Abstract
Lipid-lowering agents and antiplatelet drugs are guideline-recommended standard treatment
for secondary prevention of acute thrombotic events in patients with increased cardiovascular
risk. Aspirin is the most frequently used antiplatelet drug, either alone or in combination
with other antiplatelet agents (P2Y12 inhibitors), while statins are first-line treatment of hypercholesterolemia. The
well-established mode of action of aspirin is inhibition of platelet-dependent thromboxane
formation. In addition, aspirin also improves endothelial oxygen defense via enhanced
NO formation and inhibits thrombin formation. Low-dose aspirin exerts in addition
anti-inflammatory effects, mainly via inhibition of platelet-initiated activation
of white cells.
Statins inhibit platelet function via reduction of circulating low-density lipoprotein-cholesterol
(LDL-C) levels and a more direct inhibition of platelet function. This comprises inhibition
of thromboxane formation via inhibition of platelet phospholipase A2 and inhibition of (ox)LDL-C-mediated increases in platelet reactivity via the (ox)LDL-C
receptor (CD36). Furthermore, statins upregulate endothelial NO-synthase and improve
endothelial oxygen defense by inhibition of NADPH-oxidase. PCSK9 antibodies target
a serine protease (PCSK9), which promotes the degradation of the LDL-C receptor impacting
on LDL-C plasma levels and (ox)LDL-C-receptor-mediated signaling in platelets similar
to but more potent than statins.
These functionally synergistic actions are the basis for numerous interactions between
antiplatelet and these lipid-lowering drugs, which may, in summary, reduce the incidence
of atherothrombotic vascular events.
Keywords antiplatelet drugs - aspirin - PCSK9 - statins