De-escalation to ticagrelor monotherapy does not increase ischaemic risk and reduces the risk of major bleeding when compared to 12 months of dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI), particularly among patients with acute coronary syndromes (ACS).
This was the finding of a systematic review and individual patient data (IPD)-level meta-analysis of randomised trials comparing the safety and efficacy of ticagrelor monotherapy after short-term DAPT versus 12 months of DAPT in patients who have undergone PCI with a drug-eluting stent.
Findings of the analysis were shared on behalf of the Single Versus Dual Antiplatelet Therapy (Sidney-4) collaborator group at the European Society of Cardiology (ESC) 2024 annual meeting (30 August–2 September, London, UK) and published simultaneously in The Lancet.
DAPT is currently recommended as the default antiplatelet regimen after coronary drug-eluting stent implantation, the authors, Marco Valgimigli (Cardiocentro Ticino Foundation, Lugano, Switzerland) and colleagues, note in their Lancet paper, but some studies have shown that from a few weeks to a few months after initiation of DAPT, de-escalation of treatment to a strategy of P2Y12 inhibitor monotherapy does not increase ischaemic risk and is associated with less bleeding compared with continuation of standard DAPT.
The authors note, however, that these studies can be difficult to interpret due to differing study design, patient populations, and types of P2Y12 inhibitor used, and have insufficient power to estimate the treatment effect on relevant individual endpoints, such as mortality or stent thrombosis, or in sub-groups.
After analysing all available randomised evidence on DAPT de-escalation to ticagrelor monotherapy, investigators selected data from six randomised trials with centrally adjudicated endpoints that assigned patients to ticagrelor monotherapy or DAPT, representing more than 24,000 patients in total.
For the three ranked coprimary endpoints—a composite of all-cause death, myocardial infarction, or stroke—the investigators were able to demonstrate that the DAPT de-escalation strategy met non-inferiority.
The risks of Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding and all-cause death were lower with ticagrelor monotherapy compared with DAPT. Trial sequential analysis showed robust evidence of non-inferiority for major adverse cardiovascular or cerebrovascular events (MACCE) and superiority for bleeding among the overall and ACS populations.
The treatment effects for MACCE were heterogeneous by sex, suggesting a benefit in women administered ticagrelor monotherapy, and by clinical presentation for BARC 3 or 5 bleeding, indicating a benefit in ACS with ticagrelor monotherapy, the investigators report.
“The present IPD meta-analysis provides evidence that de-escalating from DAPT to ticagrelor monotherapy from a few weeks to a few months after coronary drug-eluting stent implantation does not increase fatal and non-fatal ischaemic risk, and significantly reduces the risk of major bleeding compared with 12 months of DAPT in patients with ACS,” the study’s authors write. “There was a significant, yet inconclusive, mortality benefit with ticagrelor, particularly among women, which warrants further investigation. However, in patients with CCS [chronic coronary syndrome], the benefits and risks of DAPT de-escalation to ticagrelor monotherapy compared with continued DAPT remain unestablished.”
