This investigation will be conducted in subjects \>18 years of age with PAD. Platelet activation and aggregation, and biomarkers associated with platelet activation, oxidative stress, and inflammation will be assessed prior to initiation of study-HD statin therapy (baseline), after 8 weeks of high-dose statins and 24 hours and 8 weeks after high dose statin + evolocumab therapy
Monoclonal antibodies against PCSK9 are innovative agents that provide very potent LDL reduction when administered on top of statins. PCSK9 antibodies prevent LDL receptor degradation and enhance circulatory LDL cholesterol clearance. High LDL is a major risk factor for PAD and therefore lipid-lowering therapy constitutes another important therapeutic intervention for patients with PAD. Evolocumab is a common PCSK-9 inhibitor that has been shown to reduce plasma LDL. In this study sixty subjects will be treated with high dose statins for 8 weeks followed by 8 weeks of high dose statin + evolocumab (420mg/4 wk) therapy to determine the effect of Repatha on markers of cholesterol, thrombosis, and inflammation.
Study Type
OBSERVATIONAL
Enrollment
30
Sixty subjects will be treated with high dose statins for 8 weeks followed by 8 weeks of high dose statin + evolocumab (420mg/4 wk) therapy.
Inova Fairfax Hospital
Falls Church, Virginia, United States
Difference Between ADP-induced % Maximum Platelet Aggregation Between V2 (After 8 Weeks of HD Statin Therapy) and V5 (8 Weeks of Continued HD Statin Therapy + Evolocumab)
Mean difference between 5uM ADP-induced % maximum platelet aggregation between V2 \[after run-in period / 8 weeks of HD statin therapy\] and V5 \[end of study/ 8 weeks o\]f continued HD statin therapy + evolocumab\]
Time frame: Change from week 8 (V2) to week 16 (V5)
Difference Between Collagen-induced Platelet Aggregation Between V2 (After 8 Weeks of HD Statin Therapy) and V5 (8 Weeks of Continued HD Statin Therapy + Evolocumab)
Mean difference between 4ug Collagen-induced platelet aggregation (%) between V2 \[after run-in period / 8 weeks of HD statin therapy\] and V5 \[end of study/ 8 weeks of continued HD statin therapy + evolocumab\]
Time frame: Change from week 8 (v2) to week 16 (v5)
Difference Between SFFLRN-induced Platelet Aggregation Between V2 (After 8 Weeks of HD Statin Therapy) and V5 (8 Weeks of Continued HD Statin Therapy + Evolocumab)
Mean difference between SFFLRN-induced maximum platelet aggregation (%) between V2 \[after run-in period / 8 weeks of HD statin therapy\] and V5 \[end of study/ 8 weeks of continued HD statin therapy + evolocumab\]
Time frame: Change from week 8 (v2) to week 16 (v5)
Difference Between Activated % P-selectin Positive Platelets Between V2 (After 8 Weeks of HD Statin Therapy) and V5 (8 Weeks of Continued HD Statin Therapy + Evolocumab)
Mean difference in activated % P-selectin positive platelets between V2 \[after run-in period / 8 weeks of HD statin therapy\] and V5 \[end of study/ 8 weeks o\]f continued HD statin therapy + evolocumab\]
Time frame: Change from week 8 (v2) to week 16 (v5)
Difference in TEG MAKH Between V2 (After 8 Weeks of HD Statin Therapy) and V5 (8 Weeks of Continued HD Statin Therapy + Evolocumab)
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Mean difference TEG MAKH (platelet-fibrin clot strength) between V2 \[after run-in period / 8 weeks of HD statin therapy\] and V5 \[end of study/ 8 weeks of continued HD statin therapy + evolocumab\] Thromboelastography (TEG) is a viscoelastic hemostatic assay that measures the global viscoelastic properties of whole blood clot formation under low shear stress. TEG shows the interaction of platelets with the coagulation cascade (aggregation, clot strengthening, and fibrin cross-linking). MAKH is a measure of maximum platelet-fibrin clot strength. The normal range for MAKH is 53-68mm.
Time frame: Change from week 8 (v2) to week 16 (v5)