At its current list price of $14 523, the addition of evolocumab to standard background therapy in patients with atherosclerotic cardiovascular disease exceeds generally accepted cost-effectiveness thresholds. To achieve an ICER of $150 000 per QALY, the annual net price would need to be substantially lower ($9669 for US clinical practice and $6780 for trial participants), or a higher-risk population would need to be treated.

Randomized trials have shown marked reductions in low‐density lipoprotein cholesterol (LDL‐C), a risk factor for cardiovascular disease (CVD), when evolocumab is administered. We hypothesized that evolocumab added to standard of care (SOC) vs SOC alone is cost‐effective in the treatment of patients with heterozygous familial hypercholesterolemia (HeFH) or atherosclerotic CVD (ASCVD) with or without statin intolerance and LDL‐C >100 mg/dL. Using a Markov cohort state transition model, primary and recurrent CVD event rates were predicted considering population‐specific trial‐based mean risk factors and calibrated against observed rates in the real world. The LDL‐C–lowering effect from population‐specific phase 3 randomized studies for evolocumab was used together with estimated LDL‐C–lowering effect on CVD event rates per 38.67‐mg/dL LDL‐C lowering from a statin‐trial meta‐analysis. Costs and utilities were included from published sources. Evolocumab treatment was associated with both increased cost and improved quality‐adjusted life‐years (QALY): HeFH (incremental cost: US$153 289, incremental QALY: 2.02, incremental cost‐effectiveness ratio: US$75 863/QALY); ASCVD (US$158 307, 1.12, US$141 699/QALY); and ASCVD with statin intolerance (US$136 903, 1.36, US$100 309/QALY). Evolocumab met both the American College of Cardiology/American Heart Association (ACC/AHA) and World Health Organization (WHO) thresholds in each population evaluated. Sensitivity and scenario analyses confirmed that model results were robust to changes in model parameters. Among patients with HeFH and ASCVD with or without statin intolerance, evolocumab added to SOC may provide a cost‐effective treatment option for lowering LDL‐C using ACC/AHA intermediate/high value and WHO cost‐effectiveness thresholds. More definitive information on the clinical and economic value of evolocumab will be available from the forthcoming CVD outcomes study.

cholesterol management guideline was released. An updated cost-effectiveness analysis of evolocumab in the United States may be therefore of interest to payers and prescribers. OBJECTIVE To present an updated cost-effectiveness analysis of evolocumab added to standard background therapy compared with standard background therapy alone in patients with very high-risk atherosclerotic cardiovascular disease, reflecting the 2018 ACC/AHA guideline definition and using the new evolocumab list price. DESIGN, SETTING, AND PARTICIPANTS This study used the Markov model originally used in a previous study by Fonarow et al in 2017. A US societal perspective was considered, and a range of baseline cardiovascular event rates were modeled to reflect varying risk profiles in clinical practice within patients with very high-risk atherosclerotic cardiovascular disease. EXPOSURES Addition of evolocumab to standard background therapy, including maximally tolerated statin therapy (ie, the maximum intensity of statin therapy a patient can safely receive), with or without ezetimibe. MAIN OUTCOMES AND MEASURES Major cardiovascular events (myocardial infarction, ischemic stroke, and cardiovascular death), costs, quality-adjusted life-years, and incremental cost-effectiveness ratios. RESULTS Evolocumab was associated with both increased costs and improved outcomes when added to standard background therapy. Incremental costs ranged from $22 228 to $3411, depending on the varying level of risk within the defined population. Incremental quality-adjusted life years ranged from 0.39 to 0.44. Incremental cost-effectiveness ratios ranged from $56 655 to $7667 per quality-adjusted life-year gained. For a range of baseline cardiovascular event rates in patients with very high-risk atherosclerotic cardiovascular disease, incremental cost-effectiveness ratios were below the generally accepted willingness-to-pay thresholds. Moreover, the ratios were below the threshold of $50 000 per quality-adjusted life-years gained for any baseline rate of 6.9 or more events per 100 patient-years. CONCLUSIONS AND RELEVANCE At its current list price, the addition of evolocumab to standard background therapy meets accepted cost-effectiveness thresholds across a range of baseline cardiovascular event rates in patients with very high-risk atherosclerotic cardiovascular disease as defined by the 2018 ACC/AHA guideline.

Aim: To estimate real-world cardiovascular disease (CVD) burden and value-based price range of evolocumab for a US-context, high-risk, secondary-prevention population. Materials and methods: Burden of CVD was assessed using the UK-based Clinical Practice Research Datalink (CPRD) in order to capture complete CV burden including CV mortality. Patients on standard of care (SOC; high-intensity statins) in CPRD were selected based on eligibility criteria of FOURIER, a phase 3 CV outcomes trial of evolocumab, and categorized into four cohorts: high-risk prevalent atherosclerotic CVD (ASCVD) cohort (n ¼ 1448), acute coronary syndrome (ACS) (n ¼ 602), ischemic stroke (IS) (n ¼ 151), and heart failure (HF) (n ¼ 291) incident cohorts. The value-based price range for evolocumab was assessed using a previously published economic model. The model incorporated CPRD CV event rates and considered CV event reduction rate ratios per 1 mmol/L reduction in low-density lipoprotein-cholesterol (LDL-C) from a meta-analysis of statin trials by the Cholesterol Treatment Trialists Collaboration (CTTC), i.e. CTTC relationship. Results: Multiple-event rates of composite CV events (ACS, IS, or coronary revascularization) per 100 patient-years were 12.3 for the high-risk prevalent ASCVD cohort, and 25.7, 13.3, and 23.3, respectively, for incident ACS, IS, and HF cohorts. Approximately one-half (42%) of the high-risk ASCVD patients with a new CV event during follow-up had a subsequent CV event. Combining these real-world event rates and the CTTC relationship in the economic model, the value-based price range (credible interval) under a willingness-to-pay threshold of $150,000/quality-adjusted life-year gained for evolocumab was $11,990 ($9,341-$14,833) to $16,856 ($12,903-$20,678) in ASCVD patients with baseline LDL-C levels !70 mg/dL and !100 mg/dL, respectively. Conclusion: Real-world CVD burden is substantial. Using the observed CVD burden in CPRD and the CTTC relationship, the cost-effectiveness analysis showed that, accounting for uncertainties, the expected value-based price for evolocumab is higher than its current annual cost, as long as the payer discount off list price is greater than 20%. ARTICLE HISTORY

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