There’s a new way to lower LDL cholesterol levels-by approximately 60% to 80%. Studies unveiled at the 2012 ACC meeting found that an injectable monoclonal antibody, when added to statin therapy cuts LDL cholesterol levels far in excess of what can be achieved with statin therapy alone. Drs Christopher Cannon and Payal Kohli discuss.
There’s a new way to lower LDL cholesterol levels-by approximately 60% to 80%. Studies unveiled at the 2012 American College of Cardiology Meeting in Chicago shed light on this novel treatment-an injectable monoclonal antibody that when added to statin therapy cuts LDL cholesterol levels far in excess of what can be achieved with statin therapy alone. Results from Phase I and Phase II studies were recently published in The New England Journal of Medicine and the Journal of the American College of Cardiology and are quite promising.
This new drug suppresses the function of the PCSK9 gene which, when overexpressed, has been shown to decrease the number of LDL receptors expressed on liver cells. Gain-of-function mutations in this gene have been linked to familial hypercholesterolemia while loss-of-function mutations are associated with low LDL cholesterol levels and low prevalence of coronary heart disease events.
Is this breakthrough as promising as it sounds? Which patients stand to benefit most from the new therapy? And how might an agent with such therapeutic power affect lipid management in primary care practice?
Here to put this issue into perspective are Drs Christopher Cannon and Payal Kohli. Dr Cannon, a senior investigator with the TIMI Study Group, is editor in chief of Cardiosource Science and Quality. He is also Professor of Medicine at Harvard Medical School and Associate Physician in the Cardiovascular Division of Brigham and Women’s Hospital in Boston. Dr Kohli graduated from Harvard Medical School and completed her internal medicine training in Boston and is scheduled to start her fellowship in cardiovascular medicine at the University of California San Francisco in June 2012.
Novel Treatment Lowers LDL Cholesterol
• PCSK9 is a secreted protein involved in targeting LDL receptors for destruction.
• When PCSK9 is inhibited, LDL receptors on hepatocytes are increased and more LDL cholesterol is taken up from the blood, reducing circulating concentrations.
• Phase 2 studies with an injectable monoclonal antibody inhibitor of PCSK9 have resulted in a 60% to 80% decrease in LDL cholesterol levels, over and above what is achieved with background statin therapy.
• Studies are under way in many types of cohorts, including statin-intolerant patients and patients with familial hypercholesterolemia.
• This novel drug offers an exciting agent for further reducing LDL cholesterol levels in patients who are already taking a statin or who are unable to tolerate a statin and will likely result in more patients achieving LDL cholesterol targets in primary and secondary prevention. Large phase 3 studies are currently under way to study this drug with respect to cardiac events and outcomes.