KEY POINTS:
- Ticagrelor monotherapy was found to be non-inferior to 12 months of dual-antiplatelet therapy (DAPT) regarding major cardiovascular and cerebrovascular events (MACCE) in patients with acute coronary syndrome (ACS)
- A superiority analysis revealed lower bleeding rates in a per-protocol analysis with ticagrelor monotherapy versus DAPT in ACS patients
DAPT is the standard of care after percutaneous intervention (PCI) followed by de-escalation to anti-platelet monotherapy. Historically, aspirin monotherapy has been the default option, however, several studies have demonstrated benefit from P2Y12 inhibitor monotherapy and with shorter courses of DAPT. Previous work from the TWILIGHT trial published in 2019 suggested that a shorter duration of DAPT followed by ticagrelor monotherapy decreased bleeding and ischemic risk.
This systematic review utilized individual patient data from randomized clinical trials to evaluate whether ticagrelor monotherapy after a brief period of DAPT post-PCI resulted in fewer ischemic and bleeding events compared to 12 months of DAPT. Three ranked co primary endpoints were selected. A hierarchical analysis was performed, beginning with a non-inferiority, intention-to-treat analysis of MACCE (all cause death, MI, or stroke) for non-inferiority, followed by a per-protocol ranked superiority testing of major bleeding (BARC type 3 or 5) and all-cause death as superiority.
The review incorporated data from six trials with over 24,000 participants (median age of 64 and 22.6% female). The median duration of DAPT was 78 days, with an interquartile range of 31 to 92 days. The majority of patients presented with acute coronary syndromes. Participants with a need for anti-coagulation were excluded.
The composite MACCE endpoint occurred in 2.8% in the ticagrelor monotherapy group and 3.2% in the DAPT group (HR 0.91 [95% CI 0.78-1.07], p=0.0039 for non-inferiority). The benefit was observed in the acute coronary syndrome subgroup, as well as among females and diabetics.
The bleeding endpoint, defined as type 3 and 5 BARC, occurred in 0.9% of the ticagrelor group and 2.1% in the DAPT group (HR 0·43 [ 95% CI 0·34–0·54]; p<0·0001 for superiority). The superiority on mortality was also seen (HR 0,76 :95% CI 0.59-0.98; p=0,034). A trial sequential analysis shown conclusive results for MACCE and major bleeding, but not for all cause of death. Results were consistent across the different subgroups tested.
There were several limitations of this study. First, the study included open label trials as well as double blind ones. Secondly, participants in the DAPT group were prescribed various regimens that included clopidogrel or ticagrelor in addition to aspirin. Lastly, participants in the DAPT group were required to undergo 12-months of DAPT, which is longer than the typical 6 month course post ACS.
The authors concluded that this meta analysis provides evidence that DAPT de-escalation to ticagrelor monotherapy , at a median of 2 weeks to 3 months after DES implantation, preserves fatal and non-fatal ischemic events and halves major bleeding rates compared to 1 year DAPT.