Ischaemic events following planned discontinuation of study treatment with ticagrelor or clopidogrel in the PLATO study

Abstract

Purpose: Acute coronary syndrome patients in the PLATO study were randomised to receive ticagrelor (T) or clopidogrel (C) for up to 12 months following which study medication was discontinued and it was left to investigator discretion as to subsequent antiplatelet therapy. Different mechanisms of receptor inhibition underlie the more rapid offset of action of T compared to C, with significantly greater recovery at 3 days post dose. Increase in the frequency of ischaemic events has been reported following discontinuation of antiplatelet therapy. We compared the rates of ischaemic events in the PLATO study following planned discontinuation of study medication with either T or C. Methods: PLATO study patients were included in this analysis if they met all of the three following criteria: (1) received at least one dose of study medication; (2) completed their course of study medication prior to discontinuation; and (3) did not have an endpoint of interest up to 2 days after the last dose of study medication. 30‐day K‐M rates of the primary composite endpoint of CV death, non‐fatal MI or non‐fatal stroke as well as individual components of this endpoint were determined for events occurring between 2 and 32 days after last dose of study medication. Event rates up to 2 days post discontinuation as well as during treatment were assessed by separate analyses. Results: 6330 T and 6394 C patients completed study medication and did not have a primary endpoint event prior to, and up to 2 days following, planned discontinuation of study medication. Approximately one‐third in each group subsequently received open‐label clopidogrel, over 95% received aspirin and less than 1% received no antiplatelet drug. The primary endpoint occurred in 19 (0.3%) T patients and 22 (0.3%) C patients within the subsequent 30 days (P = ns). MI occurred in 8 (0.1%) T vs 4 (0.1%) C patients (P = ns) and CV death occurred in 16 (0.3%) T vs 21 (0.3%) C patients (P = ns). There were no strokes in either group. There was also no difference between the groups in event rates up to 2 days post discontinuation. Primary endpoint rates over 30 days following visits at 6 and 9 months, for patients who continued study medication following these visits, were similar to primary endpoint rates following planned discontinuation after study completion. Conclusions: No differences in ischaemic events were seen following study completion and planned discontinuation of T compared to C. There was no evidence of a rebound increase in ischaemic events after discontinuation.