The Lp(a)-PLAT Study is designed to close a critical evidence gap in cardiovascular prevention for the roughly 20% of the population who carry genetically determined elevations in lipoprotein(a) - a recognised pro-thrombotic and pro-atherosclerotic risk factor. Its objective is to delineate the pro-thrombotic platelet phenotype driven by high Lp(a) levels and to evaluate, through pharmacodynamic comparison, how two standard-of-care antiplatelet strategies - clopidogrel, a P2Y12 ADP-receptor inhibitor, and aspirin, a COX-1 inhibitor - differ in their capacity to attenuate this platelet hyperreactivity.
This study will provide the first head-to-head mechanistic comparison of clopidogrel versus aspirin on platelet reactivity in patients with elevated plasma levels of Lp(a).
Age ≥ 18 years at the time of informed consent.
Ability to provide written informed consent in accordance with Swiss Human Research Act (HRA) and ICH-GCP.
Clinically stable at the time of inclusion, with no acute cardiovascular event within the previous 3 months.
Willingness and ability to comply with all study procedures, including blood sampling and study medication intake.
Cardiovascular and bleeding-related conditions Active bleeding or known bleeding disorder. History of hemorrhagic stroke or intracranial hemorrhage. High risk of bleeding as judged by the investigator. Platelet count < 100 × 10⁹/L at screening. Known platelet function disorder.
Contraindications to study medications Known hypersensitivity or contraindication to aspirin (acetylsalicylic acid) or clopidogrel.
Crossover
Aspirin
DrugAspirin 100 mg administered orally once daily for 14 consecutive days during one treatment period of the randomized crossover study. Participants receive aspirin either during Period 1 or Period 2 depending on the randomized treatment sequence. A 14-day washout period separates the two treatment periods.
Clopidogrel
DrugClopidogrel 75 mg administered orally once daily for 14 consecutive days during one treatment period of the randomized crossover study. Participants receive clopidogrel either during Period 1 or Period 2 depending on the randomized treatment sequence. A 14-day washout period separates the two treatment periods.
Change in collagen-induced platelet aggregation after aspirin versus clopidogrel treatment
Within-participant change from baseline in collagen-induced platelet aggregation measured by light transmission aggregometry (LTA) after 14 days of aspirin 100 mg once daily compared with 14 days of clopidogrel 75 mg once daily in the randomized crossover design.
Change in soluble platelet activation biomarkers after aspirin versus clopidogrel treatment
Within-participant change from baseline in soluble platelet activation biomarkers (including soluble P-selectin/CD62P, soluble CD40 ligand \[sCD40L\], platelet factor 4 \[PF4\], and related biomarkers) following 14 days of aspirin 100 mg once daily compared with 14 days of clopidogrel 75 mg once daily.
Agonist-specific platelet aggregation
Change from baseline in platelet aggregation measured by light transmission aggregometry following stimulation with arachidonic acid, ADP, and TRAP-6 after each treatment period.
Platelet surface activation markers
Change from baseline in platelet surface expression of CD62P (P-selectin) and activated GPIIb/IIIa measured by flow cytometry following aspirin and clopidogrel treatment.
Biochemical verification of aspirin pharmacodynamic effect
Serum thromboxane B2 (TxB2) concentration measured to verify cyclooxygenase-1 inhibition during aspirin treatment.
Biochemical verification of clopidogrel pharmacodynamic effect
Vasodilator-stimulated phosphoprotein (VASP) platelet reactivity index (PRI) measured to verify P2Y12 receptor inhibition during clopidogrel treatment.
Identification of candidate biomarkers associated with lipoprotein(a)-related platelet hyperreactivity
Exploratory identification of circulating protein biomarkers associated with platelet hyperreactivity and pharmacodynamic response to aspirin and clopidogrel using Olink® proteomic analysis. Results are hypothesis-generating only.
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François MACH
Lead sponsor
University Hospital, Geneva
Sponsor institution
University Hospital, Geneva
Collaborator
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