A new “extreme risk” category for cardiovascular disease—and a new target threshold of less than 55 mg/dL for low-density lipoprotein cholesterol (LDL-C) for those in this category — is part of the 2017 American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology practice guidelines1 for management of dyslipidemia (aka high cholesterol) and prevention of cardiovascular disease, says Paul Jellinger, MD, an endocrinologist and chair of the guidelines. He presented the guidelines at the AACE 2017 annual meeting in Austin, Texas last week, Friday May 4th.
Those who fall into extreme risk category include those who have progressive atherosclerotic cardiovascular disease (ASCVD), including unstable angina even after achieving an LDL-C of under 70 mg/dL; patients with established cardiovascular disease who also have diabetes, chronic kidney disease stage 3 or 4 or familial hypercholesterolemia (high cholesterol in one or both parents); or a personal history of premature ASCVD (heart disease in men under age 55 or under age 65 in women). “Roughly 10 to 15 percent of the population probably fall into the extreme risk category, and for the diabetic population it’s likely higher,” says Dr. Jellinger.
“Until now, people with a very high risk had an LDL-C target of 70 mg/dL or less, but we now have a subgroup of patients who have a need for an LDL under 55 mg/dL, and more patients than one might think belong in that category,” says Dr. Jellinger, who is also professor of clinical medicine at the University of Miami. “People in this group have a significantly increased chance of having a major or lethal ASCVD event over the next 4 to 5 years,” he says.
(Adults with diabetes are two to four times more likely to die from heart disease than adults without diabetes, according to the American Heart Association, and people with diabetes develop heart disease at a younger age than those without diabetes, according to the Centers for Disease Control and Prevention.)
Dyslipidemia — primarily elevated LDL cholesterol — is a primary, major risk factor for ASCVD. “We know from randomized controlled studies, such as IMPROVE-IT, 2 that people with heart disease and diabetes or other risk factors fare better when their LDL-C was lowered to 53 mg/dL on combination simvastatin and ezetimibe,” says Dr. Jellinger, adding that the FOURIER trial 3 validated lowering LDL-C to less than 55 mg/dL utilizing a PCSK9 inhibitor was advantageous. “Studies have shown that for every level of LDL-C, lowering the LDL-C further reduces events,” he says. (Such “events” include a myocardial infarction, stroke or death from a cardiovascular cause.)
Some heart health organizations, such as the American College of Cardiologists (ACC) and American Heart Association (AHA), do not include treating patients to LDL-C target numbers in their current practice guidelines. “There isn’t anything wrong with treating patients to a target LDL, but when the ACC and AHA convened for their 2013 guidelines,4 the evidence didn’t support setting goals,” says Robert Eckel, MD, past president of the American Heart Association and professor of medicine at University of Colorado Anschutz Medical Campus in Denver. “The studies certainly show that lowering LDL-C reduces one’s risk of heart disease, but those studies didn’t look at treating to a specific target number, so we couldn’t recommend it,” he tells EndocrineWeb.com, adding that in reality, doctors—including himself— often do treat using target numbers because it can be helpful to know what the goal is.
Still, many practicing cardiologists and endocrinologists find the new extreme risk category and lower target LDL numbers a positive. “It’s a wonderful step in the right direction,” says Seth Baum, MD, president of the American Society for Preventive Cardiology and Founder/Chief Medical Officer, Excel Medical Clinical Trials in Boca Raton, Florida. “Every single European guideline has an LDL target, and many of us continue to use specific numbers to treat patients,” he tells EndocrineWeb.com. “Not only is aggressively lowering LDL for these patients important, but treating patients as early as possible is key to improving lifespan,” says Dr. Baum.
The standard treatment for lowering LDL is to use the maximally tolerated level of a statin drug. However, not everyone will be able to get their LDL down to very low levels with statins alone, and not everyone tolerates a statin. “It’s usually statins plus something else, such as ezetimibe or—if more aggressive lowering is needed—a new PCSK9 inhibitor drug, either alirocumab or evolocumab” says Dr. Baum, who adds that even when PCSK9 inhibitor is indicated, insurers usually make it difficult to get approval. “It’s a huge problem, up to 80% of initial claims are rejected, sometimes higher, according to research. Doctors are trying to help patients get their LDL down—something we know reduces their risk of heart attack and stroke—and patients can’t get the drugs covered,” says Dr. Baum, who has published research on the topic, organized conferences on the issue and created an open-access form letter 5 for prior authorization and appeals for clinicians looking to prescribe PCSK9i drugs on label. Experts suspect that insurance companies are primarily denying claims based on the cost of the new drugs, which were approved in 2015—the list price is around $14,000 per year,6 though the negotiated price is often lower. “The true cost of the drug in the first year after approval was a small fraction of the predicted cost, about 1.2 percent,” he says.
Dr. Paul S. Jellinger reports that he has received speaker honoraria from BI-Lilly, AstraZeneca, Novo Nordisk, Amgen, and Merck.
Dr. Robert Eckel reports he has served as a witness in a trial for Sanofi-Aventis.
Dr. Seth Baum reports he has served on the scientific advisory boards of Amgen, Regeneron, Sanofi, Akcea, Ionis; has been a speaker for Amgen, Merck, BI, Lilly; and has done research for Regeneron, Amgen, Esperion, BI, Regenex, Madrigal, Gemphire.