Estimation of Eligibility for Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors and Associated Costs Based on the FOURIER Trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk)

I n the FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk), 1 treatment with evolocumab resulted in a 15% relative (1.5% absolute) risk reduction of major cardiovascular events in patients with atherosclerotic cardiovascular disease (ASCVD) at a median follow-up of 2.2 years.This trial included patients with low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dL or non-high-density lipoprotein cholesterol ≥100 mg/dL on at least moderate-intensity statins.It is not known what proportion of patients with ASCVD would qualify for evolocumab on the basis of FOURIER entry criteria and how eligibility would change if maximal doses of evidence-based lipid-lowering therapies were required.We assessed the number and proportion of US veterans with ASCVD who would qualify for evolocumab on the basis of FOURIER trial entry criteria and how these figures would change if high-intensity statins, ezetimibe, or the combination of both agents were used.Using a cohort of veterans with ASCVD (myocardial infarction, ischemic stroke, or peripheral arterial disease) receiving care in the Veterans Affairs (VA) system between October 2013 and September 2014, we identified all patients with ASCVD 40 to 85 years of age (n=631 855) using previously described algorithms with a positive predictive value of 88% in correctly identifying patients with ASCVD. 2 We identified patients meeting 1 major or 2 minor FOURIER protocol criteria and excluded patients with LDL-C <70 mg/dL or non-high-density lipoprotein cholesterol <100 mg/dL, those not receiving at least moderate-intensity statins, those with triglycerides >400 mg/dL, and those meeting other FOURIER exclusions. 1 Among patients meeting FOURIER inclusion and exclusion criteria, we determined proportions receiving moderate-intensity statins (30%-<50% LDL-C reduction), high-intensity statins (≥50% LDL-C reduction), 3 or a combination of moderate-or high-intensity statin and ezetimibe using VA pharmacy records.We then used 3 clinical scenarios to model how eligibility for evolocumab would change (on the basis of an LDL-C reduction to <70 mg/dL) if all patients were titrated to a high-intensity statin (assuming 6% LDL-C reduction with each statin dose doubling), ezetimibe use (assuming a 20% LDL-C reduction), 4 or a combination of high-intensity statin plus ezetimibe.Associated costs were estimated assuming a $0.07/d increment for titration to high-intensity statin, $2/d for the addition of generic ezetimibe, and $13 462.28/y for evolocumab.5 The protocol was approved by the Institutional Review boards at Baylor College of Medicine and the Michael E. DeBakey VA Medical Center.Among 631 855 patients with ASCVD who were 40 to 85 years of age, 154 823 (24.5%) would be evolocumab eligible with the use of FOURIER inclusion/exclusion criteria.The largest proportion were excluded because of LDL-C <70 or non-highdensity lipoprotein cholesterol <100 mg/dL (38.2%).However, only half (49.9%) of those who qualified were on high-intensity statins, whereas 47.5% were on moderate-intensity statins, and 2.6% were on a statin/ezetimibe combination.Mean