Bempedoic Acid: An Option for Those With True Statin Intolerance?

The skeptical cardiologist has updated his post from 2017 entitled “Are you on the fence about statin drugs?”. You’ll be happy to hear that Geo, the subject of that post, is doing well on the therapeutic pathway he selected.

I sent this out as a Substack email which you can access here. There are comments from readers and responses from me at the Substack link which you may find of interest.

One reader described his inability to tolerate atorvastatin and simvastatin. On both he had significant myalgias. I responded thusly:

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 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.

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 was 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 increase rate of gall stones, 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