1. Aspirin for Primary Prevention of Cardiovascular Events in Relation to Lipoprotein(a) Genotypes
- Author
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Lacaze, Paul, Bakshi, Andrew, Riaz, Moeen, Polekhina, Galina, Owen, Alice, Bhatia, Harpreet S, Natarajan, Pradeep, Wolfe, Rory, Beilin, Lawrence, Nicholls, Stephen J, Watts, Gerald F, McNeil, John J, Tonkin, Andrew M, and Tsimikas, Sotirios
- Subjects
Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Clinical Research ,Cardiovascular ,Prevention ,Clinical Trials and Supportive Activities ,Patient Safety ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Good Health and Well Being ,Aged ,Aspirin ,Cardiovascular Diseases ,Genotype ,Humans ,Lipoprotein(a) ,Primary Prevention ,aspirin ,cardiovascular disease ,genetics ,lipoprotein(a) ,primary prevention ,Cardiorespiratory Medicine and Haematology ,Public Health and Health Services ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology - Abstract
BackgroundThe role of aspirin in reducing lipoprotein(a)-mediated atherothrombotic events in primary prevention is not established.ObjectivesThis study sought to assess whether low-dose aspirin benefits individuals with elevated plasma lipoprotein(a)-associated genotypes in the setting of primary prevention.MethodsThe study analyzed 12,815 genotyped individuals ≥70 years of age of European ancestry and without prior cardiovascular disease events enrolled in the ASPREE (ASPirin in Reducing Events in the Elderly) randomized controlled trial of 100 mg/d aspirin. We defined lipoprotein(a)-associated genotypes using rs3798220-C carrier status and quintiles of a lipoprotein(a) genomic risk score (LPA-GRS). We tested for interaction between genotypes and aspirin allocation in Cox proportional hazards models for incidence of major adverse cardiovascular events (MACE) and clinically significant bleeding. We also examined associations in the aspirin and placebo arms of the trial separately.ResultsDuring a median 4.7 years (IQR: 3.6-5.7 years) of follow-up, 435 MACE occurred, with an interaction observed between rs3798220-C and aspirin allocation (P = 0.049). rs3798220-C carrier status was associated with increased MACE risk in the placebo group (HR: 1.90; 95% CI: 1.11-3.24) but not in the aspirin group (HR: 0.54; 95% CI: 0.17-1.70). High LPA-GRS (vs low) was associated with increased MACE risk in the placebo group (HR: 1.70; 95% CI: 1.14-2.55), with risk attenuated in the aspirin group (HR: 1.41; 95% CI: 0.90-2.23), but the interaction was not statistically significant. In all participants, aspirin reduced MACE by 1.7 events per 1,000 person-years and increased clinically significant bleeding by 1.7 events per 1,000 person-years. However, in the rs3798220-C and high LPA-GRS subgroups, aspirin reduced MACE by 11.4 and 3.3 events per 1,000 person-years respectively, without significantly increased bleeding risk.ConclusionsAspirin may benefit older individuals with elevated lipoprotein(a) genotypes in primary prevention.
- Published
- 2022