Bempedoic Acid
Another effective option for lipid-lowering in those who are intolerant of statins
Several readers of my last newsletter made comments about side effects they had experienced on statin drugs.
One reader described his inability to tolerate atorvastatin and simvastatin. On both, he had significant myalgias. My response included comments about two good options we have for those unable to tolerate statins:
Fortunately, we have some great options for patients like you who are at high ASCVD risk but have significant intolerance to statins. Ezetimibe has an excellent side effect profile and has shown improved outcomes. The PCSK9 inhibitors are very effective with good outcome data and minimal side effects.
Yesterday, we heard at the ACC that bempedoic acid lowers major adverse cardiac events (MACE) in statin-intolerant high risk patients. All of these drugs, by the way, work by one method or another to lower apo B and LDL levels.
That same day, the CLEAR Outcomes trial was published which proved the safety and effectiveness of a new medication for the statin intolerant.
Bempedoic Acid
The newcomer in medical options for those intolerant to statins, bempedoic acid, targets cholesterol synthesis in the liver by inhibiting ATP-citrate lyase (ACL), two steps upstream of HMG CoA reductase, the statin target. Because it is administered as a prodrug and is converted to active coenzyme A form by enzymes found only in the liver and not in muscles it is a promising alternative for patients like my reader (and several of my patients) who have well-characterized statin-associated muscle symptoms (SAMS).
I used the phrase well-characterized SAMS because through a process of withdrawal and re-challenge we discover in many patients that the aches or pains in joints or muscles they had experienced on a statin were not due to the statin but other factors.
The true SAMS population is small and real but very vocal. It is likely now that bempedoic acid has approval, marketing from the maker will focus on direct-to-consumer advertising, emphasizing the syndrome of SAMS.
In my clinic, we have been able to achieve target apo B levels in those with SAMS or other reasons for statin intolerance utilizing combinations of ezetimibe and PCSK9 inhibitor drugs. There are a few patients who don't seem to tolerate any of these 3 agents although they work in entirely different ways. They tend to have very idiosyncratic side effects (like lower back pain or diarrhea) and also have side effects from multiple other medications.
I suspect that the patient intolerant of the 3 existing medications will experience the same side effects on bempedoic acid but I will offer it to them. I'll be sure to mention the increased rate of gallstones, gout, and renal impairment in the bempedoic acid group. And the high price.
John Mandrola has written his analysis of the trial for Medscape
To me, when prevention of future cardiac events is an important goal for a patient, statins should be strongly favored. When the issue of statin adverse effects comes up, we should be facile in the discussion of the lack of evidence for placebo-resistant adverse effects from statins.So, the higher cost of bempedoic acid over atorvastatin is a positive because it will incentivize us to use statins, the drugs with the much stronger evidence base.
As usual (except when it comes to coronary artery calcium scans), Mandrola has performed a wise, conservative analysis and an approach I can endorse.
Skeptotolerantly Yours,
-ACP
Like I said, we have cheaper and more effective alternatives. Likely a small niche.
Drug companies are going to keep making lots of money until the US can figure out a way to get drug prices under control.
As to doctors, the principal investigators on these types of studies don't receive any direct renumeration. And my sense most of them are dedicated to patient care and finding better treatments. But often there are paid talks, enhanced prestige, and other benefits for the thought and study leaders in these areas.
After years of well-meaning docs attempting to "re-challenge" me with various statins (never ending well), finally one thought to prescribe ezetimibe (as a mono therapy). It actually has made a significant improvement in my lipids without the physical side effects and brain fog I experience on statins. Sounds like bempedoic acid might be something else to try. I'm also "sub-clinical hypothyroid" taking 50 mcg of levothyroxine daily and have borderline kidney disease (eGFR of 60) but (maybe) oddly improvements to to my lipid labs seem to correlate with an undesirable increase in TSH and a lowered eGFR. Go figure. I'm almost 70, and a recent PET stress test shows normal results with no apparent blockages, etc. It's almost as though my body is saying "I need my lipids, leave me alone!"