Adding Praluent (Alirocumab) To Statins Reduces LDL in High Cardiovascular Risk Diabetics

MedicalResearch.com Interview with:

Lawrence Leiter, M.D. MDCM, FRCPC, FACP, FACE, FAHA Chair of the ODYSSEY DM Steering Committee and Director of the Lipid Clinic at the Li Ka Shing Knowledge Institute St. Michael’s Hospital University of Toronto, Canada

Dr. Lawrence Leiter

Lawrence Leiter, M.D. MDCM, FRCPC, FACP FACE, FAHA
Chair of the ODYSSEY DM Steering Committee and
Director of the Lipid Clinic at the Li Ka Shing Knowledge Institute
St. Michael’s Hospital
University of Toronto, Canada

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The ODYSSEY DM-INSULIN trial was a randomized, double-blind, placebo-controlled, multicenter study that evaluated alirocumab (Praluent) in 517 patients with insulin treated type 1 and type 2 diabetes with high cardiovascular (CV) risk and hypercholesterolemia despite maximally tolerated dose (MTD) statins. The primary endpoint was percent change in calculated LDL-C from baseline to week 24.

Alirocumab 75 mg every two weeks was added to MTD statins, with the dose increased at week 12 to 150 mg every two weeks if the LDL-C at week 8 was greater than or equal to 70 mg/dL. In fact, only about 20% of the alirocumab treated participants required the higher dose.

Results of the type 2 diabetes study population (n=441) showed that the addition of alirocumab to MTD statin therapy, reduced LDL-C by 48.2 percent from baseline compared to a 0.8 percent increase for placebo. The mean difference between the two treatment arms was -49 percent (p<0.0001). Treatment with alirocumab also improved the overall lipid profile. Furthermore, no new safety issues were identified.

There is a large unmet need for improving cholesterol lowering in patients with diabetes. Despite current standard of care, nearly 70 percent of people age 65 or older with diabetes die from some form of heart disease; and 16 percent die of stroke. Additionally, in spite of current standard of care, many people with diabetes continue to have persistent lipid abnormalities resulting in high residual CV risk.

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PCSK9 Inhibition with Alirocumab Increases Removal of LDL Cholesterol

MedicalResearch.com Interview with:
Henry N. Ginsberg, MD

Irving Institute for Clinical and Translational Research
Columbia University
Columbia College of Physicians and Surgeons
New York, NY

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Previous studies in mice and cells have identified increased hepatic low density lipoprotein (LDL) receptors as the basis for LDL lowering by PCSK9 inhibitors, but there have been no human studies characterizing the effects of PCSK9 inhibitors on lipoprotein metabolism, particularly effects on very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL) or LDL metabolism.

This study in 18 healthy subjects, found that alirocumab decreased the number of IDL and LDL particles in the circulation, and their associated cholesterol and apoB levels by increasing efficiency of the clearance of IDL and LDL. There were not effects on VLDL metabolism. The increased clearance of IDL meant that less LDL was produced from IDL, which is the precursor of LDL. Thus, the dramatic reductions in LDL cholesterol resulted from both less LDL being produced and more efficient clearance of LDL. These results are consistent with increases in LDL receptors available to clear IDL and LDL from blood during PCSK9 inhibition.

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