Cost-effectiveness of PCSK9 Inhibitors

Abstract

In recent weeks, JAMA and JAMA Cardiology have published 3 separate cost-effectiveness analyses of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor drug evolocumab, 1-3 each of which addresses the value proposition of this innovative but expensive therapy for reducing lowdensity lipoprotein cholesterol levels. These 3 analyses are timely in the wake of the Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) trial, 4 which demonstrated that the addition of evolocumab to baseline statin therapy resulted in significant reductions, compared with placebo, in cardiovascular events in highrisk secondary prevention patients. In 2 instances, the reports represent updates of analyses that predated the FOURIER results. 1,3 Following the first update by Kazi et al, 1 the editors undertook extensive discussion and decided to publish the next 2 analyses, 2,3 although cognizant of the risks of appearing to disseminate repetitive findings. In addition to the value of publishing confirmatory results, we determined that these 3 analyses, when viewed collectively, would provide our readers with insights into the nuances of interpreting and understanding cost-effectiveness studies.As noted in the insightful editorials 5,6 that followed the reports by Kazi et al 1 and Fonarow et al, 2 the cost-benefit models used by the investigators determine the outcomes of costeffectiveness studies, and the assumptions that are incorporated into those models also heavily influence results. Although the different scenarios developed in these 3 reports yield quantitatively different values of the projected incremental costeffectiveness ratio (ICER), which represents the incremental health care costs per gained quality-adjusted life-year (QALY), the bottom lines are qualitatively similar. Kazi et al 1 simulated 8.9 million individuals who met the FOURIER treatment criteria and reported an ICER of $450 000 per QALY. Using a Markov cohort state transition model that integrated US populationspecific demographics and risk factors, Fonarow et al 2 estimated an ICER between $268 600 and $413 000 per QALY, depending on the population. In the current issue of JAMA Cardiology, Arrieta et al 3 report an analysis of another Markov model over a lifetime horizon, based on observed rates of events,

Reformulating Small Molecules for Cardiovascular Disease Immune Intervention: Low-Dose Combined Vitamin D/Dexamethasone Promotes IL-10 Production and Atheroprotection in Dyslipidemic Mice

“…First, safety issues such as immunosuppression that might increase the susceptibility to infections and tumors (8,31). And second, the high costs [for example of biological drugs; (32,33)] and the logistic and technical limitations [for example of cellular therapies; (34)] that make unrealistic the translation of the agents to routine prophylactic or therapeutic clinical use.…”

Management of Dyslipidemia in Type 2 Diabetes: Recent Advances in Nonstatin Treatment

“…The efficacy and safety of evolocumab and alirocumab in FOURIER [ 18 ] and ODYSSEY Outcomes [ 19 ] are very promising, but with a hefty price tag of $14,000 per year in the United States. Three cost-effectiveness analyses [ 45 , 46 , 47 ] incorporating data from FOURIER have been reported, with an incremental cost-effectiveness ratio (ICER) of $268,600 to $450,000 per quality-adjusted life-year (QALY), and a 60% to 70% reduction from current prices would be needed to achieve a societally acceptable ICER of $100,000 per QALY [ 48 ].…”

CVD Risk Stratification in the PCSK9 Era: Is There a Role for LDL Subfractions?

“…Very high risk patients are usually defined as patients with familial hypercholesterolemia (FH), in secondary prevention for patients with high residual risk after statin therapy, or patients who do not tolerate appropriate doses of statins. Currently, individuals without FH in primary prevention do not fulfil cost-effectiveness criteria due to the high costs of these new drugs [ 47 , 48 ].…”