Aspirin may benefit older individuals with elevated lipoprotein(a) [Lp(a)] genotypes for high-risk primary prevention of cardiovascular disease events, according to a study published Sept. 26 in JACC.

Paul Lacaze, PhD, et al., analyzed 12,815 genotyped individuals ≥70 years of age, of European ancestry, and without prior cardiovascular disease events who were enrolled in the ASPREE trial – a randomized, double-blind, placebo-controlled trial investigating the effect of daily 100 mg aspirin with a primary endpoint of disability-free survival over a median follow-up of 4.7 years.

Lp(a)-associated genotypes were defined using rs3798220-C carrier status; of the participants, 406 (3.2%) were carriers of rs3798220-C. The interaction between genotypes and aspirin allocation was tested in Cox proportional hazards models for incidence of major adverse cardiovascular events (MACE) and clinically significant bleeding. The endpoints of MACE include fatal coronary heart disease (excluding death from heart failure), nonfatal myocardial infarction, or fatal or nonfatal ischemic stroke, and clinically significant bleeding included major hemorrhage and intracranial bleeding. The associations in the aspirin and placebo arms of the trial were examined separately. 

Results showed that 435 MACE occurred, with an interaction observed between rs3798220-C and aspirin allocation (p=0.049). rs3798220-C carrier 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). 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 for all patients. In the rs3798220-C subgroup, aspirin reduced MACE by 11.4 and 3.3 events per 1,000 person-years, without significantly increased bleeding risk.

The authors conclude that “aspirin is a widely available, well tolerated, and low-cost therapeutic option and could play an important role in reducing Lp(a)-mediated [cardiovascular disease] risk” and that even though the benefits outweigh harm related to major bleeding, it should be balanced based on bleeding risks. 

In an accompanying editorial comment, Ana Devesa, MD; Borja Ibanez, MD; and Valentin Fuster, MD, PhD, MACC, notes the researchers should be “congratulated for a study of very high clinical relevance that represents a first indication for primary prevention for patients at high cardiovascular risk.” They add that moving forward, “the next steps in clinical practice should be defined, and there are still questions to be answered. Will every patient benefit from antithrombotic therapies? Should all patients who have elevated Lp(a) levels be treated with aspirin?”

Clinical Topics: Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, Vascular Medicine, Advanced Lipid Testing, Lipid Metabolism, Acute Heart Failure

Keywords: Heart Failure, Heart Disease Risk Factors, Coronary Disease, Genotype, Myocardial Infarction, Lipoprotein(a), Hemorrhage, Primary Prevention, Aspirin, Risk Factors, Ischemic Stroke, Follow-Up Studies, Proportional Hazards Models, Incidence, Fibrinolytic Agents, Cardiovascular Diseases

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