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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

The efficacy and cost-effectiveness of evolocumab in the prevention of cardiovascular disease

Fahey, Kelly Marie 24 October 2018 (has links)
Heart disease is the leading cause of death in the United States. Hyperlipidemia is a predominant risk factor in the development of atherosclerotic cardiovascular disease (ASCVD). The statin drug class is the first line therapeutic for lowering atherogenic low-density lipoprotein (LDL) levels by competitively inhibiting 3-hydroxyl-3methyl-glutaryl-coenzyme A (HMGCR) reductase, the rate-limiting enzyme in cholesterol biosynthesis. However, there are patients who are unable to achieve desirable LDL levels despite statin therapy, such as those with familial hypercholesterolemia or those who are statin intolerant. A new therapy was discovered in 2015 to benefit patients with uncontrolled LDL levels by inhibiting Proprotein convertase subtilisin-kexin type 9 (PCSK9), a key protein in LDL receptor metabolism. Evolocumab (Repatha, AMGEN) is a human monoclonal antibody against human PSCK9. Evolocumab is approved to lower LDL-cholesterol in adult patients who have, despite dietary and lifestyle changes and maximally tolerated statin dose continued suboptimal lipid levels with either ASCVD or Heterozygous Familial Hypercholesterolemia (HeFH). Evolocumab has been shown to significantly reduce atherogenic lipid levels and the recent FOURNIER clinical trial showed that evolocumab reduces cardiovascular events. However, the high annual cost of evolocumab has raised questions as to its cost-effectiveness and role in the prevention and treatment of ASCVD. At the present price levels, this therapy does not appear to be cost-effective with multiple analyses suggesting significant price reduction will be necessary before this drug can be used in standard treatment for secondary prevention of cardiovascular disease in the United States.

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