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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 | |
Novel Treatment Lowers LDL Cholesterol |
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 | |
Novel Treatment Lowers LDL Cholesterol |
Take-home Points
• When PCSK9 is inhibited, LDL-receptors on hepatocytes are increased and more LDL-C is taken up from the blood, reducing circulating concentrations.
• Phase II studies with an injectable monoclonal antibody inhibitor of PCSK9 have resulted in a 60% to 80% decrease in LDL-C, over and above what is achieved with background statin therapy.
• Studies are underway 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 who are already on a statin or unable to tolerate a statin and will likely result in more patients achieving LDL-C targets in primary and secondary prevention. Large Phase III studies are currently underway to study this drug with respect to cardiac events and outcomes.
