Pharmacodynamic Outcomes in CCS Patients Treated With an Individualized Treatment Strategy
Status:
Not yet recruiting
Trial end date:
2025-05-01
Target enrollment:
Participant gender:
Summary
Patients with Chronic Coronary Syndrome (CCS) undergoing with elective percutaneous coronary
intervention (PCI) are treated with dual antiplatelet therapy (DAPT), consisting of aspirin
combined with clopidogrel for 6 months. The aim of DAPT is to prevent recurrent thrombotic
events, i.e. death, stent thrombosis and/ or myocardial infarction (MI). However, the
trade-off of thrombotic prevention by DAPT is an increased risk of bleeding.
Multiple strategies to reduce bleeding risk and optimize outcomes have been proposed. On one
hand the bleeding risk can be reduced by shortening the duration of DAPT and omitting
aspirin. This has been proven effective in patients with acute coronary syndromes (ACS)
compared to standard DAPT, without a significant difference in thrombotic events. On the
other hand, personalized medicine by means of genotyping to ensure that a patient is treated
with an, for them, effective drug, can be a strategy to optimize patients outcomes. In CCS
patients the preferred P2Y12-inhibitor is clopidogrel. However, clopidogrel must first be
activated by the CYP2C19 enzyme in the liver. Only then can clopidogrel inhibit the
P2Y12-receptor and prevent platelet activation. Almost thirty percent of patients has a
genetic variation of the gene encoding this CYP2C19 enzyme. In these patients, clopidogrel is
not or hardly activated, putting them at a higher risk of thrombotic events than patients who
do not have this gene variation. By determining the CYP2C19 genotype, it is possible to
estimate whether clopidogrel will be effective or not.
In this trial we evaluate the pharmacodynamic effects of genotype guided P2Y12-inhibitor
monotherapy in patients with CCS undergoing PCI. In the intervention arm the CYP2C19 genotype
will be assessed using a point-of-care test device on the cardiology ward, which can be
performed by (research) nurses. Patients with a CYP2C19 loss-of-function (LOF) allel will be
treated with monotherapy ticagrelor or prasugrel. Patients who are non-carrier of a LOF allel
will receive clopidogrel. The control arm will be treated with the current standard-of-care,
which is DAPT, consisting of aspirin combined with clopidogrel for 6 months.
The main goals is to assess the antithrombotic effects of individualized P2Y12 monotherapy
strategy versus clopidogrel plus aspirin in elective PCI patients.