PCSK9: the new lipid target in preventive cardiology?
Keep checking this site, as more presentations and webcasts related to the PACE Educational Programmes will be available in the near future.
As part of the ESC congress 2013, the PACE Foundation organised three EBAC Accredited Educational Programmes:
Via these EBAC-Accredited Educational Programmes, the PACE Foundation aims to help physicians to assimilate the proven findings of scientific research into the day-to-day practice of clinical medicine, aiming to improve outcomes in patients.
The first PACE symposium focused on the possible role of PCSK9 as the new lipid target in preventive cardiology. Prof. dr. John Kastelein (Amsterdam, The Netherlands) opened the session by giving an introduction on autosomal dominant hypercholesterolemia. These patients have a greatly increased cardiovascular risk. Mean age of parental death is 39.8 years old, which is still quite early for a disease that can be treated, as Prof. Kastelein remarked. Despite optimal accessibility to care, LDL-c targets are still not met in most of these patients. Therefore, more potent drugs to lower LDL-c levels are needed.
Monoclonal antibodies directed against PCSK9 seem promising in this respect, since their effect on LDL reduction appear to be additive to that of statins. Dr. Gilles Lambert (Nantes, France) therefore elaborated on mechanistic insights into a new therapeutic approach to lower LDL-c, namely by PCSK9 inhibition. He described the discovery of the PCSK9 gene and its role in the LDL-receptor metabolism, and its effects on LDL-c levels. Hopeful results with PCSK9 inhibition have been obtained in animal studies and the first studies in humans have also shown benefits. Dr. Lambert also showed data that demonstrate that PCSK9 inhibition will be effective both in patients with familial hypercholesterolemia (FH) and in non-FH patients, either alone or in combination with statins.
Dr. Evan E Stein (Cincinatti, OH, USA) zoomed in on the efficacy of monoclonal antibodies that target PCSK9. He discussed results that have been obtained in clinical trials thus far, which show that the PCSK9-antibodies cause very effective LDL-c reductions, with effects persisting for 2 weeks at the tested doses. Although a synergistic effect between PCSK9 inhibition and statin treatment was hoped for, this was not observed. Doubling or tripling the dose of concomitant statin treatment does increase the effective duration, but does not yield an additional LDL-c decrease, suggesting that all LDL-receptors have already been saturated at that point. Safety data confirm the encouraging results of PCSK9 inhibition.
Prof. dr. Henry Ginsberg (New York, NY, USA) concluded the satellite symposium with an overview of novel approaches to inhibit PCSK9 that are currently in development. He explained the biology of these agents and showed that available phase I and II results are promising with respect to efficacy and safety. The first phase III trials, including CVD outcome studies, are now underway, which will determine the role of PCKS9 inhibition in clinical practice.
The slides of these presentations will become available on this website:
- John Kastelein: Familial Hypercholesterolemia: Why are we not reaching goals in these patients?
- Gilles Lambert: PCSK9 inhibition: Mechanistic insights into a new therapeutic approach for the lowering of LDL-c
- Evan Stein: Monoclonal antibodies that target PCSK9: What the first clinical trial data are telling?
- Henry Ginsberg: The roadmap of PCSK9 inhibitors towards the clinic: An overview of current development programs & outcome studies