Impact of Evolocumab on the Effects of Clopidogrel in Patients With High On-Treatment Platelet Reactivity
Status:
Completed
Trial end date:
2020-11-02
Target enrollment:
Participant gender:
Summary
Clopidogrel is the most widely used P2Y12 receptor inhibitor and is the only agent of this
class currently recommended in patients with stable coronary artery disease (CAD) undergoing
PCI, and for the treatment of stroke or PAD. Pharmacodynamic (PD) studies have shown that
approximately 30-40% of patients experience high on-treatment platelet reactivity (HPR) while
receiving clopidogrel treatment. Importantly HPR status has been strongly associated with an
increased risk of ischemic events. Multiple approaches have been advocated to reduce HPR
rates. In a previous study treatment with high-dose atorvastatin in addition to double-dose
clopidogrel reduced platelet reactivity significantly more than double-dose clopidogrel alone
in statin-naïve patients with stable CAD and HPR. To date, the exact biological mechanisms
involved in the statin modulation of platelet function are not fully understood, although
likely attributed to both its lipid-lowering and non-lipid-related effects.
Evolocumab is a monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9
(PCSK9). The use of evolocumab plus standard therapy, as compared with standard therapy
alone, significantly reduced the incidence of cardiovascular events. Whether the reduction in
cardiovascular events is simply due to LDL reduction or might be related to other mechanisms
is currently subject of investigation. Although LDL reduction with statin therapies has been
associated with reduction in platelet reactivity, to date the effects on platelet aggregation
of adjunctive lipid lowering with evolocumab has not been explored.
The aim of the present study is to investigate the effects of evolocumab in addition to
statin therapy on HPR rates and platelet reactivity in patients with atherosclerotic
cardiovascular disease (ASCVD) and HPR while on clopidogrel treatment.