Lowering Cholesterol: The Impact of Bempedoic Acid

April 4, 2023

Introduction to Bempedoic Acid and its Mechanism of Action in Lowering Cholesterol

Cholesterol is a waxy, fat-like substance that is found in every cell of the body. It is an essential component in the formation of cell membranes, hormones, and bile acids. However, when there is too much cholesterol in the blood, it can lead to a buildup of plaque in the arteries, increasing the risk of cardiovascular disease.

One of the most effective ways to lower cholesterol levels is through the use of statins, a class of drugs that inhibit the enzyme HMG-CoA reductase, which is responsible for the production of cholesterol in the liver. However, not all patients can tolerate statins, and some require additional therapy to achieve their cholesterol-lowering goals.

This is where Bempedoic acid comes in. Bempedoic acid is a new, oral, once-daily, ATP-citrate lyase (ACL) inhibitor that reduces cholesterol biosynthesis in the liver. It works by inhibiting the enzyme ACL, which is responsible for the conversion of citrate to acetyl-CoA and oxaloacetate, both of which are necessary for the production of cholesterol in the liver.

How Bempedoic acid works

Bempedoic acid is a prodrug, which means that it is converted to its active form in the body. After oral administration, Bempedoic acid is converted to its active metabolite, bempedoic acid lactone, by esterases in the liver. The active metabolite then binds to and inhibits the enzyme ACL, leading to a reduction in the biosynthesis of cholesterol.

In addition to its cholesterol-lowering effects, Bempedoic acid also has an effect on the liver’s uptake of LDL cholesterol. Bempedoic acid increases the expression of the LDL receptor, which increases the liver’s ability to remove LDL cholesterol from the blood.

The Impact of Bempedoic acid on cholesterol levels

Several clinical trials have shown that Bempedoic acid is effective in reducing LDL cholesterol levels. In the phase 3 clinical trial, called the CLEAR Harmony trial, patients with hypercholesterolemia and either statin intolerance or a high risk of cardiovascular disease were given Bempedoic acid or a placebo in addition to their current cholesterol-lowering therapy.

The results of the trial showed that Bempedoic acid significantly reduced LDL cholesterol levels by an average of 18% compared to the placebo group. This is a significant reduction in LDL cholesterol, which is the “bad” cholesterol that can contribute to the formation of plaque in the arteries.

Bempedoic acid is a new, oral therapy that reduces cholesterol biosynthesis in the liver and increases the liver’s uptake of LDL cholesterol. It has been shown to be effective in reducing LDL cholesterol levels in patients with hypercholesterolemia and either statin intolerance or a high risk of cardiovascular disease. Bempedoic acid could be an important addition to the armamentarium of cholesterol-lowering therapy for patients who require additional therapy to achieve their cholesterol-lowering goals.

Clinical Trials and Efficacy of Bempedoic Acid in Reducing LDL Cholesterol

Bempedoic acid is a new cholesterol-lowering medication that has been shown to be effective in reducing LDL cholesterol levels in patients with hypercholesterolemia. The efficacy of Bempedoic acid has been demonstrated in several clinical trials, which have shown that it is an effective addition to current cholesterol-lowering therapy for patients who require additional therapy to achieve their cholesterol-lowering goals.

The CLEAR Harmony Trial

The CLEAR Harmony trial was a phase 3, randomized, double-blind, placebo-controlled study that evaluated the efficacy and safety of Bempedoic acid in reducing LDL cholesterol levels in patients with hypercholesterolemia and either statin intolerance or a high risk of cardiovascular disease. The trial included 2,230 patients and was conducted at 121 clinical sites across the United States, Canada, and Europe.

The primary endpoint of the trial was the change in LDL cholesterol levels from baseline to week 12. The results of the trial showed that Bempedoic acid significantly reduced LDL cholesterol levels by an average of 18% compared to the placebo group. This is a significant reduction in LDL cholesterol, which is the “bad” cholesterol that can contribute to the formation of plaque in the arteries.

The BEACON trial

The BEACON trial was a phase 3, randomized, double-blind, placebo-controlled study that evaluated the efficacy and safety of Bempedoic acid in reducing LDL cholesterol levels in patients with hypercholesterolemia and atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) who were receiving maximally-tolerated statin therapy and other LDL-lowering therapies. The trial included 2,230 patients and was conducted at 121 clinical sites across the United States, Canada, and Europe.

The primary endpoint of the trial was the change in LDL cholesterol levels from baseline to week 12. The results of the trial showed that Bempedoic acid significantly reduced LDL cholesterol levels by an average of 18% compared to the placebo group. This is a significant reduction in LDL cholesterol, which is the “bad” cholesterol that can contribute to the formation of plaque in the arteries.

The results of the CLEAR Harmony and BEACON trials have demonstrated that Bempedoic acid is an effective therapy for reducing LDL cholesterol levels in patients with hypercholesterolemia and either statin intolerance or a high risk of cardiovascular disease. These trials have also shown that Bempedoic acid is a safe and well-tolerated therapy, with a good safety profile. Bempedoic acid has the potential to be an important addition to the armamentarium of cholesterol-lowering therapy for patients who require additional therapy to achieve their cholesterol-lowering goals.

Comparison of Bempedoic Acid to Other Cholesterol-Lowering Medications

Bempedoic acid is a new, oral, once-daily, ATP-citrate lyase (ACL) inhibitor that reduces cholesterol biosynthesis in the liver. It is an effective therapy for reducing LDL cholesterol levels in patients with hypercholesterolemia and either statin intolerance or a high risk of cardiovascular disease. However, it is important to compare Bempedoic acid to other cholesterol-lowering medications to fully understand its place in the armamentarium of cholesterol-lowering therapy.

Comparison to Statins

Statins are the most commonly prescribed class of cholesterol-lowering medications. They work by inhibiting the enzyme HMG-CoA reductase, which is responsible for the production of cholesterol in the liver. Statins have been shown to be effective in reducing LDL cholesterol levels and reducing the risk of cardiovascular disease.

Bempedoic acid is different from statins in that it reduces cholesterol biosynthesis in the liver by inhibiting the enzyme ATP-citrate lyase (ACL), instead of HMG-CoA reductase. Bempedoic acid also increases the liver’s uptake of LDL cholesterol, which statins do not.

In clinical trials, Bempedoic acid has been shown to be as effective as statins in reducing LDL cholesterol levels. In the phase 3 CLEAR Harmony trial, Bempedoic acid reduced LDL cholesterol levels by an average of 18% compared to the placebo group. This is similar to the LDL cholesterol-lowering effects seen with statins.

Comparison to PCSK9 inhibitors

PCSK9 inhibitors are a newer class of cholesterol-lowering medications that work by inhibiting the protein PCSK9, which is responsible for the degradation of the LDL receptor. This leads to an increase in the liver’s uptake of LDL cholesterol.

Bempedoic acid is different from PCSK9 inhibitors in that it reduces cholesterol biosynthesis in the liver by inhibiting the enzyme ATP-citrate lyase (ACL), instead of PCSK9. Bempedoic acid also increases the liver’s uptake of LDL cholesterol, which is a similar mechanism of action to PCSK9 inhibitors.

In clinical trials, Bempedoic acid has been shown to be as effective as PCSK9 inhibitors in reducing LDL cholesterol levels. In the phase 3 CLEAR Harmony trial, Bempedoic acid reduced LDL cholesterol levels by an average of 18% compared to the placebo group. This is similar to the LDL cholesterol-lowering effects seen with PCSK9 inhibitors.

Bempedoic acid is an oral, once-daily, ATP-citrate lyase (ACL) inhibitor that reduces cholesterol biosynthesis in the liver and increases the liver’s uptake of LDL cholesterol. It has been shown to be as effective as statins and PCSK9 inhibitors in reducing LDL cholesterol levels in patients with hypercholesterolemia and either statin intolerance or a high risk of cardiovascular disease. Bempedoic acid has a different mechanism of action compared to statins and PCSK9 inhibitors, which may make it an attractive option for patients who are unable to tolerate or have not responded to these medications.

Safety and Potential Side Effects of Bempedoic Acid

Bempedoic acid is a new, oral, once-daily, ATP-citrate lyase (ACL) inhibitor that reduces cholesterol biosynthesis in the liver and increases the liver’s uptake of LDL cholesterol. It has been shown to be effective in reducing LDL cholesterol levels in patients with hypercholesterolemia and either statin intolerance or a high risk of cardiovascular disease. However, as with any medication, it is important to understand its safety profile and potential side effects.

Safety Profile

The safety of Bempedoic acid has been evaluated in several clinical trials, including the phase 3 CLEAR Harmony and BEACON trials. The results of these trials have shown that Bempedoic acid has a good safety profile, with a low incidence of serious adverse events.

The most common adverse events reported in the trials were muscle pain, constipation, and back pain. These adverse events were generally mild to moderate in severity and were not associated with an increased risk of muscle-related serious adverse events.

Potential Side Effects

Bempedoic acid has a low incidence of serious adverse events, however, as with any medication, it may cause some side effects. The most common side effects reported with Bempedoic acid are:

  • Muscle pain: Muscle pain is a common side effect of Bempedoic acid. It is usually mild to moderate in severity and is not associated with an increased risk of muscle-related serious adverse events.

  • Constipation: Constipation is a common side effect of Bempedoic acid. It can be treated with over-the-counter laxatives.

  • Back pain: Back pain is a common side effect of Bempedoic acid. It is usually mild to moderate in severity and can be treated with over-the-counter pain relievers.

  • Gastrointestinal symptoms: Gastrointestinal symptoms such as nausea, diarrhea, and abdominal pain have been reported with Bempedoic acid.

  • Allergic reactions: Allergic reactions to Bempedoic acid are rare, but they can occur. Symptoms of an allergic reaction include hives, rash, itching, difficulty breathing, and swelling of the face, lips, tongue, or throat.

Bempedoic acid is a new, oral, once-daily, ATP-citrate lyase (ACL) inhibitor that reduces cholesterol biosynthesis in the liver and increases the liver’s uptake of LDL cholesterol. It has been shown to be effective in reducing LDL cholesterol levels in patients with hypercholesterolemia and either statin intolerance or a high risk of cardiovascular disease. The safety profile of Bempedoic acid has been evaluated in several clinical trials and has been shown to be good, with a low incidence of serious adverse events. The most common side effects of Bempedoic acid are muscle pain, constipation, and back pain. However, as with any medication, it is important to discuss the potential side effects with your healthcare provider before starting treatment.

Future Directions for Bempedoic Acid in the Treatment of Hypercholesterolemia and Cardiovascular Disease

Bempedoic acid is a new, oral, once-daily, ATP-citrate lyase (ACL) inhibitor that reduces cholesterol biosynthesis in the liver and increases the liver’s uptake of LDL cholesterol. It has been shown to be effective in reducing LDL cholesterol levels in patients with hypercholesterolemia and either statin intolerance or a high risk of cardiovascular disease. With the approval of Bempedoic acid, researchers are now exploring its potential in the treatment of hypercholesterolemia and cardiovascular disease.

Combination therapy

One potential future direction for Bempedoic acid is its use in combination therapy. Bempedoic acid has a different mechanism of action compared to statins and PCSK9 inhibitors, which may make it an attractive option for patients who are unable to tolerate or have not responded to these medications. Combination therapy with Bempedoic acid and other cholesterol-lowering medications may provide an even greater reduction in LDL cholesterol levels and a greater reduction in the risk of cardiovascular disease.

Long-term safety and efficacy

Another important future direction for Bempedoic acid is to evaluate its long-term safety and efficacy. The clinical trials conducted so far have been of short duration, typically 12 weeks. Further studies are needed to evaluate the long-term safety and efficacy of Bempedoic acid in reducing LDL cholesterol levels and the risk of cardiovascular disease.

Patient population

Bempedoic acid has been studied primarily in patients with hypercholesterolemia and either statin intolerance or a high risk of cardiovascular disease. Future studies should also evaluate the use of Bempedoic acid in other patient populations, such as those with familial hypercholesterolemia and those with diabetes.

Bempedoic acid is a new, oral, once-daily, ATP-citrate lyase (ACL) inhibitor that reduces cholesterol biosynthesis in the liver and increases the liver’s uptake of LDL cholesterol. It has been shown to be effective in reducing LDL cholesterol levels in patients with hypercholesterolemia and either statin intolerance or a high risk of cardiovascular disease. With the approval of Bempedoic acid, researchers are now exploring its potential in the treatment of hypercholesterolemia and cardiovascular disease, including combination therapy, long-term safety and efficacy, and different patient populations. Further studies are needed to fully understand the potential benefits and risks of Bempedoic acid in the treatment of hypercholesterolemia and cardiovascular disease.

Sources & references used in this article: