Evolocumab

OBJECTIVE: To evaluate the efficacy, safety, and cost-effectiveness of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors and describe its place in therapy for the treatment of hypercholesterolemia. DATA SOURCES: A search of MEDLINE, CINAHL, and Clinicaltrials.gov was performed from January 2012 to March 2018 to identify literature pertaining to PCSK9 inhibitors using pre-specified search terms. Additional references were identified from citations of the literature...

OBJECTIVE: To summarize 10 high-quality studies from 2017 that have strong relevance to primary care practice. QUALITY OF EVIDENCE: Study selection involved routine literature surveillance by a group of primary care health professionals. This included screening abstracts of important journals and Evidence Alerts, as well as searching the American College of Physicians Journal Club. MAIN MESSAGE: Topics of the 2017 articles include whether treating subclinical hypothyroidism improves outcomes or symptoms; whether evolocumab reduces cardiovascular disease as well as low-density lipoprotein levels; whether lifestyle interventions reduce medication use in patients with diabetes; whether vitamin D prevents cardiovascular disease, cancer, or upper respiratory tract infections; whether canagliflozin reduces clinical events in patients with diabetes; how corticosteroid injections affect knee osteoarthritis; whether drained abscesses benefit from antibiotic treatment; whether patients with diabetes benefit from bariatric surgery; whether exenatide reduces clinical events in patients with diabetes; and whether tympanostomy tubes affect outcomes in recurrent acute otitis media or chronic otitis media...

We report the case of a patient with probable heterozygous familial hypercholesterolemia and mitotane-induced resistant hypercholesterolemia, despite combination therapy with rosuvastatin and ezetimibe. The patient was managed with the addition of evolocumab. Use of a proprotein convertase subtilisin-kexin type 9 inhibitor, should be considered in patients who develop mitotane-related hypercholesterolemia that cannot be managed with conventional lipid-lowering treatment.

Background -The FOURIER trial recently showed that the PCSK9 inhibitor evolocumab significantly reduced major vascular events in patients with stable atherosclerotic cardiovascular disease, including patients with prior MI. Within the broad group of patients with prior MI, we hypothesized that readily ascertainable features would identify subsets that derive greater clinical risk reduction with evolocumab. Methods -The 22,351 patients with a prior MI were characterized based on time from most recent MI, number of prior MIs, and presence of residual multivessel coronary artery disease (≥40% stenosis in ≥2 large vessels)...

BACKGROUND: Evolocumab, a proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor, has been shown to reduce low-density lipoprotein levels by up to 60%. Despite the absence of a reduction in overall or cardiovascular mortality in the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) trial, some believe that, with longer treatment, such a benefit might eventually be realized. Our aim was to estimate the potential mortality benefit over a patient's lifetime and the cost per year of life saved (YOLS) for an average Canadian with established coronary artery disease...

Aims: Lipoprotein(a) [Lp(a)], a low-density lipoprotein (LDL) particle covalently bound to apolipoprotein(a) [apo(a)], is a potentially potent heritable risk factor for cardiovascular disease. We investigated the mechanism whereby evolocumab, a monoclonal antibody against proprotein convertase subtilisin-kexin type 9 (PCSK9), lowers Lp(a). Methods and results: We studied the kinetics of Lp(a) particles in 63 healthy men, with plasma apo(a) concentration >5 nmol/L, participating in an 8-week factorial trial of the effects of evolocumab (420 mg every 2 weeks) and atorvastatin (80 mg daily) on lipoprotein metabolism...

PURPOSE OF REVIEW: A number of novel trials have assessed the efficacy of new lipid-lowering therapies in cardiovascular disease (CVD). RECENT FINDINGS: Proprotein convertase subtilisin kexin-9 inhibitors reduce low-density lipoprotein cholesterol (LDL-C) by 50-55%. A CVD outcome trial in patients with acute coronary syndromes with evolocumab achieved a LDL-C of 0.8 mmol/l (31 mg/dl) and a 20% relative risk reduction in CVD events in 2.2 years. Cholesterol ester transfer protein inhibitors raise high-density lipoprotein cholesterol and can lower LDL-C...

BACKGROUND: The reduction of cholesterol levels with cholesterol-lowering therapy may improve endothelial function. Lipid-lowering therapy has been greatly enhanced by the introduction of proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies. Less is known of the effect of PCSK9 inhibitors on endothelial function of subjects with hypercholesterolemia. OBJECTIVE: To assess whether treatment with PCSK9 inhibitors may improve endothelial function evaluated by brachial artery vasoreactivity test...

BACKGROUND : In the FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Patients With Elevated Risk), the PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor evolocumab reduced low-density lipoprotein cholesterol (LDL-C) and cardiovascular risk. It is not known whether the efficacy of evolocumab is modified by baseline inflammatory risk. We explored the efficacy of evolocumab stratified by baseline high-sensitivity C-reactive protein (hsCRP). We also assessed the importance of inflammatory and residual cholesterol risk across the range of on-treatment LDL-C concentrations...

PURPOSE OF REVIEW: To review the efficacy, safety, pharmacology, and pharmacokinetics of evolocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor. RECENT FINDINGS: PCSK9 inhibitors are a class of lipid-lowering agents that significantly reduce low-density lipoprotein cholesterol (LDL-C) levels in patients with atherosclerotic cardiovascular disease and hyperlipidemia. Evolocumab is a monoclonal antibody that inhibits PCSK9 and has been evaluated in phase II and III studies as monotherapy, in combination with statins and other lipid-lowering therapies, in patients who are statin intolerant, and in patients with heterozygous and homozygous familial hypercholesterolemia...

PCSK9-inhibitors belong to the new class of hypolipidemic agents. They enhance catabolism of low density lipoprotein cholesterol (LDL-C) through inhibiting activity of proprotein convertase subtilisin/kexin type 9 (PCSK9). They are monoclonal antibodies (alirocumab, evolocumab etc). Under clinical development are also other types of PCSK9-inhibitors which act at a subcellular level. The treatment with PCSK9-inhibitors can be beneficially combined with lipoprotein apheresis (LA). If such treatment using PCSK9-inhibitors is possible with regard to an individual patients genotype, the combination of LA and PCSK9-inhibitors leads to slowing the space of LDL-C increase between individual procedures of apheresis and enables attaining of the lowest possible values of LDL-cholesterolemia for the longest possible period of time...

PCSK9 (proprotein convertase subtilisin kexin 9) monoclonal antibodies (mAb) are new therapeutic agents to lower efficiently LDL-cholesterol levels. New data from large clinical trials suggest that the addition of PCSK9 mAb to statins can reduce the incidence of major adverse cardiovascular events in very high risk patients. Alirocumab and evolocumab are two agents available in Switzerland with specific limitations for reimbursement. PCSK9 mAb should be considered in patients with clinical atherosclerotic cardiovascular disease (ASCVD), as well as in patients with familial hypercholesterolemia without ASCVD who have substantially high LDL-cholesterol levels despite the use of statin at maximally tolerated dose with or without ezetimibe, or intolerance to appropriate doses of several statins...

Elevated low-density lipoprotein cholesterol (LDL-C) plays a major role in the development of atherosclerotic cardiovascular disease. Statins are the first-line treatment to lower LDL-C in patients with hypercholesterolemia; however, some high cardiovascular risk patients may have inadequate responses to statin therapy or are intolerant to statins, and may need additional and/or alternative non-statin therapies to further reduce their LDL-C levels. Monoclonal antibodies that inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of circulating LDL-C levels, have received considerable attention as promising non-statin therapeutic options for the management of hypercholesterolemia...

Despite recent therapeutic advances, there is an unmet need in cardiovascular disease prevention. Clinical trials and meta-analyses have established that LDL-C lowering, particularly by statin therapy, reduces the progression of coronary atherosclerosis and the risk of coronary events. Insufficient LDL-C reduction and high residual risk in a significant proportion of statin-treated patients signify that additional therapies are required to deliver more effective coronary care. Pharmacological inhibition of cholesterol absorption (with ezetimibe) and PCSK9 activity (with evolocumab or alirocumab) provides potentially useful approaches for the therapeutic modulation of LDL-C metabolism in statin-treated patients...

Lipoprotein apheresis and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are last therapeutic resorts in patients with familial hypercholesterolemia (FH). We explored changes in lipoprotein subclasses and high-density lipoprotein (HDL) function when changing treatment from lipoprotein apheresis to PCSK9 inhibition. We measured the levels of low-density lipoprotein (LDL) and HDL particle subclasses, serum amyloid A1 (SAA1), paraoxonase-1 (PON1) activity and cholesterol efflux capacity (CEC) in three heterozygous FH patients...

AIMS: To investigate the effect of two clinically applied proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9-mAbs) on glycaemia and new-onset diabetes mellitus (NODM). MATERIALS AND METHODS: PubMed, MEDLINE, Embase, Cochrane databases and ClinicalTrials.gov websites were systematically searched for randomized controlled trials that reported data on fasting plasma glucose (FPG), glycated haemoglobin (HbA1c) or NODM incidence. Risk ratios (RRs) for NODM and mean difference (MD) for FPG and HbA1c with 95% confidence intervals (CIs) were calculated using a fixed-effect model...

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Prevention and treatment of dyslipidemia should be considered as an integral part of individual cardiovascular prevention interventions, which should be addressed primarily to those at higher risk who benefit most. To date, statins remain the first-choice therapy, as they have been shown to reduce the risk of major vascular events by lowering low-density lipoprotein cholesterol (LDL-C). However, due to adherence to statin therapy or statin resistance, many patients do not reach LDL-C target levels. Ezetimibe, fibrates, and nicotinic acid represent the second-choice drugs to be used in combination with statins if lipid targets cannot be reached...