Background: Nonstatin costs and uncertainty about benefits currently limit their use. Estimation of the potential for net benefit may better guide the addition of nonstatin therapy.
Objective: Identify groups of patients who might benefit from the addition of a nonstatin to background statin therapy.
Methods: Systematic reviews of subgroup analyses from randomized trials and observational studies were used to determine the estimated 10-year absolute risk of atherosclerotic cardiovascular disease (ASCVD) to define high and very high risk patient groups. Calculated relative risk reductions for the addition of a nonstatin were used to determine the number-needed-to-treat to prevent one ASCVD event (NNT)over 5 years for each patient group to allow comparisons to 5-year cost analyses. Number-needed-to-harm and net benefit were evaluated.
Results: 10-year ASCVD risk for statin-treated participants with clinical ASCVD with comorbidities is at least 30% (very high risk), and 20-29% (high risk) for those with ASCVD without comorbidities or who have heterozygous familial hypercholesterolemia. Adding ezetimibe to reduce 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 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/d. From the payer’s perspective, PCSK9 mAbs may be cost effective in very high risk and high risk patients depending on the baseline LDL-C level and magnitude of discounting.
Conclusions: Quantitative guidance is provided to determine the potential for a net benefit over 5 years from adding ezetimibe or a PCSK9 mAb to maximally tolerated statin therapy from the perspective of clinicians, patients, and payers.