PCSK9 inhibitor valuation: A science-based review of the two recent models

Low-density lipoprotein cholesterol (LDL-C) has been extensively evaluated. Prospective cohort studies, randomized controlled trials, biology, pathophysiology, genetics, and Mendelian randomization studies, have clearly taught us that LDL-C causes atherosclerotic cardiovascular disease. The newest class of drugs to lower LDL-C, the proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies, have been found to safely reduce LDL-C approximately 60% when added to high-intensity statin therapy. Because their cost is much greater than that of the currently available agents, their value has been questioned. In late August, 2017, two groups assessed the value of this class of drugs looking at cost-effectiveness; however, the Institute for Clinical and Economic Review and Fonarow and colleagues found disparate results when assessing PCSK9 valuation. Herein, we review the evolution of LDL-C from hypothesis to fact, and then attempt to adjudicate the 2 models, shedding light on the complex modeling process. We find that models of cost-effectiveness are helpful adjuncts to decision making, but that their conclusions depend on many assumptions. Ultimately, clinician judgment regarding their clinical benefit, balanced by some estimation of cost, may be more productive to target the right patients for whom the benefits can be well-justified.