Key result
In vitro GPVI-Fc plus ASA and ticagrelor inhibits plaque-induced platelet aggregation ~93% without increasing closure time.
Why the study?
The efficiency of current dual antiplatelet therapy might be improved by combining it with a glycoprotein VI-targeting strategy without increasing bleeding risk.
Does recombinant GPVI-Fc added to single or dual antiplatelet therapy reduce plaque-induced platelet aggregation in vitro?
Does recombinant GPVI-Fc added to single or dual antiplatelet therapy reduce plaque-induced platelet aggregation in vitro?
Adding recombinant GPVI-Fc to standard antiplatelet therapy significantly enhances inhibition of plaque-induced platelet aggregation in vitro without prolonging closure time, offering a potential targeted anti-atherothrombotic approach.
Answers are grounded in this paper and cite their sources.
Hypothesis-generating for GPVI-Fc adjunctive therapy; does not support clinical use or trials.
Summary The efficiency of current dual antiplatelet therapy might be further improved by its combination with a glycoprotein (GP) VI-targeting strategy without increasing bleeding. GPVI-Fc, a recombinant dimeric fusion protein binding to plaque collagen and concealing binding sites for platelet GPVI, acts as a lesion-focused antiplatelet drug, and does not increase bleeding in vivo. We investigated, whether GPVI-Fc added in vitro on top of acetylsalicylic acid (ASA), the P2Y12 antagonist ticagrelor, and the fibrinogen receptor antagonist abciximab alone or in combination would increase inhibition of platelet activation by atherosclerotic plaque. Under static conditions, GPVI-Fc inhibited plaque-induced platelet aggregation by 53%, and increased platelet inhibition by ASA (51%) and ticagrelor (64%) to 66% and 80%, respectively. Under arterial flow, GPVI-Fc inhibited plaque-induced platelet aggregation by 57%, and significantly increased platelet inhibition by ASA (28%) and ticagrelor (47%) to about 81% each. The triple combination of GPVI-Fc, ASA and ticagrelor achieved almost complete inhibition of plaque-induced platelet aggregation (93%). GPVI-Fc alone or in combination with ASA or ticagrelor did not increase closure time measured by the platelet function analyzer (PFA)-200. GPVI-Fc added on top of abciximab, a clinically used anti-fibrinogen receptor antibody which blocks platelet aggregation, strongly inhibited total (81%) and stable (89%) platelet adhesion. We conclude that GPVI-Fc added on top of single or dual antiplatelet therapy with ASA and/or a P2Y12 antagonist is likely to improve anti-atherothrombotic protection without increasing bleeding risk. In contrast, the strong inhibition of platelet adhesion by GPVI-Fc in combination with GPIIb/IIIa inhibitors could be harmful. Note: The review process for this manuscript was fully handled by Gregory Y. H. Lip, Editor in Chief. Supplementary Material to this article is available at www.thrombosis-online.com.
No takes yet. Share an insight, caveat, or question.
Munoz et al. (2017) studied Atherothrombosis. Recombinant GPVI-Fc vs. Single or dual antiplatelet therapy alone (ASA, ticagrelor, abciximab) was evaluated on Plaque-induced platelet aggregation. In vitro, adding recombinant GPVI-Fc to ASA and ticagrelor achieved 93% inhibition of plaque-induced platelet aggregation without increasing closure time.
Synapse has enriched 10 related papers. Consider them for comparative context: