LAUSR

Following an acute coronary syndrome (ACS), patients remain at risk for new ischaemic events, regardless of the type of presentation or the initial management. Although a substantial proportion of the recurrent events occur in the first months, there is a continuing accruement of new ischaemic events afterwards. As a consequence, guidelines recommend a P2Y12 inhibitor to be added to low-dose aspirin for the first year following an ACS, whether or not a percutaneous coronary intervention (PCI) is performed, and to continue low-dose aspirin alone indefinitely. The recommended duration of 1 year of dual antiplatelet therapy (DAPT) after an ACS is arbitrarily based on the treatment duration in the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial, the first outcome trial on DAPT in ACS. Because DAPT puts ACS patients at an increased risk of bleeding complications, P2Y12 inhibitors are often deliberately discontinued before 1 year because of the occurrence of bleeding or a perceived or real high bleeding risk. On the other hand, registries have shown, surprisingly, that in a significant proportion of ACS patients DAPT is continued beyond 1 year because neither ischaemic nor bleeding events had occurred (the ‘never change a winning team’ approach). The superiority of ticagrelor and prasugrel over clopidogrel in the first year following an ACS has been clearly established in two pivotal large international trials. Landmark analyses of these trial data show a greater reduction in recurrent ischaemic events with these new agents throughout the year following the event, thus not only during the acute phase but also afterwards. Ticagrelor and prasugrel (the latter with some restrictions) are hence unequivocally recommended on top of low-dose aspirin for 1 year after an ACS. Clopidogrel only remains a recommended option for ACS patients without access to either ticagrelor or prasugrel. Still, ever since these trials, cardiologists have wondered whether tiered, step-wise approaches could be as effective and perhaps safer than the guidelines recommendations. One option among many, for instance, is switching to clopidogrel at discharge or a few weeks later instead of continuing prasugrel or ticagrelor. Issues with reimbursement or availability, or with a perceived bleeding risk are assumed to justify a switch to the less potent and cheaper P2Y12 inhibitor clopidogrel. In this issue of the journal, Cuisset and colleagues report the results of the Timing Of Platelet Inhibition after acute Coronary syndrome (TOPIC) study, the first randomized clinical trial investigating a switch from prasugrel or ticagrelor to clopidogrel vs. continuing either drug after a PCI for ACS. A total of 646 patients with an STsegment elevation myocardial infarction (STEMI), non-STEMI, or unstable angina who did not experience an ischaemic or bleeding event in the first 30 days after the event were then randomized to either strategy. One year after the ACS, significantly more patients who continued their more potent P2Y12 inhibitor experienced the combined endpoint of cardiovascular death, stroke, unplanned hospitalization leading to revascularization, or a Bleeding Academic Research Consortium (BARC) bleeding category of >_2 compared with those switching to clopidogrel. With very low numbers of ischaemic events or Thrombolysis In Myocardial Infarction (TIMI) major bleeding complications, not unexpectedly this difference was mainly driven by fewer non-major bleedings including the relatively innocuous BARC type 2 bleedings, i.e. harmless bleedings leading to medical attention. The number of BARC type 2 bleedings was not reported separately. There was even a non-significant numerical excess in ischaemic events in patients continuing ticagrelor or prasugrel. Most of these events were unplanned revascularizations however, and the proportion of patients who needed a new intervention because of a new spontaneous MI was not reported, nor was the