Applicability and Cost Implications for Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors Based on the ODYSSEY Outcomes Trial
Authors: Salim S. Virani, Julia M. Akeroyd, Vijay Nambi, Erin D. Michos, Pamela B. Morris, Khurram Nasir, Sidney C. Smith, Neil J. Stone, Laura A. Petersen, Christie M. Ballantyne
Journal: Circulation (2019)

n the recently presented ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab trial, 1 alirocumab use in patients with acute coronary syndrome (ACS) and low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dL (or non-high-density lipoprotein cholesterol ≥100 mg/dL or apolipoprotein B ≥80 mg/dL) resulted in a 15% relative (1.6% absolute) reduction in the risk of major adverse cardiovascular events.We evaluated what proportion of patients in the VA Health Care System would qualify for alirocumab on the basis of ODYSSEY Outcomes criteria, how they are currently treated with LDL-C-lowering medications, and the cost implications if other evidence-based medications were used first before a proprotein convertase subtilisin/kexin type 9 inhibitor was considered.Using a national cohort, 2 we identified veterans with ischemic heart disease (with ACS or with a history of percutaneous coronary angiography or coronary artery bypass graft) receiving care in the VA system between October 1, 2014, and September 30, 2015 (n=1 015 971).We excluded 25 314 patients with metastatic cancer or those receiving hospice care.Among those remaining, 164 446 had a history of ACS.We excluded 154 104 patients using various ODYSSEY Outcomes trial exclusions (age <40 years, ACS <4 weeks before or >52 weeks after the index primary care visit, systolic blood pressure >180 mm Hg or diastolic blood pressure >110 mm Hg, history of hemorrhagic stroke, triglycerides >400 mg/dL, percutaneous coronary angiography or coronary artery bypass graft within 2 weeks, liver function test elevation >3 times the upper limit of normal, estimated glomerular filtration rate <30 mL•min -1 •m -2 or end-stage renal disease, use of gemfibrozil, or LDL-C<70 mg/dL and non-high-density lipoprotein cholesterol <100 mg/dL).The largest number of patients were excluded because of the diagnosis of ACS <4 weeks (n=18 605) or >52 weeks (n=130 770) from the index visit or because of LDL-C <70 mg/dL and non-high-density lipoprotein cholesterol <100 mg/dL (n= 7285).The protocol was approved by the Institutional Review boards at Baylor College of Medicine and the Michael E. DeBakey VA Medical Center.Of 10 342 patients who met inclusion criteria, 50.8% were on high-intensity, 28.5% were on moderate-intensity, and 5.3% were on low-intensity statins; 15.3% were not on a statin, whereas 1.3% were on ezetimibe.From pharmacy refill data, 43.5% had poor statin adherence (proportion of days covered <0.8).Assuming a 6% LDL-C reduction with each doubling of statin dose 3 and 20% LDL-C reduction with ezetimibe, 4 we calculated what proportion of these 10 342 patients will remain alirocumab eligible (LDL-C ≥70 mg/dL) after transition to high-intensity statin, added ezetimibe therapy, or a combination of high-intensity statin plus ezetimibe.Transition to high-intensity statin, ezetimibe, or a combination of highintensity statin plus ezetimibe would lead to 33%, 42.5%, and 65.3% of patients dropping their LDL-C levels to <70 mg/dL, with mean LDL-C levels of 57, 59, and 53 mg/dL, respectively, among those with LDL-C <70 mg/dL in each of the 3 scenarios.