Aspirin okay for primary prevention among elderly with elevated lipoprotein(a)

Older people with increased lipoprotein(a) genotypes may benefit from aspirin against cardiovascular events, says an article published in the Journal of American College of Cardiology.

Aspirin's potential contribution to the primary prevention of lipoprotein(a)-mediated atherothrombotic events is unknown. In order to determine if low-dose aspirin is advantageous for those with increased plasma lipoprotein(a)-associated genotypes in the context of primary prevention, Paul Lacaze and colleagues undertook this study.

The study looked at 12,815 genotyped people over the age of 70 who were of European ancestry and had no prior cardiovascular disease events and were participating in the ASPREE (ASPirin in Reducing Events in the Elderly) randomized controlled trial of 100 mg/d aspirin. Lipoprotein(a)-associated genotypes were determined using rs3798220-C carrier status and quintiles of a lipoprotein(a) genomic risk score (LPA-GRS).

The key findings of this study were:

1. 435 MACE occurred across a median of 4.7 years (IQR: 3.6-5.7 years) of follow-up, with an interaction detected between rs3798220-C and aspirin allocation (P = 0.049).

2. The presence of rs3798220-C was related with an elevated risk of MACE in the placebo group but not in the aspirin group.

3. High LPA-GRS (vs. low) was related with an increased risk of MACE in the placebo group, whereas the risk was reduced in the aspirin group, although the interaction was not statistically significant.

4. Aspirin decreased MACE by 1.7 occurrences per 1,000 person-years while increasing clinically severe bleeding by 1.7 events per 1,000 person-years in all subjects.

5. Aspirin, on the other hand, decreased MACE by 11.4 and 3.3 occurrences per 1,000 person-years in the rs3798220-C and high LPA-GRS categories, respectively, without significantly increasing bleeding risk.

In conclusion, when comparing carriers to noncarriers, the investigators discovered a substantial interaction with aspirin. When comparing high Lp(a) genetic risk score quintiles to low quintiles, this interaction was not significant. This might imply that the existence of the genetic variation suggests a distinct risk that does not entirely overlap with that imparted by higher Lp(a) levels in the blood.

Reference:

Lacaze, P., Bakshi, A., Riaz, M., Polekhina, G., Owen, A., Bhatia, H. S., Natarajan, P., Wolfe, R., Beilin, L., Nicholls, S. J., Watts, G. F., McNeil, J. J., Tonkin, A. M., & Tsimikas, S. (2022). Aspirin for Primary Prevention of Cardiovascular Events in Relation to Lipoprotein(a) Genotypes. In Journal of the American College of Cardiology (Vol. 80, Issue 14, pp. 1287–1298). Elsevier BV. https://doi.org/10.1016/j.jacc.2022.07.027.