At a glance
ClinicalIndex Comparison Record- ✓Atherosclerotic cardiovascular disease (prior ACS, MI, angina, revascularization, stroke, TIA, or PAD)
- ✓On clopidogrel 75 mg daily for ≥30 days, with or without low-dose aspirin 81 mg daily
- ✓High on-treatment platelet reactivity (HPR): P2Y12 reaction units >208 by VerifyNow P2Y12
- ✓Fasting LDL-cholesterol ≥70 mg/dL or non-HDL-C ≥100 mg/dL on stable statin therapy (≥2 weeks)
- ✕Current use of oral anticoagulants (vitamin K antagonists, dabigatran, rivaroxaban, apixaban, edoxaban)
- ✕Antiplatelet agents other than aspirin and clopidogrel within past 14 days
- ✕PCSK9 inhibitor use within past 90 days
- ✕Creatinine clearance <30 mL/minute
Standardized by ClinicalIndex from the ClinicalTrials.gov record · verify against the source.
Impact of the PCSK9 Inhibitor Evolocumab on the Pharmacodynamic Effects of Clopidogrel in Patients With Atherosclerotic Cardiovascular Disease and High On-Treatment Platelet Reactivity
In Brief
A Phase 4 clinical trial evaluating Evolocumab and Placebo for Atherosclerotic Cardiovascular Disease. Completed, enrolled 259 participants across 1 site.
Detailed 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.
Study Details
Timeline
Interventions
Patients will be randomly assigned to receive a single dose of either evolocumab 420 mg s.c. or placebo (0.9% sodium chloride s.c. injection).
Patients will be randomly assigned to receive a single dose of either evolocumab 420 mg s.c. or placebo (0.9% sodium chloride s.c. injection).