Author + information
- Blair Edmiston,
- Nathan Brooks,
- Jessica Minnier,
- Cezary Wojcik,
- Barton P. Duell,
- Jonathan Q. Purnell,
- Tina Kaufman,
- Hagai Tavori,
- Sergio Fazio and
- Michael Shapiro
Background: Clinical trials of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) demonstrate an unanticipated but significant lipoprotein(a) [Lp(a)] lowering effect of up to 30%. While the 50-60% reduction in low density lipoprotein (LDL)-cholesterol (LDL-C) achieved by PCSK9i is mediated through its effect on LDL receptor (LDLR) preservation, the mechanism for Lp(a) lowering is unknown. Some hypothesize that the PCSK9i-induced Lp(a) reduction is also due to enhanced clearance through the LDLR. If that is the case, the Lp(a) response to PCSK9i should be proportional to the LDL-C response.
Methods: Consecutive patients who received PCSK9i treatment in our Center for Preventive Cardiology were included if they had: a) at least one measurement of LDL-C and Lp(a) prior to and after initiation of PCSK9i; b) baseline Lp(a) >10 mg/dL; and c) continued adherence to PCSK9i therapy. They were excluded if: a) they were undergoing LDL apheresis; b) pre- or post-PCSK9i LDL-C or Lp(a) lab values were censored; or c) subjects discontinued other lipid modifying therapies. In total, 103 subjects were identified as taking a PCSK9i and 26 met all inclusion and exclusion criteria. Concordant response to therapy was defined as an LDL-C reduction >35% and an Lp(a) reduction >10%.
Results: Average percent reductions in LDL-C and Lp(a) were 52.8% (95% CI 47.0 – 58.6) and 20.2% (12.2 – 28.1). The corresponding average absolute LDL-C and Lp(a) reductions were 88.1 mg/dL (70.7 – 105.5) and 14.6 mg/dL (8.4 – 20.9). The correlation between % LDL and % Lp(a) reduction was moderate, with a Spearman's correlation of 0.56 (p<0.01). All subjects except for one had an appropriate LDL-C response to therapy. Only 16 of the 26 (62%; 95% CI 41-82%) subjects had a significant Lp(a) response. While some subjects demonstrated negligible Lp(a) reduction to PCSK9i, others demonstrated profound Lp(a) lowering (eg, >60%).
Conclusions: We demonstrate moderate correlation but large discordance (∼40%) in these two lipid fractions in response to PCSK9i. The results suggest that alternate pathways beyond the LDLR are responsible for Lp(a) lowering and indicate that PCSK9i have the potential to significantly lower Lp(a) in select patients.
Moderated Poster Contributions
Prevention Moderated Poster Theater, Poster Hall, Hall C
Friday, March 17, 2017, 11:45 a.m.-11:55 a.m.
Session Title: The PCSK9 Revolution: New Insights Into Evaluation and Treatment
Abstract Category: 32. Prevention: Clinical
Presentation Number: 1133M-17
- 2017 American College of Cardiology Foundation