scholarly journals Cost effectiveness of proprotein convertase subtilisin/ kexin type 9 (PCSK9) inhibitors

2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Abdulhalim Jamal Kinsara
Keyword(s):  
Cost Effectiveness ◽  
Proprotein Convertase ◽  
Pcsk9 Inhibitors

scholarly journals Neurocognitive effects associated with proprotein convertase subtilisin-kexin type 9 inhibitor use: a narrative review

2021 ◽  
Vol 12 ◽  
pp. 204209862095927
Author(s):  
Wei C. Yuet ◽  
Didi Ebert ◽  
Michael Jann
Keyword(s):  
Cognitive Impairment ◽  
Adverse Events ◽  
The United States ◽  
Narrative Review ◽  
Lipid Lowering ◽  
Patient Specific ◽  
Proprotein Convertase ◽  
Pcsk9 Inhibitors ◽  
Pcsk9 Inhibitor ◽  
Receptor Modulation

Neurocognitive adverse events have been observed with the widespread use of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors or “statins,” which reduce low-density lipoprotein cholesterol (LDL-C) levels and subsequently cardiovascular risk. The United States Food and Drug Association directed manufacturers of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors to monitor for neurocognitive adverse events due to their potent effects on LDL-C reduction, which is a proposed mechanism for neuronal cell dysfunction. Other proposed mechanisms for PCSK9 inhibitor-associated neurocognitive adverse events include N-methyl-d-aspartate receptor modulation, dysregulation of lipid and glucose metabolism, and patient-specific risk factors for cognitive impairment. The purpose of this narrative review article is to describe the proposed mechanisms, incidence of neurocognitive adverse events from phase II and III trials for PCSK9 inhibitors, neurocognitive assessments utilized in clinical trials, and clinical implications. Given the increasing prevalence of PCSK9 inhibitor use and the neurocognitive adverse events observed with prior lipid-lowering therapies, clinicians should be aware of the risks associated with PCSK9 inhibitors, especially when therapy is indicated for patients at high risk for cardiovascular events. Overall, the incidence of PCSK9 inhibitor-associated neurocognitive appears to be uncommon. However, additional prospective studies evaluating cognitive impairment may be beneficial to determine the long-term safety of these agents.

scholarly journals The history of proprotein convertase subtilisin kexin-9 inhibitors and their role in the treatment of cardiovascular disease

2020 ◽  
Vol 11 ◽  
pp. 204062232092456
Author(s):  
Eun Ji Kim ◽  
Anthony S. Wierzbicki
Keyword(s):  
Cardiovascular Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Epidemiological Studies ◽  
Lipid Lowering ◽  
Proprotein Convertase ◽  
Pcsk9 Inhibitors ◽  
Activating Mutations ◽  
History Of ◽  
New Guidelines

A consensus has formed based on epidemiological studies and clinical trials that intervention to reduce low density lipoprotein cholesterol (LDL-C) will reduce cardiovascular disease (CVD) events. This has progressively reduced the thresholds for intervention and targets for treatment. Whist statins are sufficient for many people in primary prevention, they only partially achieve the newer targets of secondary prevention for established CVD. Increasing use of statins has highlighted that 1–2% cannot tolerate these drugs. Other cholesterol-lowering drugs such as ezetimibe add to the benefits of statins but have limited efficacy. The discovery of activating mutations in proprotein convertase subtilisin kexin-9 (PCSK9) as a cause of familial hypercholesterolaemia while inactivating mutations lower LDL-C led to the idea to develop PCSK9 inhibitors as drugs. This article reviews the history of lipid-lowering therapies, the discovery of PCSK9 and the development of PCSK9 inhibitors. It reviews the key trials of the current antibody-based drugs and how these have influenced new guidelines. It also reviews the controversy caused by their cost and the increasing application of health economics to determine the optimum strategy for implementation of novel therapeutic pathways and surveys other options for targeting PCSK9 as well as other LDL-C lowering compounds in late development.

2981Treatment of Hypercholesterolaemia with PCSK9 Inhibitors in Denmark. Assessment of real-life data; Extent and Efficacy after the first years of clinical use

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Mulverstedt ◽  
I C Klausen ◽  
H Kanstrup ◽  
J Knold ◽  
L J Andersen ◽  
...  
Keyword(s):  
Familial Hypercholesterolaemia ◽  
Plasma Lipids ◽  
Coronary Revascularization ◽  
Real Life ◽  
Atherosclerotic Cardiovascular Disease ◽  
Proprotein Convertase ◽  
Pcsk9 Inhibitors ◽  
Statin Intolerance ◽  
Treatment Target ◽  
Number Of Patients

Abstract Introduction Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9 I) are a new group of drugs for treatment of hypercholesterolaemia. At present there are two available drugs evolocumab and alirocumab, which lowers low-density lipoprotein cholesterol (LDL-C) by inhibiting the enzyme proprotein convertase subtilisin/kexin type 9. Both evolocumab and alirocumab outcome data (FOURIER and ODYSSEY OUTCOMES respectively) have shown a reduced risk of myocardial infarction, stroke, and coronary revascularization without adverse effects. Patients included in these trials had existing atherosclerotic cardiovascular disease and all patients received maximum-tolerated statin. In the FOURIER trail 100% of the patients received statin and 69% high intensity statin, in the ODYSSEY trial is was 98% and 89%, respectively Purpose In collaboration with lipid clinics in Denmark we aimed to describe the clinical characteristics of patients treated, along with the efficacy of LDL-C reduction of such treatment in a real-life population. Methods We contacted lipid and cardiological clinics throughout Denmark and obtained clinical data on the majority of patients treated with PCSK9 I in Denmark between October 1st, 2015 and May 1st, 2018. A database containing information on medical history, medications used prior to PCSK9 I initiation, adverse events and plasma lipids including LDL-C was created. Records of baseline LDL-C and at follow up visits were analysed. Results From October 1st 2015 to may 1st2018, 383 patients were enrolled; an estimated 90% of all patients in Denmark. The distribution of clinical indications for PCSK9 I initiation is shown in figure 1. A total 243 of these patients (63.4%) were characterised as statin intolerant and 225 (58.7%) had familial hypercholesterolaemia. More than two thirds (69.5%) of the patients were given PCSK9 Inhibitors as secondary prophylaxis. Overall LDL was significantly reduced from 5.11 mmol/L (CI [4.95; 5.28]) to 2.46 mmol/L (CI [2.33–2.68]) after the first month of treatment, corresponding to a 48.9% decrease in LDL-C, which persisted without significant changes throughout the two years of observation. Even with this reduction, only about half of the population of both primary and secondary prevention reached their treatment target. This remained unchanged in patients with familial hypercholesterolaemia an those with statin intolerance (Table 1). A subgroup analysis showed a significantly lower LDL in the first 12 months when PCSK9 I were combined with statins versus PCSK9 I as monotherapy (p<0.05) (results not shown). Conclusion Patients treated with PCSK9 I in this real-life do not resemble the populations in the major endpoint studies, as the majority in this real-life population are statin intolerant. Nevertheless, we see an overall reduction of LDL of approx. 50%, even though the number of patients reaching their treatment target remains low (approx. 50% at best).

Recent advances in the understanding and care of familial hypercholesterolaemia: significance of the biology and therapeutic regulation of proprotein convertase subtilisin/kexin type 9

2015 ◽  
Vol 129 (1) ◽  
pp. 63-79 ◽  
Author(s):  
Michael M. Page ◽  
Claudia Stefanutti ◽  
Allan Sniderman ◽  
Gerald F. Watts
Keyword(s):  
Genetic Testing ◽  
Familial Hypercholesterolaemia ◽  
Lipoprotein Metabolism ◽  
New Drugs ◽  
High Density Lipoproteins ◽  
Proprotein Convertase ◽  
Pcsk9 Inhibitors ◽  
Statin Intolerance ◽  
Cascade Screening ◽  
Recent Advances

Familial hypercholesterolaemia (FH) is an autosomal co-dominant disorder that markedly raises plasma low-density lipoprotein-cholesterol (LDL-C) concentration, causing premature atherosclerotic coronary artery disease (CAD). FH has recently come under intense focus and, although there is general consensus in recent international guidelines regarding diagnosis and treatment, there is debate about the value of genetic studies. Genetic testing can be cost-effective as part of cascade screening in dedicated centres, but the full mutation spectrum responsible for FH has not been established in many populations, and its use in primary care is not at present logistically feasible. Whether using genetic testing or not, cholesterol screening of family members of index patients with an abnormally raised LDL-C must be used to determine the need for early treatment to prevent the development of CAD. The metabolic defects in FH extend beyond LDL, and may affect triacylglycerol-rich and high-density lipoproteins, lipoprotein(a) and oxidative stress. Achievement of the recommended targets for LDL-C with current treatments is difficult, but this may be resolved by new drug therapies. Lipoprotein apheresis remains an effective treatment for severe FH and, although expensive, it costs less than the two recently introduced orphan drugs (lomitapide and mipomersen) for homozygous FH. Recent advances in understanding of the biology of proprotein convertase subtilisin/kexin type 9 (PCSK9) have further elucidated the regulation of lipoprotein metabolism and led to new drugs for effectively treating hypercholesterolaemia in FH and related conditions, as well as for treating many patients with statin intolerance. The mechanisms of action of PCSK9 inhibitors on lipoprotein metabolism and atherosclerosis, as well as their impact on cardiovascular outcomes and cost-effectiveness, remain to be established.

scholarly journals Updated Cost-effectiveness Assessments of PCSK9 Inhibitors From the Perspectives of the Health System and Private Payers

2017 ◽  
Vol 2 (12) ◽  
pp. 1369 ◽  
Author(s):  
Alejandro Arrieta ◽  
Jonathan C. Hong ◽  
Rohan Khera ◽  
Salim S. Virani ◽  
Harlan M. Krumholz ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Health System ◽  
Pcsk9 Inhibitors
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