Introduction: In the United States, a significant amount of the population is affected by hyperlipidemia, which is associated with increased levels of serum low-density lipoprotein (LDL-C) and risk of cardiovascular disease. As of 2019, the guidelines set by the American College of Cardiology/American Heart Association advocate for the use of statins as the major contributor to lowering serum LDL-C. While proven to be effective, side effects, including muscle-related symptoms and new-onset diabetes mellitus, can make patients unable to tolerate statin therapy. Additionally, there is a subset of the population which does not approach a recommended LDL-C goal on statin treatment. Due to these findings, it was deemed necessary to review the literature of current statin-alternative lipid-lowering therapies.
Methods: A systematic review of preclinical and clinical papers, and a current meta-analysis, was performed using PubMed and Google Scholar. Following the literature review, a meta-analysis was conducted using ProMeta 3.
Results: Through systematic review and meta-analysis of the current literature, it is suggested that newer lipid-lowering therapies such as proprotein convertase subtilsin-kixen type 9 (PCSK9) inhibitors are a safe and effective statin alternative for the population with statin intolerance. PCSK9 inhibitors were shown to have no significant effect in causing myalgia in patients and showed no increase in adverse cardiovascular outcomes compared to a control of a current antilipemic medication regimen.
Discussion: There are many statin-alternative therapies that should be investigated further as a potential replacement for patients with statin intolerance or as an addition for patients with statin resistance.
Keywords: 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA); cardiovascular; hyperlipidemia; low-density lipoprotein; proprotein convertase subtilsin-kixen type 9 inhibitor (PCSK9i); statin intolerance; statin resistance; statin-associated muscle symptoms (SAMS).