PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial

Raal, Frederick J.; Stein, Evan A.; Dufour, Robert; Turner, Traci; Civeira, Fernando; Burgess, Lesley; Langslet, Gisle; Scott, Russell; Olsson, Anders; Sullivan, David; Hovingh, G. Kees; Cariou, Bertrand; Gouni‐Berthold, Ioanna; Somaratne, Ransi; Bridges, Ian; Scott, Rob; Wasserman, Scott M.; Gaudet, Daniel

doi:10.1016/s0140-6736(14)61399-4

Cited by 657 publications

(546 citation statements)

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“…The patient population had an average age of 51 years, was 42.3% female, and had a mean LDL-C level of 155 mg/dL. These data are from the RUTHERFORD-2 trial [18]. Table 1 shows the detailed baseline characteristics of this HeFH population.…”

Section: Methodsmentioning

confidence: 99%

“…SD, standard deviation; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; SP, secondary prevention; CVD, cardiovascular disease; ECVD, established CVD; IS, ischaemic stroke; HF, heart failure; HeFH, heterozygous familial hypercholesterolaemia; MI, myocardial infarction* Imputed based on the REACH Registry (Wilson et al [32]) because of non-availability in RUTHERFORD-2 [18] † One or more fatal and non-fatal CVD event…”

Section: Methodsmentioning

confidence: 99%

“…* Imputed based on the REACH Registry (Wilson et al [32]) because of non-availability in RUTHERFORD-2 [18]…”

Section: Methodsmentioning

confidence: 99%

“…The predicted effectiveness of evolocumab on reducing CVD event rates is based on the relative LDL-C reduction observed in evolocumab’s phase 3 trial in HeFH patients, RUTHERFORD-2 [18]. Specifically, the model draws on the unpublished treatment difference between evolocumab (administered once every two weeks) and placebo in average percentage change in calculated LDL-C levels from baseline to the mean of weeks 10 and 12 (61.31%; 95% CI: 57.82–64.80%).…”

Section: Methodsmentioning

confidence: 99%

“…The results of a trial in patients with HeFH showed that the addition of evolocumab to SoC (i.e. high-intensity statin therapy) led to a reduction in LDL-C levels of about 60% (RUTHERFORD-2 [18]).…”

Section: Introductionmentioning

confidence: 99%

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Cost-effectiveness of evolocumab in treatment of heterozygous familial hypercholesterolaemia in Bulgaria: measuring health benefit by effectively treated patient-years*

Borissov¹,

Urbich

Georgieva³

et al. 2017

Journal of Market Access & Health Policy

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Background: An elevated level of low-density lipoprotein cholesterol (LDL-C) constitutes one of the most important modifiable risk factors for cardiovascular disease (CVD). Individuals with heterozygous familial hypercholesterolaemia (HeFH) are particularly vulnerable to CVD events. The addition of evolocumab to statins has shown marked reductions in LDL-C levels. The objective of this analysis is to demonstrate the clinical and economic value of LDL-C lowering with evolocumab from the Bulgarian public health care perspective. Methods: A disease-specific measure of health benefit was devised: Effectively treated patient-years (ETPYs) combine length of life with the likelihood of attaining best-practice recommendations on LDL-C lowering. “Effective treatment” was defined as a reduction in LDL-C levels of ≥50%. A Markov cohort state-transition model was adapted, considering a life-long treatment duration. Demographics, baseline characteristics and efficacy data were taken from the RUTHERFORD-2 trial. The model uses the relationship between LDL-C lowering and reduced CVD event rates observed in the meta-analyses conducted by the Cholesterol Treatment Trialists’ Collaboration. Outcomes and costs (from year 2015) were discounted at an annual rate of 5%. Sensitivity analyses were conducted to assess uncertainty surrounding the results. Results: The total incremental costs of evolocumab added to statins versus statins alone are BGN 120,329 while adding 9.30 ETPYs over lifetime. These results imply an incremental cost per ETPY of BGN 12,937 (US$ 7,215; € 6,604). The use of evolocumab is associated with a relative reduction in the CVD event rate by 38% (18% per 1 mmol/L). Conclusions: Adding evolocumab to statins may be considered cost-effective in light of an additional expense per patient-year gained in which individuals with HeFH receive effective treatment under the terms of international prevention guidelines. ETPYs are an intuitive and clinically meaningful measure of patient benefit that, in relation to costs, can support health care decision-making that considers quality of care.

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Section: Methodsmentioning

confidence: 99%