Novel Lipid Therapies: 5 Things to Know

Alan P. Jacobsen, MB, BCh, BAO; Eamon Y. Duffy, MD, MBA; Seth S. Martin, MD, MHS

June 23, 2020

Editorial Collaboration

Medscape &

The development of novel pharmacotherapies targeting low-density lipoprotein (LDL), lipoprotein a, and triglycerides (TG) to help prevent patients' risk of atherosclerotic cardiovascular disease (ASCVD) has accelerated during the past decade. Some of these therapies have been approved as an adjunct to primary dyslipidemia therapies. Major societal guidelines, including those from the American College of Cardiology/American Heart Association (ACC/AHA) and the European Society of Cardiology/European Atherosclerosis Society (ESC/EAS), continue to recommend the highest tolerated statin as first-line therapy to lower LDL levels, as well as the addition of ezetimibe for patients considered to be at very high risk for ASCVD. In addition to these recommendations, the ACC/AHA and ESC/EAS guidelines now support the use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors to reduce patients' LDL levels and risk for ASCVD.

There are multiple additional therapies to discuss. Clinical outcomes data now support the use of a high-dose, highly purified form of omega-3 fatty acid, eicosapentaenoic acid (EPA), for patients with elevated TG levels. Furthermore, several novel therapies with innovative mechanisms to target hepatocytes and minimize off-site adverse effects have shown promising results in phase 3 trials, with clinical outcomes data on the horizon.

Here are five things to know about novel lipid therapies.

1. Physicians should consider a PCSK9 inhibitor as an add-on therapy to statin plus ezetimibe regimens in patients whose LDL levels remain above the targeted goal.

The PCSK9 protein promotes the degradation of the LDL receptor, resulting in diminished clearance of LDL from the bloodstream. The PCSK9 inhibitors alirocumab and evolocumab are monoclonal antibodies that target the PCSK9 protein and increase LDL receptor activity, and they have been shown to decrease circulating LDL levels by an average of 60%.

The ODYSSEY OUTCOMES and the FOURIER trials were two large randomized controlled trials of patients with clinical ASCVD who, despite statin therapy, had baseline LDL levels ≥ 70 mg/dL. The ODYSSEY OUTCOMES trial demonstrated a 15% relative reduction (absolute risk reduction [ARR], 1.6%) of cardiovascular (CV) events in patients receiving alirocumab during a median follow-up of 2.8 years. Similarly, in the FOURIER trial, evolocumab significantly reduced the risk primary composite outcome by 15% (hazard ratio, 0.85; 95% CI, 0.79-0.92; P < .001; ARR, 1.59%) during a median follow-up of 2.2 years.

Although the ESC/EAS and AHA/ACC support the use of PCSK9 inhibitors, the class of recommendation/strength of recommendation differs between the two guidelines. Although the ESC/EAS guidelines outline a more aggressive strategy regarding the use of PCSK9 inhibitors in patients with ASCVD, the strength of recommendation for use of PCSK9 inhibitors in the AHA/ACC guidelines is based on concerns over the cost-benefit ratio (which continues to be an issue despite a 60% reduction in the cost of these drugs). The current AHA/ACC guidelines recommend considering PCSK9 inhibitors in patients striving to have optimal LDL control (LDL level ≥ 70 mg/dL for very high-risk secondary prevention or LDL level ≥ 100 mg/dL for high-risk primary prevention).

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