What is Bempedoic Acid?

Bempedoic acid is a novel cholesterol-lowering drug specifically designed to reduce LDL cholesterol in the blood. Unlike statins, which have been the standard treatment for decades, bempedoic acid works through a different mechanism, making it a promising option for people who cannot tolerate statins. Classified as an ATP-citrate lyase inhibitor, bempedoic acid blocks a key enzyme early in the cholesterol synthesis pathway, which leads to a reduction in the liver's production of cholesterol.

One of the unique features of bempedoic acid is that it is a prodrug, meaning it is inactive when first ingested and only becomes active when it is metabolized in the liver. This localized activation minimizes the potential for muscle-related side effects, a common issue with statins. Because of this, bempedoic acid is especially beneficial for patients who experience statin intolerance. In addition, it has shown efficacy in patients with familial hypercholesterolemia and those who need additional cholesterol-lowering support beyond what can be achieved with statins or other medications alone.

How Does Bempedoic Acid Lower LDL Cholesterol?

Bempedoic acid lowers LDL cholesterol by targeting a critical step in the cholesterol production pathway, different from the mechanisms used by statins. It works by inhibiting ATP-citrate lyase, an enzyme involved in the early stages of cholesterol synthesis in the liver. By blocking this enzyme, bempedoic acid reduces the liver’s ability to produce cholesterol, particularly the low-density lipoprotein (LDL) form that is most closely associated with cardiovascular disease.

This reduction in cholesterol synthesis triggers a compensatory mechanism within the liver: the upregulation of LDL receptors. These receptors are responsible for removing LDL cholesterol from the bloodstream, and when their activity increases, more LDL cholesterol is cleared from circulation. The result is a significant reduction in overall LDL levels, which lowers the risk of plaque buildup in the arteries, a key factor in the development of heart disease.

What sets bempedoic acid apart from other cholesterol-lowering treatments is its liver-specific action. Unlike statins, which affect cholesterol synthesis throughout the body, bempedoic acid is activated only in the liver. This localized effect helps minimize the muscle-related side effects often associated with statins, such as myopathy and muscle pain. For this reason, bempedoic acid has emerged as an attractive option for patients who cannot tolerate statins or for those who need additional help lowering their LDL levels beyond what other therapies can achieve.

Bempedoic Acid vs. Other Cholesterol-Lowering Medications

Bempedoic acid offers a unique option in the landscape of cholesterol-lowering medications, standing out from more well-known treatments like statins and PCSK9 inhibitors. While each of these therapies effectively reduces LDL cholesterol, they differ in their mechanisms of action, side effect profiles, and patient suitability.

Bempedoic Acid vs. Statins
Statins work by inhibiting HMG-CoA reductase, another enzyme involved in cholesterol synthesis. This reduces cholesterol production throughout the body, which can lead to a reduction in LDL levels but is also associated with widespread side effects, particularly muscle pain and weakness. Bempedoic acid, on the other hand, targets ATP-citrate lyase, an enzyme that operates earlier in the cholesterol production process and is activated primarily in the liver. Because bempedoic acid does not become active in muscle tissue, patients who experience muscle-related side effects from statins often find relief when switching to or adding bempedoic acid. However, statins tend to offer a higher reduction in LDL cholesterol overall, so for some patients, bempedoic acid may be used in combination with low-dose statins to balance efficacy and tolerability.

Bempedoic Acid vs. PCSK9 Inhibitors
PCSK9 inhibitors, such as evolocumab (Repatha) and alirocumab (Praluent), work by blocking a protein that degrades LDL receptors on liver cells. With more LDL receptors available, the liver can clear more LDL cholesterol from the bloodstream. PCSK9 inhibitors are typically administered via injection and are highly effective at lowering LDL cholesterol, sometimes achieving reductions of up to 60%. While these drugs are powerful, their high cost and the need for injections make them less convenient than oral medications like bempedoic acid. For patients who require significant LDL reduction but are looking for an oral alternative, bempedoic acid can serve as a more accessible option, especially when used alongside other oral medications such as statins or ezetimibe.

Combination Therapy
One of the most promising aspects of bempedoic acid is its potential when used in combination with other cholesterol-lowering drugs. For instance, pairing bempedoic acid with ezetimibe, which blocks cholesterol absorption in the intestine, can produce an additive effect, leading to greater reductions in LDL cholesterol. Similarly, using bempedoic acid alongside low-dose statins can help patients who cannot tolerate high-dose statins but still need substantial LDL reduction.

In summary, bempedoic acid fills an important niche in cholesterol management, particularly for patients who are statin-intolerant or seeking alternatives to injectable therapies. While it may not be as potent as some other treatments, its oral administration, unique mechanism, and favorable side effect profile make it a valuable option in the broader toolkit for managing LDL cholesterol.

Clinical Evidence Supporting Bempedoic Acid

Bempedoic acid's efficacy and safety have been supported by a number of clinical trials, which highlight its ability to lower LDL cholesterol and offer a suitable alternative for certain patient populations. These studies have provided insights into the drug’s performance, including its effectiveness in statin-intolerant patients and its overall cardiovascular benefits.

Key Clinical Trials One of the most notable studies evaluating bempedoic acid is the CLEAR Harmony trial. This large-scale, phase 3 clinical trial involved over 2,200 patients with elevated LDL cholesterol levels who were either statin-intolerant or could not achieve sufficient LDL reduction with statins alone. Over 12 weeks, bempedoic acid showed an average LDL reduction of approximately 18% compared to placebo. This might seem modest compared to statins or PCSK9 inhibitors, but for patients who cannot tolerate those therapies, it represents a significant step forward in cholesterol management.

Combination Therapy Insights Additional studies have demonstrated the benefits of using bempedoic acid alongside other cholesterol-lowering medications. The CLEAR Wisdom trial evaluated bempedoic acid in combination with statins or ezetimibe and found that when added to a statin, bempedoic acid resulted in an additional 17% LDL reduction. This evidence highlights its value as an adjunct therapy for patients who need to further lower their cholesterol but cannot increase their statin dose due to side effects.

Safety and Side Effects Bempedoic acid’s safety profile is one of its strongest selling points, particularly for patients who experience muscle-related side effects from statins. Across multiple trials, bempedoic acid has been associated with a lower incidence of muscle pain and weakness, making it an attractive alternative. However, it does carry some risks of other side effects, such as elevated uric acid levels, which can potentially lead to gout in susceptible individuals. Despite these concerns, the overall safety data are encouraging, and the drug has been well tolerated by most patients.

Canadian-Specific Data Though the global trials are widely referenced, Canadian-specific data also support the use of bempedoic acid. Health Canada has approved the medication based on robust evidence from these international studies, and ongoing monitoring in the Canadian population is helping to further refine its role in local healthcare practices. As its use continues to grow in Canada, more region-specific research may emerge to better address the nuances of patient care within the country.

Who Should Consider Bempedoic Acid?

Bempedoic acid offers a valuable treatment option for specific groups of patients who need to lower their LDL cholesterol but may not respond well to other therapies. This section will explore the types of patients who might benefit most from bempedoic acid, as well as the considerations healthcare providers in Canada should take into account when prescribing it.

Patients with Statin Intolerance One of the most prominent groups for whom bempedoic acid may be beneficial are those who experience statin intolerance. Statins, while effective, can cause muscle-related side effects such as myalgia (muscle pain) and myopathy (muscle weakness) in a subset of patients. These side effects can lead to reduced adherence to therapy or discontinuation altogether. For patients who are unable to tolerate even low doses of statins, bempedoic acid presents a non-statin oral option that can effectively lower LDL cholesterol without triggering these muscle-related side effects, making it a safer alternative for this population.

Patients with Familial Hypercholesterolemia Bempedoic acid is also a suitable option for individuals with familial hypercholesterolemia (FH), a genetic condition that leads to extremely high levels of LDL cholesterol from a young age. These patients often require more aggressive LDL-lowering treatments. While statins are typically first-line therapy, bempedoic acid can be added to their regimen for further reduction in LDL cholesterol, particularly when statins alone are insufficient or poorly tolerated.

Patients Needing Additional LDL Reduction Even patients who do not have statin intolerance may benefit from bempedoic acid if they require additional LDL reduction beyond what is achieved with statins alone. In such cases, bempedoic acid can be combined with statins or ezetimibe to produce additive effects, further lowering LDL cholesterol without the need to increase the statin dose, which could worsen side effects.

Older Adults Older adults often have higher rates of statin intolerance due to age-related muscle and joint conditions. This makes bempedoic acid an appealing option for managing cholesterol in older populations who still need LDL-lowering therapy but want to avoid the discomfort or risks associated with higher-dose statins. The safety profile of bempedoic acid, with fewer muscle-related issues, makes it especially attractive for this demographic.

Access to Bempedoic Acid in Canada

As bempedoic acid gains traction as an LDL-lowering therapy, its availability in Canada continues to grow. However, access to this medication can depend on several factors, including provincial healthcare coverage, private insurance plans, and the cost of the medication. This section will explore how Canadians can access bempedoic acid and what they should consider when discussing treatment options with their healthcare providers.

Availability Across Canada Bempedoic acid is approved by Health Canada and is available under the brand name Nexletol™. It can be prescribed by healthcare providers across the country, but access may vary depending on the province or territory in which a patient resides. As with many prescription medications, coverage for bempedoic acid under public health plans differs between provinces. Some provinces may have already included bempedoic acid on their formularies, while others may require a case-by-case review or restrict its use to specific patient populations, such as those with statin intolerance or familial hypercholesterolemia.

Private Insurance Coverage For patients with private insurance, coverage for bempedoic acid often depends on the specifics of their plan. Many insurance companies are beginning to add bempedoic acid to their list of covered medications, particularly as awareness of the drug increases and more patients seek alternatives to statins. Patients with private insurance should consult their provider to determine if bempedoic acid is covered and what the out-of-pocket costs may be. In some cases, physicians may need to submit special authorization requests, especially for patients who do not meet typical statin intolerance criteria.

Cost of Bempedoic Acid Without insurance coverage, the cost of bempedoic acid can be significant, making it important for patients to explore their options for coverage. The retail price for a one-month supply of bempedoic acid (usually 180 mg daily) can range in cost, but it typically falls in the range of several hundred dollars. Given its relatively high cost compared to generic statins, patients and healthcare providers often weigh the benefits of bempedoic acid against these financial considerations, particularly when other cholesterol-lowering options are available.

Navigating Provincial Health Plans In the Canadian healthcare system, each province and territory operates its own public drug plan, which may cover medications for specific groups, such as seniors, those with low incomes, or individuals with certain medical conditions. For bempedoic acid, patients may need to meet certain criteria to be eligible for public coverage, such as proven intolerance to statins or a diagnosis of familial hypercholesterolemia. Patients are encouraged to speak with their healthcare provider and pharmacist to understand the steps involved in accessing bempedoic acid through their provincial plan.

Patient Assistance Programs To help reduce the financial burden, some pharmaceutical companies offer patient assistance programs for individuals who may struggle to afford bempedoic acid. These programs often provide discounts or co-pay assistance for those who qualify, making the medication more accessible to a broader range of patients. Healthcare providers can offer guidance on how to apply for these programs and help determine eligibility.

Conclusion

Bempedoic acid is emerging as a vital tool in the fight against elevated LDL cholesterol, particularly for individuals who cannot tolerate statins or require additional therapy to achieve their cholesterol goals. Its unique mechanism of action, which targets cholesterol synthesis specifically in the liver, allows it to reduce LDL cholesterol without causing the muscle-related side effects that often limit the use of statins. This makes bempedoic acid a valuable option for patients who have struggled to manage their cholesterol levels with existing therapies.

As awareness of bempedoic acid continues to grow, it provides new hope for many Canadians in achieving healthier cholesterol levels and reducing their risk of cardiovascular disease. With the right guidance and support, bempedoic acid can help patients achieve their cholesterol goals while minimizing the side effects that may have limited their options in the past.

FAQ

Does bempedoic acid reduce triglycerides?

Bempedoic acid primarily targets LDL cholesterol but does not significantly reduce triglycerides. Its main action is on lowering LDL cholesterol, and any effects on triglycerides are minimal and inconsistent.

How long has bempedoic acid been around?

Bempedoic acid was approved by the FDA in February 2020, making it relatively new to the market. It was introduced as an additional option for lowering LDL cholesterol in patients who are either intolerant to statins or need additional LDL reduction beyond what statins provide.

Who should not take bempedoic acid?

Bempedoic acid should not be taken by individuals with severe liver disease, those who are pregnant or breastfeeding, or people with a known hypersensitivity to the drug. It should also be used cautiously in individuals with moderate liver impairment or those at risk of tendon rupture.

Does bempedoic acid cause weight gain?

Bempedoic acid is not commonly associated with weight gain. Its primary side effects include muscle spasms, increased uric acid levels, and tendon issues, but weight gain is not typically reported as a concern.

Can bempedoic acid cause kidney problems?

Bempedoic acid has not been widely associated with causing kidney problems. However, it can raise uric acid levels, potentially leading to gout or worsening existing kidney issues related to uric acid buildup. Patients with pre-existing kidney conditions should consult their healthcare provider before using bempedoic acid.

Does bempedoic acid cause gout?

Yes, bempedoic acid can increase uric acid levels, which may lead to the development of gout or exacerbate existing gout in some patients. This is one of the noted side effects, so individuals with a history of gout should use it cautiously and under medical supervision.

Does bempedoic acid raise blood sugar?

Bempedoic acid is not commonly associated with raising blood sugar levels. However, in some cases, slight increases in blood sugar have been observed, particularly in patients who are at risk for or have type 2 diabetes. Monitoring blood glucose levels may be advisable for these patients.

Disclaimer: This blog post is intended for educational purposes only and should not be taken as medical advice. Always consult your healthcare provider for personal health concerns.