Long-Term Evolocumab in Patients With Familial Hypercholesterolemia

Santos, Raúl D.; Stein, Evan A.; Hovingh, G. Kees; Blom, Dirk; Soran, Handrean; Watts, Gerald F.; López, J. Antonio G.; Bray, Sarah; Kurtz, Christopher; Hamer, Andrew; Raal, Frederick J.

doi:10.1016/j.jacc.2019.12.020

Cited by 149 publications

(121 citation statements)

References 28 publications

Supporting

Mentioning

112

Contrasting

Unclassified

Order By: Relevance

“…In the TAUSSIG trial, responses were similarly variable and an analysis by mutation type revealed consistently poor responses in HoFH patients with null LDLR mutations [23]. Long-term data from TAUSSIG suggests a mean response rate of evolocumab in FH of 21.2% [24]. The issues with variability of response to PCSK9 inhibitors in HoFH indicate a need to carefully select therapies based on available genetic profiling [25].…”

Section: Standards Of Carementioning

confidence: 99%

Lomitapide–a Microsomal Triglyceride Transfer Protein Inhibitor for Homozygous Familial Hypercholesterolemia

Stefanutti

2020

Curr Atheroscler Rep

View full text Add to dashboard Cite

Purpose of Review Homozygous familial hypercholesterolemia (HoFH) is a rare, genetic condition characterized by high levels of Low density lipoprotein cholesterol (LDL-C); overt, early-onset atherosclerotic cardiovascular disease (ASCVD); and premature cardiovascular events and mortality. Lomitapide is a first-in-class microsomal triglyceride transfer protein inhibitor for the treatment of HoFH. This review provides an update on data emerging from real-world studies of lomitapide following on from its pivotal phase 3 clinical trial in HoFH. Recent Findings Recent registry data have confirmed that HoFH is characterized by delayed diagnosis, with many patients not receiving effective therapy until they are approaching the age when major adverse cardiovascular events may occur. Data from case series of varying sizes, and from a 163-patient registry of HoFH patients receiving lomitapide, have demonstrated that lomitapide doses are lower and adverse events less severe than in the phase 3 study. Lomitapide enables many patients to reach European Atherosclerosis Society LDL-C targets. Some patients are able to reduce frequency of lipoprotein apheresis or, in some cases, stop the procedure altogether-unless there is significant elevation of lipoprotein (a). Modelling analyses based on historical and clinical trial data indicate that lomitapide has the potential to improve cardiovascular outcomes and survival in HoFH. Summary Real-world clinical experience with lomitapide has shown the drug to be effective with manageable, less marked adverse events than in formal clinical studies. Event modelling data suggest a survival benefit with lomitapide in HoFH.

show abstract

Section: Standards Of Carementioning

confidence: 99%

Lomitapide–a Microsomal Triglyceride Transfer Protein Inhibitor for Homozygous Familial Hypercholesterolemia

Stefanutti

2020

Curr Atheroscler Rep

View full text Add to dashboard Cite

show abstract

“…In a meta-study, it was found that when evolucomab is given as a 420 mg monthly dose, LDL-C could be reduced by 54.71%, indicating that evolocumab might be a potential drug for FH patients ( Eslami et al, 2017 ). It has also been found that alirocumab treatment is well-tolerated in heterozygous FH (HeFH) patients and could significantly reduce LDL-C by 12 and 24 weeks while evolocumab could effectively reduce the LDL-C levels in HoFH or severe HeFH patients over a median of 4.1 years ( Ginsberg et al, 2019 ; Santos et al, 2020 ). In summary, PCSK9 inhibitors can significantly reduce LDL-C, even in FH patients who have not yet achieved their LDL-C goals.…”

Section: From Diagnosis Methods To Therapy Strategies Of Fh Based On mentioning

confidence: 99%

PCSK9 Variants in Familial Hypercholesterolemia: A Comprehensive Synopsis

2020

View full text Add to dashboard Cite

Autosomal dominant familial hypercholesterolemia (FH) affects approximately 1/250, individuals and potentially leads to elevated blood cholesterol and a significantly increased risk of atherosclerosis. Along with improvements in detection and the increased early diagnosis and treatment, the serious burden of FH on families and society has become increasingly apparent. Since FH is strongly associated with proprotein convertase subtilisin/kexin type 9 ( PCSK9 ), increasing numbers of studies have focused on finding effective diagnostic and therapeutic methods based on PCSK9 . At present, as PCSK9 is one of the main pathogenic FH genes, its contribution to FH deserves more explorative research.

show abstract

“…The reported LDL-C reduction with PCSK9i reaches 57% in different populations including homozygous or heterozygous FH [25] . Two trials providing cardiovascular outcome data are now published.…”

Section: Management Optionsmentioning

confidence: 96%

“…The primary endpoint was the incidence of adverse and the secondary endpoints were changes in LDL-C and other lipids. A total of 300 patients were evaluated and evolocumab was well tolerated and effectively reduced plasma LDL-C levels in patients with homozygous and heterozygous FH during the follow up period of 4.1 years [25] .…”

Section: Management Optionsmentioning

confidence: 99%

Improvement initiative in LDL-C management in Saudi Arabia: A call to action

Alasnag

Awan

Ghamdi

et al. 2020

IJC Heart & Vasculature

View full text Add to dashboard Cite

Purpose Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death in the Saudi Arabia (KSA). Over the last decade dyslipidemia has been the predominant risk factor in KSA. The linear relationship between low density lipoprotein cholesterol (LDL-C) levels, a marker for dyslipidemia, and progression of ASCVD is well established. The objective of this paper is to to provide an overview of the burden of disease, outline current clinical practice guidelines (CPG), examine gaps in care, and provide actionable recommendations to prevent, diagnose, and treat dyslipidemia in KSA. Results Saudi Arabia has the highest prevalence of ASCVD in the Gulf region. Several gaps in the implementation of CPGs, including the underdiagnosis and undertreatment of dyslipidemia, inadequate primary and secondary prevention efforts, complicated by a fragmented health system have been identified. Compelling evidence indicates that target LDL-C levels are not achieved throughout the Middle East region. In addition, high-risk patients are often left unidentified with adequate treatment. Conclusion This statement recommends specific multilevel interventions to optimize the prevention, diagnosis, and treatment of ASCVD. These recommendations focus on strengthening primary and secondary prevention through education initiatives, establishment of specialized prevention and treatment centers, and development of local and regional CPGs.

show abstract

Long-Term Evolocumab in Patients With Familial Hypercholesterolemia

Cited by 149 publications

References 28 publications

Lomitapide–a Microsomal Triglyceride Transfer Protein Inhibitor for Homozygous Familial Hypercholesterolemia

Lomitapide–a Microsomal Triglyceride Transfer Protein Inhibitor for Homozygous Familial Hypercholesterolemia

PCSK9 Variants in Familial Hypercholesterolemia: A Comprehensive Synopsis

Improvement initiative in LDL-C management in Saudi Arabia: A call to action

Contact Info

Product

Resources

About