Long-Term Efficacy and Safety of Evolocumab in Patients With Hypercholesterolemia

Koren, Michael; Sabatine, Marc S.; Giugliano, Robert P.; Langslet, Gisle; Wiviott, Stephen D.; Ruzza, Andrea; Ma, Yuhui; Hamer, Andrew; Wasserman, Scott M.; Raal, Frederick J.

doi:10.1016/j.jacc.2019.08.1024

Cited by 115 publications

(86 citation statements)

References 21 publications

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“…Several studies evaluated a PCSK9 inhibitor in varying cardiovascular risk patients, who failed to achieve target LDL-C levels with primary lipid-lowering strategies (LDL-C less than 70 mg/dL). In two open-label studies (OSLER (Open-Label Study of Long Term Evaluation Against LDL-C Trial) 1 and 2, 2019), evolocumab reduced LDL-C targets by 61% more than the standard care at 12 weeks [17][18]. In patients with high cardiovascular risk, the LAPLACE-2 (LDL-C Assessment with PCSK9 Monoclonal Antibody Inhibition Combined With Statin Therapy) study demonstrated that evolocumab, when added to atorvastatin, resulted in high rates of LDL-C targets at 12 weeks [19].…”

Section: Resultsmentioning

confidence: 99%

Modern Lipid Management: A Literature Review

Malik

Shabeer

Ishaq

et al. 2020

Cureus

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Section: Resultsmentioning

confidence: 99%

Modern Lipid Management: A Literature Review

Malik

Shabeer

Ishaq

et al. 2020

Cureus

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“…As well, around 5% of patients who received alirocumab developed anti-drug antibodies -a percentage that was furthermore reduced to 1.3%-, but without alteration in the LDL-C reduction rate [86]. According to the OSLER-1 long term trial, transient ADAs rarely occurred in patients taking evolocumab, and none was detected after the first-year treatment [63]. There were not significant neurocognitive disorders caused by evolocumab (EBBINGHAUS [70], REGARDS [87]), Table 1.…”

Section: Adverse Eventsmentioning

confidence: 98%

“…It has two elimination phases, while it has an estimated half-life is 11-17 days [60]. A negligible amount of anti-drug antibodies has been reported for evolocumab treated patients [63].…”

Section: Monoclonal Antibodies For Cholesterol-loweringmentioning

confidence: 99%

Progress and prospects of biological approaches targeting PCSK9 for cholesterol-lowering, from molecular mechanism to clinical efficacy

Malvandi

Canclini

Alliaj

et al. 2020

Expert Opinion on Biological Therapy

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Introduction: Cardiovascular disorders are one of the leading causes of mortality and morbidity worldwide. Recent advances showed a promising role of proprotein convertase subtilisin/kexin type 9 (PCSK9) as a critical player in regulating plasma LDL levels and lipid metabolism. Areas covered: This review addresses the molecular functions of PCSK9 with a vision on the clinical progress of utilizing monoclonal antibodies and other biological approaches to block PCSK9 activity. The successful clinical trials with monoclonal antibodies are reviewed. Recent advances in (pre)clinical trials of other biological approaches, such as small interfering RNAs, are also discussed. Expert opinion: Discovery of PCSK9 and clinical use of its inhibitors to manage lipid metabolism is a step forward in hypolipidaemic therapy. A better understanding of the molecular activity of PCSK9 can help to identify new approaches in the inhibition of PCSK9 expression/activity. Whether if PCSK9 plays a role in other cardiometabolic conditions may provide grounds for further development of therapies.

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“…From the safety perspective, absence of worrisome adverse reactions in short-term clinical trials does not rule out all possible safety issues. More data on the longterm effects associated with very low LDL-C levels over many years are needed, although neither genetic studies [4] nor evidence with evolocumab at 5 years [43] and ezetimibe at 6 years have shown harm [22]. In this context, post-market surveillance data and registries could provide additional relevant long-term safety data.…”

Section: Final Considerations and Future Perspectivesmentioning

confidence: 99%

What Lessons Have We Learned and What Remains to be Clarified for PCSK9 Inhibitors? A Review of FOURIER and ODYSSEY Outcomes Trials

Furtado

Giugliano

2020

Cardiol Ther

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For more than half a century, low-density lipoprotein cholesterol (LDL-C) has been recognized as a major risk factor for incident atherosclerotic cardiovascular disease. The discovery of proprotein convertase subtilisin-kexin type 9 (PCSK9) in 2003, which prevents LDL-C receptor recycling, identified a new target for drug intervention. Recently, two large-scale randomized clinical outcomes trials involving fully human anti-PCSK9 monoclonal antibodies tested the hypothesis that targeting this pathway would reduce cardiovascular events. Both the FOURIER (Further cardiovascular OUtcomes Research with PCSK9 Inhibition in subjects with Elevated Risk) and ODYSSEY OUTCOMES trials met their primary efficacy endpoints, confirming findings reported earlier that major adverse cardiovascular events can be reduced by a further lowering of LDL-C beyond that achieved with statin therapy. In both trials, there were incremental reductions in LDL-C of[50% from baseline, with no major safety concerns, over the trials' median follow-up time (2.2 and 2.8 years, respectively). While there were differences in design, lipid management and overall results, key messages from both studies were similar. However, post-publication, additional questions have arisen, especially regarding drug effects over the long-term, including a potential mortality benefit.

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Long-Term Efficacy and Safety of Evolocumab in Patients With Hypercholesterolemia

Cited by 115 publications

References 21 publications

Modern Lipid Management: A Literature Review

Modern Lipid Management: A Literature Review

Progress and prospects of biological approaches targeting PCSK9 for cholesterol-lowering, from molecular mechanism to clinical efficacy

What Lessons Have We Learned and What Remains to be Clarified for PCSK9 Inhibitors? A Review of FOURIER and ODYSSEY Outcomes Trials

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