Bempedoic Acid: New Drug Is Game Changer

Heart Disease Fun Facts:  According to the CDC

• Every 34 seconds, someone dies of heart disease in the US.
• 697,000 people die annually of heart disease in the US. That's 1 out of 5 deaths.
• In 2017-2018, the cost of healthcare services, medication, and lost productivity due to heart disease totaled about $229 million.

Heart Disease and LDL

For the last thirty years, the statin class of drugs (HMG-CoA reductase inhibitors) remains one of the most widely used drugs. Drugs like atorvastatin, pravastatin, and simvastatin are given to reduce LDL (low-density lipids) and stabilize plaque on vessel walls. Statins are the standard for reducing arterial inflammation, and the risk of myocardial infarctions and strokes.

However, millions of patients suffer from statin intolerance due to myalgia, myopathy, and in severe cases, rhabdomyolysis, leaving them with few treatment options.

Alternatives and Adjuncts to Statins

CoQ10 is believed to alleviate the myalgia some patients experience when taking statins. Studies on the efficacy of CoQ10 have been promising but inconclusive.

Niacin is another cholesterol-reducing agent which causes many patients to have severe hot skin flushing and dizziness.

Red rice yeast is an alternative supplement some patients swear by, while others report it didn't lower their LDL at all.

Questran (cholestyramine) is a bile acid sequestrant that has been in use since the 1970s. Bile acid sequestrants are highly positively charged molecules that bind to negatively charged bile acids in the intestine, inhibiting their lipid solubilizing activity, and thus blocking cholesterol absorption.

Zetia (Ezetimibe) is a cholesterol absorption inhibitor that performs well to lower cholesterol when combined with a statin (simvastatin) =Vytorin.  Although, trials showed that ezetimibe combined with statins didn't have much effect on heart-related death.

Praluent (alirocumab) & Repatha (evolocumab) PCSK9 Inhibitors are a new class of LDL-reducing drugs. The route is by injection, and many patients do not like to self-inject.

Bempedoic acid (ATP citrate lyase inhibitor). An alternate choice became available when bempedoic acid was approved by the FDA in February 2020. At the time, bempedoic acid was meant to be used as an adjunct with statins, it was unclear whether the drug was associated with a reduced risk of a major adverse cardiovascular event (MACE).

Major adverse cardiovascular events include death from cardiovascular causes, nonfatal myocardial infarction, nonfatal cerebrovascular accident, and coronary revascularization.

CLEAR OUTCOMES Trial

On March 4, the CLEAR OUTCOMES Trial, presented at the annual American College of Cardiology 23/WCC (World Congress of Cardiologists) in New Orleans, revealed that in patients with statin intolerance, bempedoic acid was associated with a lower risk of major adverse cardiovascular events.

According to Steven E. Nissen, MD, MACC, the chief academic officer of the Heart Vascular and Thoracic Institute at Cleveland Clinic and chair of the study, "Most people can take statins, but some cannot. This is the first study that directly addressed the problem of statin-intolerant patients. We achieved what we hoped we would get – a very positive result in a population of people who just could not tolerate statins."

Given that heart disease remains the number one killer of men and women, clinicians need more treatment options to offer patients. It's difficult to get patients to comply with these treatments if they have uncomfortable side effects. And that may have a negative impact on their outcomes.

Bempedoic Acid Overview

The CLEAR OUTCOMES Trial showed that bempedoic acid lowered study participants' LDL cholesterol by 20%-25% on average throughout the study. Participants taking a placebo saw an average of 10% reduction in LDL, which demonstrates closer monitoring and the addition of other cholesterol-reducing agents as part of their background therapy, according to researchers.

Bempedoic acid is not without side effects. Participants experienced renal impairment, gout, gallstones, and elevated hepatic enzymes. Nevertheless, side effects didn't indicate discontinuation of the drug.

As a rule, statins reduce LDL by about 40-50%, suggesting that bempedoic acid is not as effective at reducing cholesterol as statins or other drugs such as PCSK9 inhibitors (Praluent, Repatha). Moreover, the study determines that this measure of change can still make a difference in the risk of cardiac events for patients who cannot take statins.

Bempedoic acid may be prescribed under the brand name Nexletol and is manufactured by Esperion Therapeutics. A one-month supply costs about $400. Insurance companies need to consider that the cost of not taking this medication could greatly outweigh the expense of taking it when factoring in the cost of a hospital course for an MI or stroke.

When patients are:

• Non-compliant with their disease management.
• Do not take their medications.
• Blow off follow-up appointments.
• Continue to smoke with freshly deployed drug-eluting stents in their major coronary arteries, 

The risk of MACE increases.

Many patients report that they cannot or will not take their prescribed statin because it gives them terrible life-altering discomfort. These are patients who:

• have had multiple MIs
• have multiple stents
• have CABG
• are already at risk for additional major adverse cardiovascular events. 

Recall the fact I shared above; the cost of health care services, medications, and lost productivity secondary to heart disease totals about $229 million annually. As advances in technology and new therapies are discovered, clinicians can offer patients alternative options. Offering alternatives keeps patients compliant and reduces their overall risk of a major cardiac event. Bempedoic acid bears a two-fold benefit in that it can contribute to cost reduction and reduce the risk of MACE. 

References/Resources

Bempedoic Acid Improves Outcomes in Statin-Intolerant Patients: American College of Cardiology Foundation

Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients: The New England Journal of Medicine

Heart Disease Facts: Centers for Disease Control and Prevention

Ezetimibe for the prevention of cardiovascular disease and all‐cause mortality events: National Center for Biotechnology Information: National Library of Medicine

What is Atherosclerosis? - Atherosclerosis and cholesterol: American Heart Association, Inc.

Ezetimibe: National Center for Biotechnology Information: National Library of Medicine