Diabetes Forecast

PCSK9 Drugs Lower "Bad" Cholesterol

By Allison Tsai , ,

Not all cholesterol is created equal. While it’s true that a certain type—LDL—can harm your health, HDL is actually beneficial. It helps clear cholesterol from your arteries and protects you from having a heart attack or stroke. Problems occur when someone has high levels of LDL—cholesterol builds up in the arteries, which increases the risk for heart attack, stroke, and peripheral artery disease—or low levels of HDL, because cholesterol isn’t cleared from the arteries as efficiently.

For most people with diabetes, statins (a group of cholesterol-lowering drugs) are enough to keep the LDL in check. In fact, the American Diabetes Association recommends that all people with diabetes over age 40 who don’t have heart disease go on statin therapy.

But for certain individuals, statins, along with other cholesterol-lowering medications, aren’t enough. That’s why scientists have developed a new class of injectable LDL-lowering drugs, called PCSK9 inhibitors. In clinical trials, they’ve reduced LDL cholesterol by up to 60 percent, says Robert Eckel, MD, professor of medicine in the Division of Endocrinology, Metabolism, and Diabetes and the Division of Cardiology at the University of Colorado Anschutz Medical Campus in Denver. The two PCSK9 drugs currently on the market are alirocumab (Praluent), manufactured by Sanofi and Regeneron, and evolocumab (Repatha), manufactured by Amgen.

Top Candidates

PCSK9 inhibitors aren’t for everybody, says Rachel Rocha, PharmD, CDE, BC-ADM, a clinical pharmacist with ProMedica Toledo Hospital in Ohio. According to the Food and Drug Administration (FDA), people with or without diabetes have to fit into one of these three categories to be a candidate for PCSK9 inhibitors:

  • Familial Hypercholesterolemia. This genetic disorder blocks the liver from removing LDL from the body, which results in very high LDL levels and a high risk for cardiovascular disease. PCSK9 inhibitors unlock the liver’s ability to process LDL despite the genetic mutation, says Eckel, who has served as an expert witness for Sanofi/Regeneron. (See “Get to Know PCSK9 Inhibitors,” below.)

  • Prior Heart Attack or Stroke. People who have already had a cardiovascular event, take statins, and still have LDL levels above their target range can benefit from PCSK9 inhibitors, says Rocha.

  • Statin Intolerance. If your LDL levels are high and you’ve had a heart attack or stroke but can’t tolerate the recommended statin dose, you may be considered for PCSK9 inhibitors, Rocha says. That said, you may have a harder time getting insurance coverage for this indication.

The Good

Many of the PCSK9 inhibitor clinical trials included people with diabetes, says Holly Gurgle, PharmD, BCACP, CDE, an assistant professor at the University of Utah College of Pharmacy and practitioner at the ARUP Family Health Clinic in Salt Lake City. The medications show the same results in people with and without diabetes. “In most studies, we’re seeing 60 percent reductions in LDL, and that’s on top of reductions for people who are already treated with statins,” says Gurgle. “Statins can reduce LDL up to 50 percent, so very, very low levels of LDL are being achieved with these medications.”

Perhaps more important is the theory that these low LDL levels may decrease the risk of certain heart problems. In a 2017 study published in the New England Journal of Medicine, people with a history of heart disease who took the PCSK9 inhibitor Repatha along with a statin for two years had a 15 percent lower risk for cardiovascular events, such as heart attack and stroke. That’s encouraging, but there are still a lot of unanswered questions, such as whether PCSK9 inhibitors are beneficial and cost-effective for lower-risk people, including those who have never had a heart attack or stroke.

In addition, side effects are minimal, says Rocha, and the drugs don’t interact with any other diabetes medications. The biggest complaint is injection site reactions, such as redness, swelling, and pain. But because PCSK9 inhibitors are injected under the skin just once or twice a month, such reactions typically don’t stop people from using the drugs.

The Cost

While PCSK9 inhibitors work quite well, the expense is a major downside, says Eckel. Without insurance, the medication costs about $14,500 a year. And even with insurance, cost is a concern. Because they’re considered specialty drugs, it can be difficult to get insurance approval. “You really have to follow the [FDA] indications stringently to get these drugs approved by the third-party payer,” Eckel says.

Even then, it can be a challenge. Sometimes insurers will ask that you try another medication first, approving your PCSK9 inhibitor prescription only if your LDL remains elevated. Once you have a prescription, there are manufacturer programs that can help bring down the cost, says Gurgle.

The Alternatives

Cholesterol medication isn’t the only tool in the toolbox when it comes to preventing heart disease. Blood pressure medication, anti-platelet drugs (such as aspirin), and diet and exercise also play an important role. “[PCSK9 inhibitors] are just one piece of the puzzle,” Gurgle says.

Get to Know PCSK9 Inhibitors

Understanding how a drug works in the body can be complex, and sometimes scientists aren’t even sure why a drug is effective. Here’s what we know about PCSK9 inhibitors:

How do PCSK9 inhibitors work?

LDL receptors remove LDL cholesterol from the bloodstream, shuttling it into the cells to either process or expel. PCSK9 is a liver protein that binds to LDL cholesterol receptors in the liver and breaks them down, preventing the liver from processing the LDL cholesterol and expelling it from the body, says Holly Gurgle, PharmD, BCACP, CDE, an assistant professor at the University of Utah College of Pharmacy and a practitioner at the ARUP Family Health Clinic in Salt Lake City. PCSK9 inhibitors block the breakdown of those receptors, which allows the receptors to better clear LDL from the blood. This can lead to lower LDL levels.

What about side effects?

The targeted nature of PCSK9 inhibitors, which block a specific protein, usually equates to few side effects, says Rachel Rocha, PharmD, CDE, BC-ADM, a clinical pharmacist with ProMedica Toledo Hospital in Ohio. While injection site irritation can occur, PCSK9 inhibitors generally lead to fewer side effects than statins.



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