Determining When to Add Nonstatin Therapy

Study Questions:

Which patients might benefit from the addition of a nonstatin to background statin therapy?


The authors conducted a systematic review of subgroup analyses from randomized trials and observational studies to determine estimated 10-year absolute risk of atherosclerotic cardiovascular disease (ASCVD) and to define high- and very high-risk patients. The relative risk reductions for the addition of a nonstatin were used to determine the number needed to treat (NNT) to prevent one ASCVD event over 5 years for each patient group and to allow comparisons with 5-year cost analyses.


Ten-year ASCVD risk is at least 30% (very high risk) for statin-treated participants with clinical ASCVD and comorbidities, and 20-29% (high risk) for those with ASCVD without comorbidities or who have heterozygous familial hypercholesterolemia. Adding ezetimibe to reduce low-density lipoprotein cholesterol (LDL-C) by 20% would provide a 5-year NNT ≤50 for very high-risk patients with LDL-C ≥130 mg/dl or high-risk patients with LDL-C ≥190 mg/dl, and an NNT ≤30 for very high-risk patients with LDL-C ≥160 mg/dl. Adding a proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody (mAb) to lower LDL-C by at least 50% would provide an NNT ≤50 for very high- and high-risk patients with LDL-C ≥70 mg/dl, and an NNT ≤30 for very high- and high-risk patients with LDL-C ≥130 mg/dl.


Adding ezetimibe or PCSK9 mAbs to maximally tolerated statin therapy may be cost-effective in very high-risk and high-risk patients, depending on baseline LDL-C levels.


This is an incredibly exhaustive review that can support guidelines, be used in discussion with insurance carriers, and support present clinical practice patterns. The PCSK9 antibody therapy that lowers LDL-C more than 2 times that of ezetimibe may be more cost-effective at the present retail price of $10 per day than the latter in my region.

Clinical Topics: Dyslipidemia, Prevention, Lipid Metabolism, Nonstatins, Novel Agents, Primary Hyperlipidemia, Statins

Keywords: Atherosclerosis, Cholesterol, LDL, Comorbidity, Cost-Benefit Analysis, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hyperlipoproteinemia Type II, Numbers Needed To Treat, Physician's Practice Patterns, Primary Prevention, Proprotein Convertases, Risk, Subtilisins

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