Background Costs and uncertainty about the benefits of nonstatin therapies limit their use. Objectives The authors sought to identify patients who might benefit from the addition of a nonstatin to background statin therapy. Methods We performed systematic reviews of subgroup analyses from randomized trials and observational studies with statin-treated participants to determine estimated 10-year absolute risk of atherosclerotic cardiovascular disease (ASCVD) and to define high-risk and very high-risk patients. We used the relative risk reductions for the addition of a nonstatin to lower low-density lipoprotein (LDL-C) used to determine the number needed to treat (NNT) to prevent 1 ASCVD event over 5 years for each patient group and to allow comparisons with 5-year cost analyses. Results The 10-year ASCVD risk is at least 30% (very high risk) for statin-treated participants with clinical ASCVD and comorbidities, and 20% to 29% (high risk) for those with ASCVD without comorbidities or who have heterozygous familial hypercholesterolemia. Adding ezetimibe to reduce low-density LDL-C by 20% would provide a 5-year NNT ≤50 for very high-risk patients with LDL-C ≥130 mg/dl or for 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 PCSK9 monoclonal antibody to lower LDL-C by at least 50% would provide an NNT ≤50 for very high-risk and high-risk patients with LDL-C ≥70 mg/dl, and an NNT ≤30 for very high-risk and high-risk patients with an LDL-C ≥130 mg/dl. Conclusions Adding ezetimibe or PCSK9 monoclonal antibodies to maximally tolerated statin therapy may be cost effective in very high-risk and high-risk patients, depending on baseline LDL-C levels.
Robinson, J. G., Huijgen, R., Ray, K., Persons, J., Kastelein, J. J. P., & Pencina, M. J. (2016). Determining When to Add Nonstatin Therapy: A Quantitative Approach. Journal of the American College of Cardiology, 68(22), 2412–2421. https://doi.org/10.1016/j.jacc.2016.09.928