin maintenance until ninety days is likely to increase bleeding events, presumably avoidable, even in the first 3 months.3 The hypothesis-generating evidence favouring 1-month DAPT, is furthermore sustained by in vitro studies, which would portend that despite its inhibitory activity on arachidonic acid-induced platelet aggregation, aspirin seems not to prevent platelets activation which follows their adherence to collagen reactive peptide at high-shear stress and hypoxic conditions, distinctive of ACS.4 Such hypothesis raises legitimate questions about the putative additive antithrombotic aspirin effect in preventing thrombosis induced by subendothelial collagen exposure, after unstable plaques treatment.4 Should DAPT be stopped earlier than 1 month or even never started?5 Furtherly, minimize bleeding risk sounds attractive, and counting on the latest generations stents advantages, dedicated trials could definitely prove it beyond doubt. The authors underlined the 3-fold higher prevalence of Asians among the ACS cohort, which could have influenced the magnitude of aspirin withdrawal benefits. This aspect deserves attention, especially in the high-risk TWILIGHT population and in this acute setting, well-known to even increase the bleeding risk. Although ethnicity is not included in the recent high-bleeding risk (HBR) criteria, the HBR-Academic Research Consortium consensus warned about its potential role on antithrombotic regimens choices. Indeed, several evidences suggest a differential ischaemia/bleeding trade-off in East-Asians vs. non-East-Asians, making the former more likely to incur in bleeding than ischaemic events, despite a higher level of platelet reactivity during DAPT (East-Asian paradox). Albeit the efficacy of lower P2Y12-doses in combination with aspirin has been already verified, specific aspirin-free regimens deserve investigation among this race.5 At present, it would be worthwhile to analyse how the ethnicity factor impacted the outcomes in the two treatment arms of this study. Such data, even if not derived from pre-specified analysis, would lay the foundation of future dedicated studies. The possibility of a low-dose P2Y12-monotherapy immediately after ACS-PCI in such a specific population might be not so unlikely.5 Concluding, while there is an increasing evidence towards a P2Y12-monotherapy after PCI, it is still unclear the best timing to stop aspirin and which populations, especially, would benefit more than others. Science Foundation Ireland Research Professorship Award (RSF 1413) including grant to M.L. Conflict of interest: P.W. Serruys reports personal fees from Biosensors, Micell Technologies, Sinomedical Sciences Technology, Philips/Volcano, Xeltis, Meril Life, Sahajanand Medical Technologies and HeartFlow, outside the submitted work. All other authors have no conflict of interest to declare.