Use of potent P2Y12 receptor inhibitors like prasugrel or ticagrelor has improved clinical outcomes in patients with acute coronary syndrome undergoing percutaneous coronary intervention (PCI), albeit at the expense of an increased bleeding risk. The greatest benefits of these medicines are seen early, when the risk of complications is highest, whereas the bleeding risk is seen more with chronic treatment. There has therefore been interest in the use of de-escalation strategies, where patients are treated initially with potent P2Y12 receptor inhibitors, and then switched to clopidogrel (less potent) during the chronic phase. Although this is seen in current practice, data so far on such strategies are limited and conflicting.
The current study investigated a de-escalation regimen of one week of prasugrel, followed by one week of clopidogrel, and then maintenance therapy with clopidogrel or prasugrel guided by platelet function testing (about 60% of patients continued on clopidogrel and 40% required escalation back to prasugrel). Non-inferiority was demonstrated for net clinical benefit (cardiovascular death, myocardial infarction, stroke or bleeding grade 2 or higher according to Bleeding Academic Research Consortium [BARC]) criteria) at one year after randomisation. The non-inferiority margin was 30% and this was met; superiority was also tested but this did not reach statistical significance.
This is the first randomised study to test platelet function testing-guided de-escalation therapy in patients with acute coronary syndrome undergoing PCI. Although it did not demonstrate superiority to standard therapy of prasugrel, it could be an alternative option for patients who are not suitable for prolonged therapy with potent P2Y12 inhibitors (e.g. those at increased risk of bleeding). There are however some limitations acknowledged, including potential confusion for patients if having to switch to and fro (if escalation is required), and the requirement for access to centres that can access platelet function testing. Also it is not known if the findings of this study can be extrapolated to ticagrelor, or to the patient groups excluded from participation (e.g. the elderly; those with a previous cerebrovascular event).
The authors of a related editorial conclude that “Future research should build upon TROPICAL-ACS to help to define antiplatelet treatment approaches associated with optimal safety and efficacy performance profiles for the individual patient.”