Amarin Corp Plc (AMRN)

[Whalatane]

Capt. Thx. I remember there being a lot of discussion around the optimal serum EPA levels as levels over the 4 gms daily used in R-IT may increase risk .
Theres this concept of therapeutic window .....high enough dose to confer benefit but not high enough to significantly increase risk / ae's

Anti-platelet effects: EPA has been shown to reduce platelet aggregation and adhesion to fibrinogen and collagen. This inhibits platelet activation and the formation of a stable clot, which can increase bleeding risk.
Inhibition of thrombin formation: EPA alters the phospholipid membrane of platelets, inhibiting the platelet membrane from forming the coagulation cascade complex at sites of vascular injury. This decreases thrombin and clot formation.
Reduced platelet pseudopodia formation: High EPA levels can reduce the formation of platelet pseudopodia, the projections that allow platelets to adhere and aggregate during clot formation.
Dose-response relationship: Studies like REDUCE-IT showed that higher on-treatment serum EPA levels achieved with higher doses were associated with greater reductions in cardiovascular events, but also a "nonsignificant trend in increased bleeding events." This suggests very high EPA levels may be required for maximum benefit but also carry higher bleeding risk.
Effects on coagulation cascade: While the exact mechanisms are unclear, EPA may inhibit platelet-mediated thrombin formation, preventing occlusive thrombus formation but potentially increasing bleeding risk.
So in summary, the anti-thrombotic and anti-platelet effects of high serum EPA levels, especially at the higher doses used in trials like REDUCE-IT, appear to underlie the observed increase in bleeding risk by impairing normal hemostasis and clot formation.

Kiwi