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).
Inclusion Criteria:
High Lp(a) cohort: ≥ 125 nmol/L (approximately ≥ 75th percentile) Low Lp(a) comparator cohort (if applicable): < 25-30 nmol/L
Exclusion Criteria:
History of aspirin-induced asthma, severe NSAID intolerance, or anaphylactic reaction to salicylates.
Active peptic ulcer disease or clinically significant gastrointestinal bleeding within the past 6 months.
- Concomitant medications and interference with platelet function Current use of dual antiplatelet therapy (DAPT), oral anticoagulants (e.g., DOACs, vitamin K antagonists), or other potent antithrombotic agents that cannot be safely interrupted.
Use of non-steroidal anti-inflammatory drugs (NSAIDs) within 7 days prior to study entry (unless discontinued per protocol).
Use of P2Y12 inhibitors or aspirin within an insufficient washout period. - Clinical conditions Severe hepatic impairment (ALT/AST > 3× ULN) or severe renal impairment (eGFR < 30 mL/min/1.73 m²).
Active malignancy requiring systemic chemotherapy. Known hematologic disorder affecting platelet function or coagulation. Acute infection or inflammatory condition likely to affect platelet function.
- Other exclusions Pregnancy or breastfeeding. Participation in another interventional clinical trial within the last 30 days or 5 half-lives of the investigational product, whichever is longer.
Any condition that, in the opinion of the investigator, would interfere with study participation, compliance, or interpretation of results.
Kapka.Miteva@unige.ch+41 22 379 4648
Participants receive aspirin 100 mg once daily for 14 days, followed by a 14-day washout period, then clopidogrel 75 mg once daily for 14 days. Platelet function is assessed at baseline and after each treatment period.
Participants receive clopidogrel 75 mg once daily for 14 days, followed by a 14-day washout period, then aspirin 100 mg once daily for 14 days. Platelet function is assessed at baseline and after each treatment period.
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