Lipoprotein (a) assay methods similarly predict MACE reduction with PCSK9 inhibitor Alirocumab: Study

The study stated, “With caveats of a modest number of MACE for analysis, moderately elevated Lp(a) levels, and intra-patient variability in serial values, three Lp(a) assay methods appeared comparably predictive of ALI MACE reduction, independent of reduction in LDL cholesterol,”

The findings were published online in the European Journal of Preventive Cardiology on March 19, 2024.

Baseline (BL) lipoprotein (a) concentrations are similarly related to cardiovascular (CV) risk when measured in either molar units or mass by immunoassay (IA). Because of Lp(a) isoform variation in mass, there may be differences between Lp(a) measurement methods in terms of relating change to risk reduction.

Against the above background, Michael Szarek, Division of Cardiology, University of Colorado School of Medicine, Aurora, CO, USA, and colleagues determined whether the reduction in MACE by PCSK9 inhibitor alirocumab has a similar relationship to the reduction in Lp (a) concentration as measured by three different methods.

Lipoprotein (a) was measured by IA-molar (Roche), IA-mass (Siemens), and mass spectrometry (MS)-molar assays at baseline and month 4 (M4) in a subgroup of patients in the ODYSSEY OUTCOMES trial. The trial compared PCSK9 inhibitor ALI with placebo in patients with recent acute coronary syndrome.

Changes in Lp(a) from baseline to M4 were related to subsequent risk of MACE (nonfatal myocardial infarction, coronary heart disease death, unstable angina hospitalization, or fatal + nonfatal ischemic stroke) in the ALI group. Proportional hazard models were adjusted for baseline Lp(a), baseline LDL-C and its change from BL to M4, and other patient characteristics. Hazard ratios (HR) were calculated for the median change of each Lp(a) assay.

The study led to the following findings:

• Among 5500 patients randomized to ALI with available data from all 3 Lp(a) assays, 443 experienced a subsequent MACE.
• Changes in Lp(a) IA-mass and MS-molar concentration were significantly related to reduced MACE risk, while a change in IA-molar concentration was marginally significant; associations were more evident with coronary heart disease death + nonfatal MI.
• MACE HRs for median change were similar across tests.

In conclusion, despite the relatively low number of MACE available for analysis, only moderately elevated lipoprotein levels, and intra-patient variability in serial value, the researchers showed that each of the 3 Lp(a) assay methods was similarly predictive of modest MACE reductions with alirocumab treatment.

“Greater clinical benefits might be observed, with the emergence of new potent Lp(a) lowering agents,” the researchers wrote.

Reference:

Szarek, M., Reijnders, E., Steg, P. G., Jukema, J. W., Schwertfeger, M., Bhatt, D. L., Bittner, V. A., Diaz, R., Fazio, S., Garon, G., Goodman, S. G., Harrington, R. A., White, H. D., Zeiher, A. M., Cobbaert, C., & Schwartz, G. G. Comparison of Change in Lipoprotein(a) Mass and Molar Concentrations by Alirocumab and Risk of Subsequent Cardiovascular Events in ODYSSEY OUTCOMES. European Journal of Preventive Cardiology. https://doi.org/10.1093/eurjpc/zwae110