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Thromb Haemost 2023; 123(02): 166-176
DOI: 10.1055/s-0042-1758654
Theme Issue Article

Drug–Drug Interaction between Antiplatelet Therapy and Lipid-Lowering Agents (Statins and PCSK9 Inhibitors)

Karsten Schrör‡   *
1   Institut für Pharmakologie und Klinische Pharmakologie, Heinrich-Heine-Universität, Düsseldorf, Düsseldorf, Germany
,
Freek W. A. Verheugt 
2   Department of Cardiology, Onze Lieve Vrouwe Gasthuis (OLVG), Amsterdam, The Netherlands
,
Dietmar Trenk  ‡   *
3   Department Universitäts-Herzzentrum, Klinik für Kardiologie und Angiologie Bad Krozingen, Klinische Pharmakologie, Universitätsklinikum Freiburg, Bad Krozingen, Germany
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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

* Authors contributed equally to the manuscript (shared main authorship)




Publication History

Received: 01 March 2022

Accepted: 23 September 2022

Article published online:
15 December 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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