Four experts will provide an Update on Lipid-Lowering Drugs during the Virtual 80th Scientific Sessions. The two-hour symposium will begin at 2:15 p.m. CT Sunday, June 14.
Connie B. Newman, MD, FACP, FAHA, FAMWA, Adjunct Professor in the Robert I. Grossman School of Medicine at New York University Langone Health, will open the symposium with an analysis of how to diagnose, avoid, and treat the side effects of statin therapy. Following Dr. Newman’s presentation, three experts will review the science behind specific lipid-lowering agents.
Omega-3 Fatty Acids
Deepak L. Bhatt, MD, MPH, FACC, FAHA, FSCAI, FESC, Executive Director of Interventional Cardiovascular Programs at Brigham and Women’s Hospital and Professor at Harvard Medical School, will review results from Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (REDUCE-IT) first reported in 2019.
Results from REDUCE-IT showed a 25% reduction in first ischemic events and an overall 30% reduction in important cardiovascular events with icosapent ethyl, a prescription omega-3 fatty acid, versus placebo. This included a statistically significant 20% reduction in death from cardiovascular causes. Dr. Bhatt called this the “most significant development” in cardiovascular prevention since the introduction of statins more than two decades ago.
A subsequent analysis of outcomes in diabetes patients among the study’s 8,000-plus participants, all of whom had either established cardiovascular disease (CVD) or multiple risk factors for CVD, will be presented as a late-breaking abstract at the Scientific Sessions.
“It is an important subgroup,” said Dr. Bhatt, the abstract’s presenting author. “These are people who are often at higher risk of cardiovascular events, whether they are secondary prevention or primary prevention-type people with diabetes.”
Dr. Bhatt offered this advice to clinicians: “Be vigilant for patients with elevated triglycerides and realize for many of those patients there’s a new way to reduce their cardiovascular risk—and they are indeed at very high cardiovascular risk. Elevated triglycerides, in patients who are on statins especially, are an important marker of future cardiovascular risk. But now we can do something about that risk with icosapent ethyl.”
Jennifer G. Robinson, MD, MPH, will discuss the use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors to reduce low-density lipoprotein (LDL) cholesterol. While statins are the foundation of cardiovascular risk reduction therapy, even a maximum statin dose is not enough for some patients, and some patients have an intolerance to the drugs, she said.
“If the patient has an LDL over 100 mg/dl despite maximally tolerated statin therapy, then that patient probably would benefit from adding a PCSK9 inhibitor to reduce heart attack, stroke, and death more than they would perhaps from some other drugs,” Dr. Robinson said. “Patients with LDL over 100 mg/dl receive the most cardiovascular and mortality reduction from further LDL lowering.”
PCSK9 inhibitors are fairly expensive drugs in the cholesterol space, but not in the diabetes space, Dr. Robinson noted.
“They’re actually cheaper than some of the new diabetes drugs,” she said. “You’re going to get the most value from them by treating people with the highest cardiovascular risk, so that’s people with atherosclerotic cardiovascular disease and other high-risk factors like diabetes, familial hypercholesterolemia, chronic kidney disease, extensive polyvascular disease, and peripheral arterial disease, for example.”
John R. Guyton, MD, Professor of Medicine at Duke University School of Medicine and Editor of the Journal of Clinical Lipidology, will discuss a newly approved oral drug for lowering LDL cholesterol and its role in the long-term treatment of diabetes patients. Bempedoic acid has been approved for use on its own and in a combination tablet with ezetimibe.
“We think that the main use of this drug will be in statin-intolerant patients, and it will find some use also in patients whose LDL does not respond sufficiently to therapy with statins and ezetimibe,” Dr. Guyton said.
Similar to statins, bempedoic acid decreases the supply of the molecule Acetyl-CoA. The result is a decrease in LDL as well as high sensitivity C-reactive protein.
“There’s a really remarkable Mendelian randomization study related to the target for bempedoic acid, which is an enzyme called ATP citrate lyase,” Dr. Guyton explained. “Not only was LDL reduced in parallel with the genetic score, but you find a lipidomic signature of lipoprotein metabolism that’s almost identical to what you get with a genetic score for HMG-CoA reductase. HMG-CoA reductase is the target for statins, of course.”
While bempedoic acid has characteristics that appear to make it favorable for patients with type 2 diabetes, Dr. Guyton said it is too soon to predict how it will perform in patients with type 1 diabetes.
A cardiovascular outcomes trial of bempedoic acid is underway and should conclude in 2022.