Patients who suffered from acute coronary syndrome (ACS) are usually treated with a long-term dual antiplatelet therapy (DAPT) to reduce stent thrombosis and recurrent ischemic event. Nonetheless, recent important data have demonstrated the efficacy of a short term DAPT and an early single antiplatelet therapy in high bleeding and ischemic risk patients. The bleeding risk is associated with a significant mortality. This risk is especially high in patients treated with potent P2Y12 inhibitors like ticagrelor or prasugrel after an ACS. As a result of the abounding data regarding the safety of an early single antiplatelet therapy with high potency antiplatelet therapy (ticagrelor or prasugrel), it is likely that such strategy will soon be implemented in the guidelines. The benefits of these high-potency P2Y12 inhibitors over clopidogrel mostly occur in patients with genetic polymorphisms of CYP2Y12 associated with a loss of function in clopidogrel metabolism. Furthermore, the anti-ischemic benefit of potent P2Y12 inhibitors over clopidogrel occurs early, while excess bleeding events often arise during chronic treatment. Our hypothesis is that a systematic and rapid genetic screening of CYP2C90 \*2 or \*17 polymorphism to guide an early single therapy with low potency antiplatelet (aspirin or clopidogrel) could lead to less bleeding events with a consistent efficacy towards cardiac events compared with high potency antiplatelet therapies (prasugrel or ticagrelor) in high bleeding risk patients treated for ACS.
Multicenter, randomized, open label trial using the PROBE study design. Randomization 1 to 3 months (preferably 1, considering the HBR) after ACS into 2 parallel arms. Stratification: according to revascularization status (PCI or no PCI), genotype (loss of function, fast metabolization, none) and center. Control arm: stop aspirin for a single antiplatelet therapy with a high-potency antiplatelet (ticagrelor or prasugrel). Intervention arm: single-antiplatelet with a low-potency antiplatelet (aspirin or clopidogrel) guided by genetic testing.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
SINGLE
Enrollment
2,468
* Individuals without genetic loss of function to metabolize clopidogrel (\*1/\*1, \*2/\*17, \*3/\*17): stop DAPT and switch to a single antiplatelet therapy by clopidogrel. * Individuals with genetic loss of function to metabolize clopidogrel (\*2/\*3, 1/\*3, \*2/\*2, \*1/\*2,\*3/\*3): stop potent P2Y12 inhibitor and treat with a single antiplatelet therapy by aspirin. * Individuals with fast metabolization of clopidogrel (\*1/\*17 or \*17/\*17): stop potent P2Y12 inhibitor and treat with a single antiplatelet therapy by aspirin.
Hopital Pitié Salpetrière
Paris, IDF, France
RECRUITINGRate of combinated major and minor bleeding events (BARC 2 to 5 BARC)
the occurrence of major or minor bleeding events between randomization to one of the de-escalation strategies and 1 year after index ACS defined according to the Bleeding Academic Research Consortium (BARC) classification as type 2 to 5
Time frame: From randomization (1-3months after inclusion) to 1year after inclusion
Rate of major adverse cardiovascular events
major adverse cardiovascular events defined as follow and in the following hierarchical order: * Death or myocardial infarction or stroke or stent thrombosis (key secondary) * Death or Myocardial infarction
Time frame: From randomization to de-escalation (1-3months) to 1year
Rate of major bleeding events
the occurrence of major bleeding events between randomization to one of the de-escalation strategies and 1 year after index ACS defined according to the Bleeding Academic Research Consortium (BARC) classification
Time frame: randomization to de-escalation (1-3months) to 1year
Rate of minor bleeding events
the occurrence of minor bleeding events between randomization to one of the de-escalation strategies and 1 year after index ACS defined according to the Bleeding Academic Research Consortium (BARC) classification
Time frame: randomization to de-escalation (1-3months) to 1year
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