The goal of LDL-c management is to reduce long-term CVD risk. Statins form the foundation of lipid-lowering therapy, but more ammunition is needed to attain LDL-c goals in all patients. This series of 3 presentations discusses current and evolving therapeutic LDL-c lowering options.

In an ORION-11 substudy, inclisiran reduced LDL-c, non-HDL-c and apoB levels in a subgroup of high-risk patients with elevated LDL-c but without prior CV events receiving maximally tolerated statin therapy.

A pooled analysis of ORION-9, -10 and -11 offers early insights into the potential of inclisiran to lower CV risk in high-risk patients with elevated LDL-c levels, while results of dedicated CV outcomes trials are awaited.

AHA 2022 High CV risk patients in ORION-1 were invited to participate in open-label extension study with inclisiran -the ORION-3 study. What is the 4-year long-term efficacy and safety of inclisiran in these patients?

AHA 2022 The phase 2 OCEAN(a)-DOSE study showed that olpasiran dosed 75 mg or higher every 12 weeks reduces Lp(a) by >95% in patients with elevated Lp(a) and established ASCVD.

The Journal of the American College of Cardiology has published the 2022 ACC Expert Consensus Decision Pathway on the Role of Nonstatin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk.

Where do novel therapies targeting the PCSK9 pathway might fit in with regard to the lipid management paradigm? Ann Marie Navar gives an overview on current and future therapies.

Prof. Ray explains why therapy for LDL-c lowering in very high-risk patients should become like BP-combination therapy.

There have been no direct comparative studies of inclisiran, evolocumab, alirocumab, bempedoic acid, and ezetimibe in patients with hypercholesterolemia and increased cardiovascular risk receiving maximal tolerated statin therapy. A network meta-analysis may provide further insight.

ACC 2022 A post hoc pooled analysis from the ORION-10 and ORION-11 trials showed that inclisiran, compared with placebo, in addition to statin and/or ezetimibe provided effective and sustained LDL-c lowering in patients with prior MI.

ACC 2022 A phase 1 study showed that a siRNA targeting LPA mRNA reduced Lp(a) up to 98%. “It is an early study, this has got a long way to go, but we are optimistic that we are beginning an era where we are going to be able to treat this disorder”, Nissen said.

ACC 2022 A phase 1 single ascending dose study showed that subcutaneous injection of SLN360, an siRNA targeting mRNA for the LPA gene, lowered Lp(a) up to 98% in adults with elevated Lp(a) levels.