Impact of PCSK9 Inhibitors on Lipoprotein(a) Levels: A Multi-Center Study

Aims With no currently available targeted therapies for lipoprotein(a) [Lp(a)] lowering, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) may be an option for management of increased cardiovascular risk in individuals with elevated Lp(a). However, Lp(a) lowering with PCSK9i is variable. We aimed to evaluate the real-world change in Lp(a) and predictors of response. Methods Using data from the University of California Health Data Warehouse, we conducted a multi-center retrospective study among adults prescribed PCSK9i therapy with available Lp(a) measurement before and after prescription. We evaluated change in Lp(a) compared to baseline and evaluated potential predictors of Lp(a) reduction using multivariable linear regression, including among patients with multiple serial Lp(a) measurements. Results Among 453 included individuals, PCSK9i use was associated with a median 17.3 [IQR 35.3, 0.0]% and 11.3 [31.7, 0.0] mg/dL reduction in Lp(a) overall. Among those with Lp(a) >50 mg/dL, a 17.7 [33.6, 0.0]% and 19.2 [42.0, 0.0] mg/dL reduction was observed. Higher baseline Lp(a) level (β -0.31, p<0.001) was a significant predictor of greater Lp(a) reduction, while female sex was associated with less reduction (β 9.28, p=0.02). Results were consistent across Lp(a) assay types and by PCSK9i type and sustained in those with serial Lp(a) measurements (n=274). In contrast, in a control group of 6750 individuals, a median change of 0.00 [-2.00, 3.00] mg/dL in Lp(a) was noted in serial measurements. Conclusions PCSK9i are associated with modest Lp(a) lowering of approximately 17% in real-world clinical practice, with a consistent percent reduction by baseline Lp(a) level, PCSK9i type and Lp(a) assay type. Predictors of Lp(a) reduction include baseline Lp(a) level and sex without significant variation by age, race/ethnicity or other evaluated comorbidities.