In a large Danish contemporary general population study, low LDL-c due to PCSK9 genetic variation caused a lower CV mortality risk. Cancer and all-cause mortality were not altered by the gene variants.

EAS 2019 Prof. Evan Stein summarizes novel phase II data of a new 'small binding protein', consisting of adnectin and human albumin, which inhibits PCSK9. The results were such that a phase 3 trial has now started to further study the compound.

EAS 2019 Prof. Chapman lists the newest findings on the associations of Lp(a) levels, PCSK9 inhibitors and CV risk, based on new analyses of the FOURIER and ODYSSEY OUTCOMES trials.

A meta-analysis showed significantly elevated Lp(a) levels with statin therapy and a cell culture study demonstrated increased apo(a) production after statin treatment, which possibly contributes to the residual CV risk in subjects on statins.

EAS 2019 The pilot ORION-2 study shows that inclisiran, an siRNA that prevents production of PCSK9, yielded persistent lowering of LDL-c levels up to 6 months in 3 out of 4 hoFH patients.

EAS 2019 Four-weekly injection of recombinant fusion protein that binds PCSK9 yielded 77% reduction in LDL-c at 12 weeks, in patients with elevated LDL-c on statin therapy.

New data of the ORION-3 trial demonstrate that twice a year dosing of the siRNA directed at PCSK9 mRNA inclisiran gives sustained and safe lowering of LDL-C by more than 50 percent for up to 3 years, on top of LDL-c lowering therapies.

LDL-c levels vary greatly among pediatric patients with genetically defined hoFH, and overlap exists between the LDL-c levels and phenotypes of severe heFH and hoFH.

Identification of FH in ACS patients is crucial, as it has an impact on the clinical trajectory. Prof. Hovingh discusses how to classify these patients and their prognosis.

This series covers four topics that help cardiologists understand the role of PCSK9 in lipid metabolism and PCSK9 inhibitors as a novel strategy to reduce LDL-c. Member registration (free) is needed to enroll in this course

A prespecified analysis of the ODYSSEY OUTCOMES trial showed a higher incidence of MACE and death in ACS patients with polyvascular disease and alirocumab treatment resulted in a large absolute benefit in these patients.

Depending on individual patient characteristics, novel therapeutic approaches can reduce CV risk, particularly in patients at high CV risk. Prof. Landmesser expects that future guidelines will reflect these developments.