Trends in Hyperlipidemia Treatments: Summary of Recommendations for Statin and Non-Statin Options

Review Article

J Fam Med. 2023; 10(5): 1343.

Trends in Hyperlipidemia Treatments: Summary of Recommendations for Statin and Non-Statin Options

Schultz PA¹*; Chaudhri P¹; Szymanski K¹; Landis E²; Snyder J²

¹Department of Family Medicine, The University of Toledo, USA

²Physician Assistant Studies – Dept of Family Medicine, The University of Toledo, USA

*Corresponding author: Schultz PA Department of Family Medicine, University of Toledo, 3333 Glendale Ave., Toledo, OH 43614, USA. Tel: 419-383-5522; Fax: 419-383-3113 Email: [email protected]

Received: November 21, 2023 Accepted: December 18, 2023 Published: December 23, 2023


Several treatment options and recommendations exist to guide a primary care provider to reduce overall cardiac morbidity and mortality risk through lipid control. The wealth of data from large studies, the choices of agents with varying mechanisms of action, and differing guidelines result in a challenge to keep abreast of this rapidly changing landscape. In this literature review the latest data regarding lipid management are reviewed and summarized. Current US and international cholesterol treatment guidelines recommend lifestyle modification followed by statin as first-line of therapy in management of hyperlipidemia. After optimizing statin dose if LDL remains above target goal, then the addition of ezetimibe provides added reductions in morbidity and mortality. Fibrates can be considered as an adjunct to statins therapy particularly in the diabetic population with persistent triglyceride elevations and provide modest reductions in coronary artery disease. PCSK9 inhibitors can reduce morbidity and mortality in a high-risk population when a statin or statin+ezetimibe does not bring LDL below the target goal. Some newer agents (ANGPTL3/ACL/MTP Inhibitors) are reserved for patients with a predisposition to ASCVD due to a familial genetic dyslipidemia. Cost for these adjunctive therapies is a concern for the patient and clinician and patient education along with a shared decision approach are warranted. To date, evidence for these agents is limited. Finally, there remains unclear guidance on the value between a “treat to dose” versus a “treat to target” approach to lipid management. Further research is needed to provide clarity on which strategy proves optimal for primary prevention of MACEs.

Keywords: Lipids; Statin; Fibrate; Coronary Artery Disease; Familial Hyperlipidemia; Major Adverse Cardiac Event; Coronary Artery Disease; ASCVD; Ischemic Heart Disease; Evinacumab; Cholestyramine; Colestipol; Colesevelam; Ezetimibe; Gemfibrozil; Fenofibrate; Fenofibric acid; Atorvastatin; Fluvastatin; Lovastatin; Pitavastatin; Pravastatin; Rosuvastatin; Evolocumab; Alirocumab; Bempedoic Acid; Lomitapide; Mipomersen

Abbreviations: ASCVD: Atherosclerotic Cardiovascular Disease; CAD: Coronary Artery Disease; ACS: Acute Coronary Syndrome; MI: Myocardial Infarction; MACE: Major Adverse Cardiac Event; SAMS: Statin Associated Muscle Symptoms; LDL-C: Low-Density Lipoprotein Cholesterol; HDL-C: High-Density Lipoprotein Cholesterol; Trigs: Triglycerides; EPA: Eicosapentaenoic Acid; DPA: Docosahexaenoic Acid; IPE: Icosapent Ethyl; OM3-FA: Omega-3 Fatty Acid; PCSK9: Proprotein Convertase Subtilisin/Kexin Type 9; ANGPTL3: Angiopoietin-Like Protein 3; ACL: Adenosine Triphosphate-Citrate Lyase; MTP: Microsomal Triglyceride Transfer Protein; RR: Relative Risk; NNT: Number Needed to Treat; NNTH: Number Needed to Harm; RCT: Randomized Controlled Trial; SORT: Strength of Recommendation Taxonomy; LOE: Level of Evidence; HoFH: Homozygous Familial Hypercholesterolemia; HeFH: Heterozygous Familial Hypercholesterolemia


Lipid disorders and Cardiovascular (CV) disease are a major cause of morbidity and mortality all over the world. Over the years, many different classes of lipid lowering medications have been developed and studied- alone and in combination, with the goal of improving lipid management and decreasing CV morbidity and death. This article offers an updated source for primary care physicians in lipid management. It looks at the varying lipid lowering guidelines and the different classes of medications available to manage hyperlipidemia. The evidence of lipid lowering medications in decreasing LDL-C (low density lipoprotein cholesterol) and effects on improving CV outcomes is also discussed. Finally, it provides further context to the debate between treating LDL-C to goal or target.

Even though multiple classes of lipid lowering medications exist, the use of 3-hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (“statin”) medications for overall reduction of cardiac-related morbidity and mortality are well documented through several landmark studies. As a result, the use of statins with lifestyle modifications is a foundation of current hyperlipidemia and cardiac risk reduction per guidelines such as the American College of Cardiology (ACC) /American Heart Association (AHA). Since guideline publication, further studies have evaluated the additive effects of non-statins to statins in secondary prevention of atherosclerotic cardiovascular disease (ASCVD) events, especially in those at very high risk. Several established non-statin medications can be considered as solo therapy or as adjunctive to a statin regimen. The recent development of more non-statin therapeutic agents provides more advanced options in the treatment of hyperlipidemia and the reduction of ASCVD risk.

Table 1 summarizes the major classes of lipid lowering medications, their mechanism of action, LDL lowering effects, major side effects and costs.