Non-statin option to lower cholesterol

Bempedoic acid, marketed as Nexletol, is a newer medication approved by the FDA to help lower cholesterol levels in patients who have not been successful with other interventions such as lifestyle changes and other cholesterol-lowering medications like statins.

Approved by the FDA in 2020, bempedoic acid works by inhibiting an enzyme in the liver called ATP-citrate lyase, which is involved in the production of cholesterol; any drug in this new category is designated an “ACL inhibitor”. By inhibiting this enzyme needed to synthesize cholesterol, bempedoic acid will lower the levels of LDL (or “bad”) cholesterol in the blood. ACL inhibitors work at an earlier step in the cholesterol production process than HMG-CoA reductase inhibitors (statins).

Of all the markers to describe cardiovascular risk from cholesterol, the MOST important is LDL cholesterol. Why? For every 1 mmol/L, (39 mg/dL) of LDL reduction, the relative risk reduction of cardiovascular events is 22%, AND we see a 10% reduction in mortality!

Bempedoic acid is taken orally once a day and is typically used with other cholesterol-lowering medications. Certain older statins like simvastatin and pravastatin, however, would require a dose adjustment. 

Bempedoic acid has been shown to be effective in reducing LDL cholesterol levels by around 17% when taken with a statin and 28% when taken alone. By comparison, rosuvastatin lowers LDL cholesterol by over 50%. Like statins, bempedoic also reduces the risk of heart attack and is generally well-tolerated.

One potential advantage of bempedoic acid over statins is that it may not have the same risk of muscle-related side effects such as myopathy, which can be a concern with drugs like simvastatin and atorvastatin. Further studies are ongoing to confirm this potential advantage, though the risk of muscle pain is rare even among statin drugs (1-2% of statin users).

Like all medications, bempedoic acid has potential side effects, including elevated uric acid levels and an increased risk of gout. Also, although rare (<1%), bempedoic acid users should report joint swelling or pain, as there are very rare concerns about tendon rupture. As with all treatment choices, it’s important to talk to your doctor or PA about whether bempedoic acid is right for you and to closely monitor for any problems.

One downside of bempedoic acid is cost. While statins are the “King Kong” of cholesterol treatment and only cost less than $10 per month, bempedoic acid will cost $400 per month at full cash price; those with insurance will pay a reduced amount based on the copay and willingness of their plan to share the cost burden.

One combination option to consider is ezetimibe and bempedoic acid, marketed as Nexlizet. Ezetimibe is generic, NOT a statin, and it inhibits the absorption of dietary and biliary cholesterol – decreasing the intestinal absorption by 54%. The combination pill will cost roughly the same as bempedoic acid alone since ezetimibe is an older and cheaper med. While Nexlizet offers an alternative option to statins, even the combination fails to surpass the value of statins in saving lives.

Other non-statin options include fibrates, niacin, fish oil, and cholestyramine. These older options are vastly inferior to statins and surpassed by bempedoic acid and ezetimibe as well. They are rarely recommended now. Bempedoic acid is favored given its proven reduction in major cardiovascular adverse event rates: the hazard ratio is 0.85 compared with placebo.  The older options do not have such evidence of support.

Overall, bempedoic acid represents a promising new non-statin treatment option for patients struggling with high cholesterol levels. It’s always important to work with your healthcare provider to carefully weigh the potential benefits against the risks. At Treasure Valley Family Medicine, we pride ourselves on working closely with our patients to determine the best course of action for everyone.