There are powerful cholesterol-lowering medicines making waves. Many health professionals are convinced that there is no such thing as too low a golf score or a cholesterol level. They are right about golf, but we’re not so sure about cholesterol. The FDA approved Repatha to lower LDL cholesterol on August 27, 2015. It followed the approval of a somewhat similar drug, Praluent, on July 24, 2015. These PCSK9 inhibitors have been catching on with doctors and patients. How good is the evidence Repatha and Praluent will save lives and what are the potential complications?
What are PCSK9 Inhibitors?
This is complicated, but I will do my best to simplify and keep it short. PCSK9 is a mouthful and stands for proprotein convertase subtilisin/kexin type 9. Drug companies discovered a way to inhibit this enzyme on chromosome 1. You might think they would have come up with a simplified description other than PCSK9 inhibitor, but that is what we ended up with.
The bottom line is that these drugs are monoclonal antibodies or “MABS,” “mAbs” or “mabs.” PCSK9 inhibitors latch on to receptors and lower LDL cholesterol by 50 to 60% (StatPearls, May 13, 2022). Because most cardiologists believe that LDL-C (low-density lipoprotein cholesterol) is the # 1 bad actor in heart disease, lowering this risk factor is the most important thing they can do to reduce the risk for clogged coronary arteries and heart attacks.
The FDA Guidelines for Repatha to Lower LDL Cholesterol:
Gird your loins! We are about to pass through the looking glass of FDAspeak. We usually do not like to quote the technical language the FDA requires on drug labels. That’s because it can be hard to understand. This is a bit more dense than usual, but please hang in there with us.
“INDICATIONS and USAGE:
REPATHA is indicated:
- “In adults with established cardiovascular disease to reduce the risk of myocardial infarction, stroke, and coronary revascularization
- “As an adjunct to diet, alone or in combination with other low-density lipoprotein cholesterol (LDL-C)-lowering therapies, in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH), to reduce LDL-C
- “As an adjunct to diet and other LDL-C-lowering therapies in pediatric patients aged 10 years and older with HeFH, to reduce LDL-C
- “As an adjunct to other LDL-C-lowering therapies in adults and pediatric patients aged 10 years and older with homozygous familial hypercholesterolemia (HoFH) to reduce LDL-C
What the FDAspeak Means:
We interpret the official “indications” for evolocumab above to mean that when diet and other cholesterol-lowering treatments (like high-dose statin therapy) don’t achieve the desired results, then Repatha to lower LDL cholesterol might be added to the mix. This would be for people diagnosed with familial hypercholesterolemia or atherosclerotic cardiovascular disease. Your average Joe with elevated LDL cholesterol would not be included in these official indications, unless he has “established” cardiovascular disease.
Please note that the FDA used to require the company to state that the ability of the drug to prolong life “has not been determined.” That was dropped when the labeling was changed in December, 2017.
TV Commercial for Repatha to Lower LDL Cholesterol:
Have you seen the television commercial for Repatha to lower LDL cholesterol?
An announcer asks:
“Working hard to lower your LDL bad cholesterol? Not making enough progress? You eat well. Take the highest dose statin you can, but still aren’t getting where you need to be. Now there’s Repatha, a different way to reduce LDL and get on the path to dramatically lower numbers.”
The video shows a man pedaling a bicycle downhill as fast as he can but making very little progress. Other people go zipping by at normal speed. One guy looks disdainfully at our frustrated bike rider as he passes by. Another fellow is shown trying to slowly walk down the up escalator. People go past him fast on the down escalator.
Later we see our bike rider going down hill at a normal clip and our escalator walker moving fast on the down escalator. Presumably, they are modeling downward progress thanks to Repatha to lower LDL cholesterol. See the commercial yourself at this link.
We may have missed it, but nowhere in the commercial did we see or hear reference to the FDA approved indications. In other words, neither familial hypercholesterolemia nor clinical atherosclerotic cardiovascular disease were mentioned. Our average Joe might assume that Repatha to lower LDL cholesterol could be just the ticket. Perhaps he’d follow the announcer’s suggestion to “ask if Repatha can you get on the path to way lower LDL.”
Commercials Work:
Drug companies would not spend big bucks making television commercials and buying air time if they didn’t work.
Here is a question we received from a reader who wants to know about Repatha to lower LDL cholesterol:
Q. After years of taking statins and suffering many horrible side effects such as muscle pain, a rise in blood sugar and mental fog, I’ve finally gotten my doctor to agree I should stop taking a statin. Now he wants me to take Repatha. What are the side effects of that drug? Am I jumping from the frying pan into the fire?
A. Repatha (evolocumab) and a similar drug Praluent (alirocumab) are referred to as PCSK9 inhibitors. These injectable medications are very effective for lowering LDL cholesterol. Unlike statins, they don’t usually cause muscle pain, changes in blood sugar or brain fog.
The most common symptoms of these drugs include injection site reactions, cold-like symptoms and urinary tract infections.
Although there is no mention in the prescribing information about psychological side effects, some patients experience them (British Journal of Clinical Pharmacology, Dec. 2022; CNS Neuroscience & Therapeutics, Nov. 10, 2023).
One reader shared this experience:
“I developed severe depression while taking Repatha. It took me a horrible nine months to realize the drug was making me suicidal. If I wasn’t sleeping, I was crying. I couldn’t think straight anymore.
“My adult daughter helped me realize Repatha was causing the depression. I slowly started feeling better after stopping the injections.
“Of course, my doctor said it couldn’t have been the drug because depression wasn’t listed as a side effect.”
For more in-depth information about these medications and other ways to lower blood lipids, you may wish to read our eGuide to Cholesterol Control and Heart Health. This online resource can be found under the Health eGuides tab.
Repatha (Evolocumab) Side Effects:
Side effects may include infections of the respiratory system or urinary tract. Some people also experience headache, dizziness, cough, back pain, muscle pain or reactions at the injection site. Life-threatening allergic reactions are the most serious complication.
The Repatha website lists this Important Safety Information:
“What are the possible side effects of Repatha®?
“Repatha® can cause serious side effects including: Repatha® may cause allergic reactions that can be serious. Call your healthcare provider or go to the nearest hospital emergency room right away if you have any symptoms of an allergic reaction including a severe rash, redness, severe itching, a swollen face, or trouble breathing.
“The most common side effects of Repatha® include: runny nose, sore throat, symptoms of the common cold, flu or flu-like symptoms, back pain, high blood sugar levels (diabetes), and redness, pain, or bruising at the injection site.
“Tell your healthcare provider if you have any side effect that bothers you or that does not go away.
“These are not all the possible side effects of Repatha®. Ask your healthcare provider or pharmacist for more information. Call your healthcare provider for medical advice about side effects.”
“You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.
The High Cost of Repatha:
If your insurance company won’t cover Repatha, you may end up spending at least $600 a month.
Here is what some readers have to say:
JuneBug 14 offered this perspective:
“I looked up Repatha and the mortality rate is the same as NOT taking it. Insurance won’t pay for it, and why would I put my family through that expense?”
Steven in Georgia is caught in a bind:
“I have tried many statin-type cholesterol-lowering drugs through my doctor to no avail. Every one of them gave me severe muscle pain. Repatha became available and I got on the trials of that. This drug knocked my numbers down from my 290-300 to barely 100 or so. But after months of trying, my doctor could not get my insurance company to approve it.
“He sent me to a cardiologist to see if he could get my insurance company to approve it. The cardiologist started me on Praluent, a somewhat similar drug. I tried it a couple of times and it just made me feel different. That’s about the best description I can give on that. Then my muscles started hurting again…Needless to say, I stopped using it. Now I am on the road to a natural fix for my cholesterol.”
A Message from Danish Physician, Uffe Ravnskov:
A renowned cholesterol skeptic and author of The Cholesterol Myths, Uffe Ravnskov, MD, PhD, wrote this on our website on April 18, 2017:
“The Repatha trial was originally planned to go on for 4 years, but as the number of heart events was significantly lower in the treatment group already after 26 months, the authors decided to stop the trial.
“But the number of deaths, both from heart disease and from other causes, had increased! Not with statistical significance, but it might have become significant if the trial had continued. A relevant question is therefore: Did they stop the trial because the total number of events had become significantly lower in the treatment group, or because the number of deaths was increasing?
“How do they explain that 444 died in the treatment group, but only 426 among the untreated? I mean, if ‘bad’ high LDL-cholesterol was the cause of atherosclerosis and heart disease, then we should expect that a 59% lowering of this ‘poisonous’ molecule should lower mortality, not increase it.
“The reason is of course that a high level of LDL-cholesterol is not poisonous; it is beneficial, as we have documented in a review of 19 studies including more than 68,000 people above the age of 60 published in BMJ Open. Almost all studies found that elderly people with the highest levels of the ‘bad’ LDL-cholesterol live the longest; even longer than those on statin treatment; no study found the opposite. A reasonable question is therefore: Why should we lower the bad cholesterol if those with the highest values live the longest?”
Does Repatha Help People Live Longer?
The question that Dr. Ravnskov asks above is highly relevant. How many lives are saved when people take a PCSK9 inhibitor like evolocumab? The largest trial to date is the FOURIER trial he describes above. There were 13,784 people who received Repatha in that study. Another 13,780 received placebo. At the end of the trial 251 people had died as a result of “cardiovascular mortality” while taking Repatha. 240 died due to cardiovascular mortality in the placebo group. That is hardly a great outcome.
A study published in PLos One, Dec. 6, 2023 reviewed several different clinical trials of PCSK9 inhibitors, including Repatha. The FOURIER trial was included in that analysis. We are not statisticians or number crunchers. We would be the first to admit that we are swimming upstream when it comes to calculating things like absolute risk reduction and number needed to treat (NNT).
According to our analysis, 1.28% of volunteers taking Repatha died from cardiovascular causes in these trials. At the same time, 1.38% of those on placebo died from cardiovascular causes. That gives us an absolute risk reduction of 0.1% and a number needed to treat of 1000. In other words, a thousand people would have had to take evolocumab to prevent one death from heart attack, stroke or other cardiovascular causes.
Weighing the Decision to Take Repatha:
We leave it to you and your physician to determine the benefits and risks of PCSK9 inhibitors in your situation. During such discussions, it is always helpful to have a prescriber provide actual numbers. Here are some questions to ask:
- Doctor, how many people have to take this medicine for one person to avoid a bad outcome such as a heart attack, stroke, or premature death? That is the NNT (number needed to treat). If more than 50 or 60 have to take a medicine for 1 person to avoid a problem, it is not a very impressive result.
- Doctor, what is the absolute risk reduction for the outcome I am trying to avoid? Drug companies love to promote the relative risk reduction rather than the absolute risk reduction. Our favorite example is an old Lipitor advertisement. The company bragged that atorvastatin lowered the risk of heart attacks by 36% after 5 years. But the company admitted “That means in a large clinical study, 3 percent of patients taking a sugar pill or placebo had a heart attack compared to 2 percent of patients taking Lipitor.” That is the absolute risk reduction. 1% does not seem nearly as impressive as 36%, does it?
- Doctor, what is the likelihood I will experience a side effect with this medicine? Please provide the numbers from the clinical trials. Are there any symptoms that are so serious I should report them to you immediately?
What’s Your Experience with Repatha to Lower LDL Cholesterol?
We would love to know more about how people are faring with Repatha or Praluent. Share your story below in the comment section. You can learn more about these and other cholesterol lowering drugs in our eGuide to Cholesterol Control & Heart Health. This online resource can be found under the Health eGuides tab. It also discusses non-drug approaches to heart health.
