P328Is there evidence of a rebound increase in platelet aggregation following withdrawal of Aspirin or Ticagrelor in patients who have previously undergone PCI and coronary stenting?
Authors: Hennigan B W , Good R , Adamson C , Martin L , Anderson L , Campbell M , Oldroyd K G 
Published: October 2019

Abstract

Introduction
In patients treated with coronary stents previous studies have demonstrated an increased risk of acute coronary syndrome in after discontinuation of clopidogrel. In this study, we recruited patients already randomised in the GLOBAL LEADERS study allocated to discontinue aspirin treatment, while remaining on ticagrelor, 1 month after coronary stenting (Ticag MonoRx group) and a control group discontinuing ticagrelor at 6–12 months while remaining on aspirin (ASA MonoRx group). Both groups underwent platelet studies at day 0, prior to discontinuation of aspirin or ticagrelor and then on day 2, 7 and 14 day post cessation with multiple electrode aggregometry.

Purpose
This study was designed to look for evidence of a rebound increase in platelet aggregation in response to collagen after withdrawal of either aspirin or ticagrelor in patients who have been treated with both drugs after PCI with DES implantation. We needed a sample size of 26 patients in each group for 90% power to detect a mean change in platelet aggregation of 100 AU/min with an alpha of 0.05. The primary outcome measure was change in platelet aggregation in response to collagen between baseline and day 2, day 7 and day 14 following cessation of DAPT. A rebound effect was defined as a >10% increase in collagen induced platelet aggregation on either day 2 or day 7 compared to day 14 post discontinuation of either aspirin or ticagrelor.

Methods
Patients provided written informed consent and underwent MEA using arachidonic acid (AA), adenosine diphosphate (ADP), thrombin receptor activator peptide (TRAP) and collagen in prespecified concentrations timed at 30 mins post phlebotomy. Results were calculated from the area under the curve and expressed as as whole number aggregation units (AU). Inbuilt QC analysis was used to determine the need for repeat assays.

Results
Collagen induced platelet aggregation was similar in both groups at day 0 (37 AU vs 34 AU; p=0.687) and at day 2 (55 AU vs 40 AU; p=0.12). By day 7, patients on ticagrelor monotherapy had higher collagen induced platelet aggregation (78 AU vs 37 AU; p=0.0001) and this difference was maintained at 14 days (80 AU vs 43 AU; p=0.0001). In patients, assigned to ticagrelor monotherapy after 1 month of DAPT, AA induced platelet aggregation progressively increased from day 0 to day 14. In the patients discontinuing ticagrelor and continuing on aspirin monotherapy, ADP induced platelet aggregation increased from day 0 to day 14. Rebound was seen in 6/17 (35%) patients in the ticagrelor monotherapy group versus 8/17 (47%) patients in the aspirin monotherapy group (p=0.728) with a mean peak of 21 AU (SD 6) and 10 AU (SD 6) respectively above baseline readings, p=0.003. There was no difference in TRAP induced aggregation at any time point.
Figure 1

Conclusions
Ticagrelor monotherapy was associated with higher collagen induced platelet aggregation than aspirin monotherapy at both 7 and 14 days post cessation of DAPT.

Acknowledgement/Funding
British Heart Foundation Project Grant PG/14/97/31263, AstraZeneca UK Limited