Cardiovascular (CV) disease remains the leading cause of morbidity and mortality worldwide and poses an ongoing challenge with the aging population. Elevated low-density lipoprotein cholesterol (LDL-C) is an established risk factor for atherosclerotic cardiovascular disease (ASCVD), and the expert consensus is the use of statin therapy (if tolerated) as first line for LDL-C reduction. However, patients with ASCVD may experience recurrent ischemic events despite receiving maximally tolerated statin therapy, including those whose on-treatment LDL-C remains ≥70 mg/dL, patients with familial hypercholester-olemia, high-risk subgroups with comorbidities such as diabetes mellitus, and those who have an intolerance to statin therapy. Optimal therapeutic strategies for this unmet need should deploy aggressive lipid lowering to minimize the contribution of dyslipidemia to their CV risk, particularly for very high-risk populations with additional risk factors beyond hypercholesterolemia and established ASCVD. To understand the current clinical climate and guidelines regarding ASCVD, we primarily searched PubMed for articles published in English regarding lipid-lowering therapies and CV risk reduction, including emerging thera-pies, and CV outcomes trials with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. This review discusses the findings of recent clinical trial evidence for CV risk reduction with cholesterol-lowering therapies, with a focus on CV outcomes trials with PCSK9 inhibitors, and considers the impact of the study results for secondary prevention and future strategies in patients with hypercholesterolemia and CV risk despite maximally tolerated statin therapy.
Bibliographical noteFunding Information:
Employees of Sanofi and Regeneron Pharmaceuticals, Inc., were permitted to review the manuscript and offer comments. However, the authors were responsible for all content and editorial decisions. Dr Duprez has received clinical trial support from Regeneron Pharmaceuticals, Inc., AstraZeneca, and Esperion. Dr Handelsman has received research grants, and consultant and speaker honoraria from Amarin, Amgen, Applied Therapeutic, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Boehringer Ingelheim-Eli Lilly and Company alliance, Esperion, Gan & Lee, Gilead, Janssen, Merck, Mylan, Merck-Pfizer, Novo Nordisk A/S, and Sanofi; and reports non-financial support from Sanofi, during the conduct of the study; grants and personal fees from Amgen and Novo, grants, personal fees, and non-financial support from Astrazeneca and Sanofi, and personal fees from Esperion and Regeneron Pharmaceuticals, Inc., outside the submitted work. Dr Koren is an employee of a company that has received study grants and consulting fees from manufacturers of PCSK9 inhibitors and treatments for lipid disorders. The authors report no other potential conflicts of interest for this work.
Medical writing assistance and editorial support, under the direction of the authors, was provided by Nila Bhana, MSc, and Rob Campbell, PhD, of Prime, Knutsford, UK, funded by Sanofi and Regeneron Pharmaceuticals, Inc., according to Good Publication Practice guidelines (https://www .acp
© 2020 Duprez et al.
- Atherosclerotic cardiovascular disease
- Low-density lipoprotein cholesterol
- Major adverse cardiovascular events
- Secondary prevention