The oral adenosine triphosphate-citrate lyase (ACL) inhibitor bempedoic acid was approved by the FDA in 2020 for use alone (Nexletol – Esperion) and in a fixed-dose combination with the cholesterol absorption inhibitor ezetimibe (Nexlizet) as an adjunct to maximally tolerated statin therapy in adults with heterozygous familial hypercholesterolemia (HeFH) or established atherosclerotic cardiovascular disease (ASCVD) who require additional LDL-cholesterol (LDL-C) lowering. The indication has now been expanded to include reducing the risk of myocardial infarction (MI) and coronary revascularization in adults with established cardiovascular disease (CVD) or at high risk for a CVD event who are unable to take recommended statin therapy.

Since our initial review of the oral lipid-lowering adenosine triphosphate-citrate lyase (ACL) inhibitor bempedoic acid (Nexletol – Esperion) in 2020, cardiovascular outcomes data in statin-intolerant patients have become available.

Cholesterol management guidelines from the American College of Cardiology/American Heart Association Task Force were last published in 2019.

View the Comparison Table: Some Lipid-Lowering Drugs

The FDA has approved inclisiran (Leqvio – Novartis), a small interfering RNA (siRNA) directed to proprotein convertase subtilisin/kexin type 9 (PCSK9) mRNA, as an adjunct to diet and maximally tolerated statin therapy for subcutaneous (SC) treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (ASCVD) who require additional lowering of low-density lipoprotein cholesterol (LDL-C). Inclisiran is the first FDA-approved PCSK9-directed siRNA therapeutic agent.

The FDA has approved evinacumab-dgnb (Evkeeza – Regeneron), an angiopoietin-like 3 (ANGPTL3) inhibitor, for adjunctive IV treatment of homozygous familial hypercholesterolemia (HoFH) in patients ≥12 years old. Evinacumab is the first ANGPTL3 inhibitor to be approved in the US.

The FDA has approved the oral adenosine triphosphate-citrate lyase (ACL) inhibitor bempedoic acid for use alone (Nexletol – Esperion) and in a fixed-dose combination with the cholesterol absorption inhibitor ezetimibe (Nexlizet) as an adjunct to diet and maximally tolerated statin therapy in adults with heterozygous familial hypercholesterolemia (HeFH) or established atherosclerotic cardiovascular disease (ASCVD) who require additional lowering of LDL-cholesterol (LDL-C). Bempedoic acid is the first ACL inhibitor to be approved in the US.

Cholesterol management guidelines from the American College of Cardiology/American Heart Association Task Force have recently been published. See Table 1 for a brief summary of their recommendations.

The results of the recently published FOURIER trial have shown a reduction in cardiovascular events with addition of the PCSK9 inhibitor evolocumab (Repatha) to statin therapy in patients with atherosclerotic cardiovascular disease (ASCVD).

Lipid-lowering drugs should be taken indefinitely; when they are stopped, plasma lipoproteins return to pretreatment levels. HMG-CoA reductase inhibitors (statins) remain the drugs of choice for treatment of most patients who require lipid-lowering therapy.

The PCSK9 inhibitor evolocumab (Repatha – Amgen) is now available in a single-dose, hands-free device (Repatha Pushtronex) for once-monthly subcutaneous infusion. Evolocumab is FDA-approved as an adjunct to diet and maximally tolerated statin therapy for patients with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease who require additional lowering of low-density lipoprotein cholesterol (LDL-C), and as an adjunct to diet and other LDL-lowering therapies for patients with homozygous familial hypercholesterolemia (HoFH).

Evolocumab is also available in 140-mg single-use prefilled syringes and autoinjectors (Repatha Sureclick).1 Use of these formulations to administer the once-monthly dose (420 mg) requires patients to inject themselves three consecutive times within 30 minutes. Another PCSK9 inhibitor, alirocumab (Praluent), is injected every 2 weeks; it is available in single-dose prefilled syringes and pens.

The Repatha Pushtronex system consists of a single-use, battery-powered infusor and a prefilled cartridge containing a 420-mg dose of evolocumab. Once assembled, the patient adheres the device to the skin of the abdomen, thigh, or upper arm and presses a button to begin the subcutaneous injection; infusion of the dose takes about 9 minutes. One Repatha Pushtronex device costs $1175. Three 140-mg Repatha Sureclick autoinjectors or Repatha prefilled syringes cost $1627.2

1. Evolocumab (Repatha) – a second PCSK9 inhibitor to lower LDL-cholesterol. Med Lett Drugs Ther 2015; 57:140.
2. Approximate WAC for one 420-mg dose. WAC = wholesaler acquisition cost or manufacturer's published price to wholesalers; WAC represents a published catalogue or list price and may not represent an actual transactional price. Source: AnalySource® Monthly. August 5, 2016. Reprinted with permission by First Databank, Inc. All rights reserved. ©2016. www.fdbhealth.com/policies/drug-pricing-policy.

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Evolocumab (Repatha – Amgen), a subcutaneously injected PCSK9 inhibitor, has been approved by the FDA as an adjunct to diet and maximally tolerated statin therapy for adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease who require additional lowering of LDL-cholesterol (LDL-C). It was also approved as an adjunct to diet and other LDL-lowering therapies in patients with homozygous familial hypercholesterolemia (HoFH) who require additional lowering of LDL-C. Evolocumab is the second PCSK9 inhibitor to be approved in the US; alirocumab (Praluent) was approved earlier.

The FDA has approved the subcutaneously injected PCSK9 (proprotein convertase subtilisin kexin type 9) inhibitor alirocumab (Praluent – Sanofi/Regeneron) as an adjunct to diet and maximally tolerated statin therapy for adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease who require additional lowering of LDL-cholesterol (LDL-C). It was not approved for general use in statin-intolerant patients. Alirocumab is the first PCSK9 inhibitor to be approved in the US. Evolocumab (Repatha – Amgen), another PCSK9 inhibitor, was recently approved in Europe and has been recommended for approval for the same indications in the US by an FDA Advisory Committee.