Pharmacodynamic Outcomes in CCS Patients Treated With an Individualized Treatment Strategy

• Status: Not yet recruiting
• Trial end date: 2025-05-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: St. Antonius Hospital
• Treatments: Clopidogrel; Prasugrel Hydrochloride; Ticagrelor

Criteria

Inclusion Criteria:

• Patients ≥ 18 years of age

• Patients with CCS undergoing successful elective PCI

• Patients with written informed consent as approved by the ethics committee

Exclusion Criteria:

• Contraindication to aspirin, ticagrelor, prasugrel or clopidogrel

• Under the age of 18 years

• Planned cardiac valve surgery

• Need for chronic oral anticoagulation

• PCI when admitted for ACS

• Life expectancy < 1 year

• Unable or unwilling to provide informed consent

• Pregnancy

• Suboptimal result of stenting as defined by the operator, preferably explained according the complex-PCI criteria

• Treatment with a strong CYP3A4 inhibitor or inducer

• Treatment with a strong CYP2C19 inhibitor or inducer

• History of definite stent thrombosis