Evolocumab added to standard background therapy in patients with atherosclerotic cardiovascular disease (ASCVD) is not cost-effective when compared with generally accepted cost-effectiveness benchmarks, concluded Gregg C. Fonarow, MD, FACC, et al., in a study recently published in JAMA Cardiology.

The FOURIER trial reported that adding evolocumab to statin therapy – which lowers low-density lipoprotein cholesterol (LDL-C) by about 60 percent – reduced cardiovascular events in patients with ASCVD, but did not reduce all-cause or cardiovascular mortality in the first three years of follow-up.

The present analysis used efficacy data from the FOURIER trial and a simulation model to assess the cost-effectiveness of evolocumab added to standard therapy in clinical practice in patients with ASCVD. A Markov cohort state-transition model was used, with model transition-states adapted to match those analyzed in the FOURIER study. For the model base case, the investigators assumed a five-year delay before cardiovascular mortality reductions would emerge.

The list price of $14,523 was used for the cost of evolocumab in the base case. Analyses were also performed based on an estimated mean annual net cost of $10,311. The lifetime cost and quality-adjusted life-years (QALY) for evolocumab added to standard therapy (moderate- to high-intensity statin with or without ezetimibe) vs. standard therapy alone were projected through simulation. The incremental cost-effectiveness ratio (ICER) was calculated as the incremental cost per QALY gained. The cost-effectiveness threshold of $150,000 per QALY gained was used. Sensitivity and scenario analyses were conducted.

In the base case, the LDL-C level was at least 70 mg/dl (mean, 104 mg/dl) and the cardiovascular event rate was 6.4 per 100 patient-years with standard therapy. Mean lifetime costs would be $234,877 for patients treated with standard therapy and $340,275 for patients treated with evolocumab added to standard therapy. The lifetime QALY was 7.23 with standard therapy and 7.62 with evolocumab. The ICER for evolocumab was $268,637 per QALY gained when used at its list price and $165,689 per QALY when used at the net price. An annual value-based net price of $9,669 would be needed to achieve a value threshold of $150,000.

The authors concluded that a comprehensive disease management approach for ASCVD, including vigorous lifestyle changes, strict adherence to guideline-directed therapies and judicious use of new, more costly therapies is needed.

In a related editorial, Daniel B Mark, MD, MPH, FACC, et al., noted that two other studies in the past year reported that PCSK9 inhibitor therapy does not provide good value for the cost. "Unfortunately, things may be even less favorable than they seem," they said, claiming that several model assumptions are more optimistic than warranted. Although FOURIER found no effect on mortality, this study and others assumed a late survival benefit would emerge. Huge price reductions would be necessary if the long-term benefits of evolocumab were overestimated. Possible solutions include a "radical lowering of the price" or a "radical restriction of therapy to patients with a markedly elevated risk. Money spent on PCSK9 inhibitor therapy could be invested by health systems to make better use of the affordable drugs we already have," they concluded.

Keywords: Cholesterol, LDL, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Quality-Adjusted Life Years, Cost-Benefit Analysis, Benchmarking, Research Personnel, Follow-Up Studies, Antibodies, Monoclonal, Atherosclerosis, Risk, Disease Management, Life Style

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