Ignite Creation Date:
2024-05-06 @ 9:52 AM
Last Modification Date:
2024-10-26 @ 12:21 PM
Study NCT ID:
NCT03096288
Status:
COMPLETED
Last Update Posted:
2022-02-17
First Post:
2017-03-23
Brief Title:
Impact of Evolocumab on the Effects of Clopidogrel in Patients With High On-Treatment Platelet Reactivity
Sponsor:
University of Florida
Organization:
University of Florida
Study Overview
Official Title:
Impact of the PCSK9 Inhibitor Evolocumab on the Pharmacodynamic Effects of Clopidogrel in Patients With Atherosclerotic Cardiovascular Disease and High On-Treatment Platelet Reactivity
Status:
COMPLETED
Status Verified Date:
2022-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 subtilisinkexin 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
Evolocumab is a monoclonal antibody targeting proprotein convertase subtilisinkexin 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
Detailed Description:
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 Although the efficacy of DAPT with aspirin and clopidogrel has been consistently shown in different clinical settings rates of ischemic recurrences remain elevated despite this treatment regimen especially in high risk patients This has been in part attributed to the high interindividual variability in responses to clopidogrel 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 in particular stent thrombosis in patients with ACS and following PCI This underscores the need for strategies aimed to reduce HPR rates in patients treated with clopidogrel Multiple approaches have been advocated to reduce HPR rates The pleiotropic effects associated with lipid lowering therapies in particular statins have been subject to extensive research 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 subtilisinkexin type 9 PCSK9 that is administered subcutaneously sc at a dosage of 140 mg every 2 weeks or 420 mg once monthly In clinical trials evolocumab was more effective than placebo andor ezetimibe in reducing LDL cholesterol including when added to statin therapy 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
Evolocumab is a monoclonal antibody targeting proprotein convertase subtilisinkexin type 9 PCSK9 that is administered subcutaneously sc at a dosage of 140 mg every 2 weeks or 420 mg once monthly In clinical trials evolocumab was more effective than placebo andor ezetimibe in reducing LDL cholesterol including when added to statin therapy 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None