Research in context
Evidence before this study
The current guidelines recommend the use of potent P2Y12 receptor inhibitors over clopidogrel for up to 1 year in patients with acute myocardial infarction undergoing percutaneous coronary intervention (PCI). Although the ischaemic risk is greater in the early phase, the bleeding risk remains high during the maintenance phase of acute myocardial infarction. These findings have resulted in the development of a stepwise de-escalation of dual antiplatelet therapy (DAPT) by means of a potent P2Y12 inhibitor only in the acute phase and the less potent clopidogrel during the chronic phase of treatment. We searched PubMed on May 1, 2021, for articles published in English, with the search terms “dual antiplatelet therapy”, “antiplatelet treatment de-escalation”, “switching antiplatelet therapy”, “acute coronary syndrome”, and “percutaneous coronary intervention”. Our search identified only a few relevant randomised, clinical trials that investigated this issue. Unlike ticagrelor monotherapy trials such as TWILIGHT and TICO, and a study using reduced dose of prasugrel, the HOST-REDUCE-POLYTECH-ACS trial, multiple options of de-escalation dual antiplatelet therapy exist: unguided, platelet function test-guided, and CYP2C19 genotype-guided. In the TROPICAL-ACS study, the de-escalation strategy of switching to clopidogrel guided by platelet function test was non-inferior to prasugrel-based DAPT in terms of net clinical benefit. However, the complexity of the testing and protocols are impractical in clinical practice. The POPular Genetics trial adopting CYP2C19 genotype-guided strategy for selection of an appropriate P2Y12 inhibitor showed a lower incidence of bleeding but has similar weakness to that of the TROPICAL-ACS study. Although data on the unguided de-escalation DAPT switching from potent P2Y12 inhibitors to clopidogrel are scarce, unguided de-escalation commonly occurs in clinical practice.
Added value of this study
The Ticagrelor versus Clopidogrel in Stabilized Patients with Acute Myocardial Infarction (TALOS-AMI) trial investigated the hypothesis that de-escalation DAPT with clopidogrel might be non-inferior to ticagrelor-based antiplatelet therapy in stabilised patients with acute myocardial infarction. In 2697 patients with acute myocardial infarction who had no major ischaemic or bleeding events and tolerated aspirin plus ticagrelor therapy during the first month after an index PCI, a uniform unguided de-escalation antiplatelet therapy switching from ticagrelor to clopidogrel was superior to the ticagrelor-based continuing DAPT in terms of net clinical benefit (a composite of cardiovascular death, myocardial infarction, stroke, and bleeding type 2, 3, or 5 according to Bleeding Academic Research Consortium (BARC) criteria from 1 to 12 months after the index PCI. The de-escalation strategy was associated with a 45% lower risk of net clinical benefits for the next 11 months than the ticagrelor-based dual antiplatelet strategy. The absolute risk reduction was 3·6%, which was mainly caused by a significant decrease in bleeding risk. Additionally, a composite of BARC 3 or 5 bleeding occurred less frequently in the de-escalation group but was marginally significant. Even a composite of ischaemic events and serious bleeding such as BARC bleeding type 3 or 5 showed a significant difference between the two groups. In this study, the incidence of primary ischaemic events from 1 to 12 months after an index event were similar to those of other de-escalation trials including the TROPICAL-ACS, TWILIGHT-ACS, POPular Genetics, and TWILIGHT trials, which might indicate the safety of a uniform unguided de-escalation antiplatelet strategy in stabilised patients with uncomplicated acute myocardial infarction.
Implications of all the available evidence
In stabilised patients with acute myocardial infarction who had no major ischaemic or bleeding events and tolerated aspirin plus ticagrelor therapy during the first month after an index PCI, a uniform unguided de-escalation antiplatelet strategy switching from ticagrelor to clopidogrel was superior to the ticagrelor-based DAPT strategy at preventing net adverse clinical events, including the thrombotic composite and clinically relevant bleeding.