1216-Feature-Top Ten_Blog

Editor’s note: This is one in a 10-part series of the top medical research advances in 2015 as determined by American Heart Association volunteer and staff leaders.

The blockbuster drugs known as statins are teaming with a new medication to lower the level of bad LDL cholesterol by an additional 60 percent, signaling what researchers are calling the arrival of the first highly effective cholesterol-lowering drugs in a generation.

The new drugs, called Praluent (alirocumab) and Repatha (evolocumab), are a new class of cholesterol-lowering medicines called PCSK9 inhibitors. The findings, published in two studies this spring in the New England Journal of Medicine, were selected as a top 10 research advance in 2015.

“High-intensity statins reduce LDL up to 50 percent, but if you add a PCSK9 inhibitor to that, you reduce LDL another 50 to 70 percent on top of statins. It’s remarkable,” said University of Iowa epidemiologist Jennifer Robinson, M.D., who led the Praluent study and was an investigator on the Repatha trial.

High cholesterol is a strong risk factor for heart disease and stroke, the nation’s No. 1 and No. 5 killers. Current guidelines recommend doctors consider statin treatment for adults at high risk of heart attacks and strokes.

The new drugs target PCSK9, a protein that destroys LDL receptors – little keyholes that sit on the surface of liver cells and remove LDL cholesterol from the blood. By blocking PCSK9 from doing its job, those receptors blanket liver cells and keep clearing LDL over and over again.

“The LDL receptor can be recycled 100 times,” said Marc Sabatine, M.D., a cardiologist at Brigham and Women’s Hospital and a professor at Harvard Medical School in Boston.

Statins work differently by preventing the formation of cholesterol.

Nearly half of the 78 million U.S. adults who should be taking cholesterol-lowering drugs are not, according to a recent report from the Centers for Disease Control and Prevention. Statins have been the mainstay treatment for lowering bad cholesterol since the late 1980s.

But for some high-risk patients, statins aren’t enough.

“For individuals with a genetic predisposition to high LDL, their risk of cardiovascular events is quite high,” said Sabatine, who led the Repatha study. “Their LDL can be at 200 or higher, so even if you cut that in half with statins, that’s not good enough.”

Familial hypercholesterolemia, or FH, is a genetic condition that affects as many as one in 200 people and causes up to three times the normal level of LDL. The Food and Drug Administration this summer approved Praluent and Repatha for adults with FH and others at increased risk for heart attacks and strokes who require additional lowering of LDL.

Despite the cholesterol-plunging data, definitive proof is still to come about the drugs’ ability to prevent heart attacks, strokes and deaths – and to do it safely. Large clinical trials are under way, with results expected starting in late 2016.

“Right now, as we await the formal outcome studies to determine both efficacy and safety, we reserve these drugs for people with the very highest levels of LDL that essentially have FH for whom statin therapy has been wholly inadequate,” said cardiologist Neil Stone, M.D., who runs the lipid clinic at Northwestern Memorial Hospital in Chicago.

For the average person who needs to lower their risk of heart attack and stroke, statins are still the drug of choice, said Stone, who chaired the committee that wrote the American Heart Association’s cholesterol guidelines.

Robinson was also part of the committee and said the guidelines likely won’t change until the outcomes data are in for the costly drugs.

Praluent and Repatha, both given as injections, have a list price of more than $14,000 a year. Most statins, on the other hand, are available as low-cost generics.

Also selected as a top 10 research advance in 2015 is a study that looked at the other type of cholesterol – HDL, the so-called good cholesterol that removes fat from the walls of blood vessels.

Doctors have long thought that pushing HDL levels higher could help reduce the risk of heart disease. But researchers reported in The Lancet Diabetes and Endocrinology in May that what matters more than HDL quantity is HDL quality.

Using blood samples from a large, long-running British study, researchers found that the better HDL works, the lower the risk of heart disease later in life.

The study implies that therapies to boost HDL function rather than HDL amounts may better protect against heart disease, researchers said.