Dropping aspirin shortly after percutaneous coronary intervention (PCI) is associated with lower bleeding and mortality risks, without a concomitant increase in cardiovascular ischaemic recurrences compared with standard dual antiplatelet therapy (DAPT) continuation, a meta-analysis published in JACC: Cardiovascular Interventions has concluded.
The analysis was authored by Marco Valgimigli (Cardiocentro Ticino Institue, Ente Ospedaliero Cantonale, Lugano and Department of Cardiology, Bern University Hospital, Bern, Switzerland) et al, and sought to compare the use of ticagrelor monotherapy to DAPT—the current standard of care post-PCI.
Patients undergoing a dual course of antiplatelet therapy are given aspirin and an oral P2Y12 inhibitor after PCI to reduce the risk of ischaemic events, but its prolonged use can create a heightened risk of major bleeding, mortality and morbidity.
Valgimigli and colleagues note that an emerging bleeding reduction strategy has been to discontinue aspirin and maintain patients on P2Y12 inhibitor monotherapy. However, they note that data are still limited on this strategy, and the interpretation of available evidence is challenged by variations in patient selection, choice of P2Y12 inhibitor, duration of the initial DAPT regimen, timing of randomisation, and endpoint ascertainment. To address this, the study team carried out a systematic review and individual patient data (IPD) analysis of randomised trials to compare the safety and efficacy of ticagrelor monotherapy with standard DAPT.
Two randomised trials met the inclusion criteria—GLASSY (a sub-study of the GLOBAL LEADERS trial) and TWILIGHT—including a total of 14,628 patients undergoing PCI. Primary outcomes included the composite of Bleeding Academic Research Consortium type 3 or 5 bleeding tested for superiority and, if met, the composite of all-cause death, myocardial infarction, or stroke at one year, tested for noninferiority against a margin of 1.25 on a hazard ratio (HR) scale.
Analysing the findings of the two randomised trials, Valgimigli et al report that BARC type 3 or 5 bleeding occurred in fewer patients with ticagrelor than DAPT (0.9% vs. 1.7%, respectively), while the composite of all-cause death, myocardial infarction, or stroke occurred in 231 patients (3.2%) with ticagrelor and in 254 patients (3.5%) with DAPT. Ticagrelor was associated with lower risk for all-cause and cardiovascular mortality. Rates of myocardial infarction (2.01% vs. 2.05%), stent thrombosis (0.29% vs. 0.38%), and stroke (0.47% vs. 0.36%) were similar.
Discussing these findings, Valgimigli et al write that the analysis provides “strong evidence” that ticagrelor monotherapy, after a short course of one- or three-month DAPT, was associated with a lower risk for major bleeding without any measurable increase in ischaemic events compared with standard DAPT.
The study’s authors also observed a significant reduction in all-cause mortality among patients randomised to ticagrelor monotherapy, driven mostly by a reduction of cardiovascular death, but point out that this “requires a cautious interpretation” in view of the similar rates of myocardial infarction, stent thrombosis and stroke.
In conclusion, the authors write: “Compared with conventional DAPT, ticagrelor monotherapy was associated with a lower risk for major bleeding without evidence of a trade-off in terms of an increase in ischaemic risk among patients who underwent drug-eluting stent implantation. The observed benefit in terms of mortality needs further investigation.”
“The reduction of bleeding events without a corresponding increase of ischaemic events with a strategy of ticagrelor monotherapy compared with DAPT represents a finding of utmost importance,” write Dirk Sibbing (Ludwig-Maximilians University, Munich, Germany) and Salvatore Cassese (German Heart Center Munich, Munich, Germany) in an editorial comment accompanying the study in JACC: Cardiovascular Interventions. “A strategy of dropping P2Y12 inhibitors in favour of aspirin after coronary stenting has been extensively investigated, but there is only a handful of randomised trials testing the discontinuation of aspirin instead of P2Y12 inhibitors in this setting.”
Sibbing and Cassese conclude that given the potential of P2Y12 inhibitor monotherapy to reduce the risk of bleeding without an ischaemic trade-off compared with DAPT in patients treated with PCI, the number of studies evaluating this therapeutic approach is expected to increase in the years to come.
The add that the present study lends support to superior safety and comparable efficacy of ticagrelor monotherapy compared with ticagerlor or clopidogrel after coronary stenting.