keyword
MENU ▼
Read by QxMD icon Read
search

Alirocumab

keyword
https://www.readbyqxmd.com/read/29792380/alirocumab-as-add-on-therapy-to-statins-current-evidence-and-clinical-potential
#1
Johann Auer, Robert Berent
Atherosclerotic cardiovascular diseases (ASCVDs) are associated with a substantial mortality, physical morbidity, and mental disability. Elevated plasma low-density lipoprotein cholesterol (LDL-C) levels play a major role in the pathophysiology of ASCVDs. Statins have been shown to reduce ASCVD risk and associated events and are recommended as first-line therapy for treatment of hypercholesterolemia by current international guidelines. The key issue is to attain guideline-recommended LDL-C levels (below 70 mg/dl) for patients at very high cardiovascular risk...
May 1, 2018: Therapeutic Advances in Cardiovascular Disease
https://www.readbyqxmd.com/read/29779195/efficacy-and-safety-of-alirocumab-in-individuals-with-diabetes-mellitus-pooled-analyses-from-five-placebo-controlled-phase-3-studies
#2
Henry N Ginsberg, Michel Farnier, Jennifer G Robinson, Christopher P Cannon, Naveed Sattar, Marie T Baccara-Dinet, Alexia Letierce, Maja Bujas-Bobanovic, Michael J Louie, Helen M Colhoun
INTRODUCTION: Diabetes mellitus (DM) carries an elevated risk for cardiovascular disease. Here, we assessed alirocumab efficacy and safety in people with/without DM from five placebo-controlled phase 3 studies. METHODS: Data from up to 78 weeks were analyzed in individuals on maximally tolerated background statin. In three studies, alirocumab 75 mg every 2 weeks (Q2W) was increased to 150 mg Q2W at week 12 if week 8 low-density lipoprotein cholesterol (LDL-C) was ≥ 70 mg/dL; two studies used alirocumab 150 mg Q2W throughout...
May 19, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29753563/critical-appraisal-of-the-2018-acc-scientific-sessions-late-breaking-trials-from-a-statistician-s-perspective
#3
REVIEW
Stuart J Pocock, Tim J Collier
The late-breaking clinical trials presentations at the American College of Cardiology Scientific Sessions in March 2018 are an important contribution to the field of cardiology. This paper presents a constructive critical appraisal of 7 key studies: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), VEST (Vest Prevention of Early Sudden Death Trial), SECURE-PCI (Statins Evaluation in Coronary Procedures and Revascularization), TREAT (Ticagrelor in Patients with ST-Elevation Myocardial Infarction treated with Pharmacological Thrombolysis), POISE (PeriOperative ISchemic Evaluation), SMART-DATE (Safety of 6-Month Duration of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention in Patients With Acute Coronary Syndrome), and CVD-REAL 2 (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors)...
May 7, 2018: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29725997/population-pharmacokinetic-pharmacodynamic-analysis-of-alirocumab-in-healthy-volunteers-or-hypercholesterolemic-subjects-using-an-indirect-response-model-to-predict-low-density-lipoprotein-cholesterol-lowering-support-for-a-biologics-license-application-submission
#4
Xavier Nicolas, Nassim Djebli, Clémence Rauch, Aurélie Brunet, Fabrice Hurbin, Jean-Marie Martinez, David Fabre
BACKGROUND: Alirocumab, a human monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly lowers low-density lipoprotein cholesterol levels. OBJECTIVE: This analysis aimed to develop and qualify a population pharmacokinetic/pharmacodynamic model for alirocumab based on pooled data obtained from 13 phase I/II/III clinical trials. METHODS: From a dataset of 2799 individuals (14,346 low-density lipoprotein-cholesterol values), individual pharmacokinetic parameters from the population pharmacokinetic model presented in Part I of this series were used to estimate alirocumab concentrations...
May 3, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29725996/population-pharmacokinetic-analysis-of-alirocumab-in-healthy-volunteers-or-hypercholesterolemic-subjects-using-a-michaelis-menten-approximation-of-a-target-mediated-drug-disposition-model-support-for-a-biologics-license-application-submission-part-i
#5
Jean-Marie Martinez, Aurélie Brunet, Fabrice Hurbin, A Thomas DiCioccio, Clémence Rauch, David Fabre
BACKGROUND: Alirocumab, a human monoclonal antibody, inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9) to significantly reduce low-density lipoprotein cholesterol levels; pharmacokinetics (PK) are governed by non-linear, target-mediated drug disposition (TMDD). OBJECTIVES: We aimed to develop and qualify a population PK (PopPK) model to characterize the PK profile of alirocumab, evaluate the impact of covariates on alirocumab PK and on individual patient exposures, and estimate individual predicted concentrations for a subsequent PK/pharmacodynamic (PD) analysis...
May 3, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29724769/pcsk9-inhibition-with-alirocumab-reduces-lipoprotein-a-levels-in-non-human-primates-by-lowering-apolipoprotein-a-production-rate
#6
Mikaël Croyal, Thi-Tu-Trang Tran, Rose Hélène Blanchard, Jean-Christophe Lebail, Elise F Villard, Bruno Poirier, Audrey Aguesse, Stéphanie Billon-Crossouard, Stéphane Ramin-Mangata, Valentin Blanchard, Brice Nativel, Kévin Chemello, Ilya Khantalin, Aurélie Thedrez, Philip Janiak, Michel Krempf, Christophe Boixel, Gilles Lambert, Etienne Guillot
Therapeutic antibodies targeting PCSK9 (e.g. alirocumab) lower low-density lipoprotein cholesterol (LDL-C) and lipoprotein (a) [Lp(a)] levels in clinical trials. We recently showed that PCSK9 enhances apolipoprotein(a) [apo(a)] secretion from primary human hepatocytes but does not affect Lp(a) cellular uptake. Here we aimed to determine how PCSK9 neutralization modulates Lp(a) levels in vivo. Six non-human primates (NHP) were treated with alirocumab or a control antibody (IgG1) in a crossover protocol. After the lowering of lipids reached steady state, NHP received an intravenous injection of [2H3]-leucine, and blood samples were collected sequentially over 48 hours...
May 3, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29713852/correction-to-assessment-of-the-1-of-patients-with-consistent-15-reduction-in-low-density-lipoprotein-cholesterol-pooled-analysis-of-10-phase-3-odyssey-alirocumab-trials
#7
Harold E Bays, Robert S Rosenson, Marie T Baccara-Dinet, Michael J Louie, Desmond Thompson, G Kees Hovingh
The original version of this article unfortunately contained a mistake in the Discussion section.
April 27, 2018: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/29706812/usefulness-of-alirocumab-and-evolocumab-for-the-treatment-of-patients-with-diabetic-dyslipidemia
#8
REVIEW
Jun Zhang, Kristen M Tecson, Natalia A Rocha, Peter A McCullough
In 2015, the US Food and Drug Administration (FDA) approved the anti-proprotein convertase subtilsin/kexin type 9 (PCSK9) monoclonal antibodies, alirocumab and evolocumab, to treat patients with hypercholesterolemia and mixed dyslipidemia. Since then, considerable attention has been paid to the use of these monoclonal antibodies for the treatment of diabetic dyslipidemia with a goal of reducing the risk for cardiovascular disease. Recently, consensus statements on the clinical use of PCSK9 inhibitors in patients with type 2 diabetes mellitus, who are unable to achieve the goal of low-density lipoprotein cholesterol (<70 mg/dL or <1...
April 2018: Proceedings of the Baylor University Medical Center
https://www.readbyqxmd.com/read/29692249/pcsk9-inhibitors-novel-therapeutic-strategies-for-lowering-ldl-cholesterol
#9
Zhao-Peng Liu, Yan Wang
Statins are currently the major therapeutic strategies to lower low-density lipoprotein cholesterol (LDL-C) levels. However, a number of hypercholesterolemia patients still have a residual cardiovascular disease (CVD) risk despite taking the maximum-tolerated dose of statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to low-density lipoprotein receptor (LDLR), inducing its degradation in the lysosome and inhibiting LDLR recirculating to the cell membranes. The gain-of-function mutations in PCSK9 elevate the LDL-C levels in plasma...
April 22, 2018: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/29667842/the-role-of-pcsk9-inhibitors-in-the-treatment-of-hypercholesterolemia
#10
Roshni S Patel, Emily M Scopelliti, Oludamilola Olugbile
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...
April 1, 2018: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/29627892/assessment-of-the-1-of-patients-with-consistent-15-reduction-in-low-density-lipoprotein-cholesterol-pooled-analysis-of-10-phase-3-odyssey-alirocumab-trials
#11
Harold E Bays, Robert S Rosenson, Marie T Baccara-Dinet, Michael J Louie, Desmond Thompson, G Kees Hovingh
PURPOSE: Clinical trials of statins and other lipid-lowering therapies (LLTs) often report large inter-individual variations in their effects on low-density lipoprotein cholesterol (LDL-C). We evaluated apparent hyporesponsiveness to the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab (defined as < 15% LDL-C reduction from baseline at all timepoints) using data from 10 Phase 3 trials (3120 hypercholesterolemic patients). METHODS: This report assessed the LDL-C percent reduction from baseline at weeks 4-104 (depending on study), and alirocumab serum levels and antidrug antibodies, in patients with apparent hyporesponsiveness...
April 7, 2018: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/29606415/effect-of-alirocumab-on-coronary-atheroma-volume-in-japanese-patients-with-acute-coronary-syndromes-and-hypercholesterolemia-not-adequately-controlled-with-statins-odyssey-j-ivus-rationale-and-design
#12
Junya Ako, Kiyoshi Hibi, Ken Kozuma, Katsumi Miyauchi, Yoshihiro Morino, Toshiro Shinke, Kenichi Tsujita, Kiyoko Uno, Yumiko Kawabata, Takafumi Hiro
BACKGROUND: Serial intravascular ultrasound (IVUS) imaging can be used to evaluate the effect of cholesterol-lowering on coronary atheroma progression and plaque volume, with evidence of potential incremental effects with more aggressive lipid-lowering treatments. Alirocumab is a highly specific, fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9). This study will investigate the effect of alirocumab on coronary artery plaque volume in Japanese patients with a recent acute coronary syndrome (ACS) and hypercholesterolemia while on stable statin therapy...
March 29, 2018: Journal of Cardiology
https://www.readbyqxmd.com/read/29526502/efficacy-and-safety-of-lipid-lowering-by-alirocumab-in-chronic-kidney-disease
#13
Peter P Toth, Jamie P Dwyer, Christopher P Cannon, Helen M Colhoun, Daniel J Rader, Ashish Upadhyay, Michael J Louie, Andrew Koren, Alexia Letierce, Jonas Mandel, Maciej Banach
Individuals with chronic kidney disease are at increased risk of premature cardiovascular disease. Among them, many with elevated low-density lipoprotein cholesterol (LDL-C) are unable to achieve optimal LDL-C on statins and require additional lipid-lowering therapy. To study this, we compared the LDL-C-lowering efficacy and safety of alirocumab in individuals with hypercholesterolemia with impaired renal function, defined as eGFR 30-59 ml/min/1.73 m2 , to those without impaired renal function eGFR ≥60 ml/min/1...
March 8, 2018: Kidney International
https://www.readbyqxmd.com/read/29525445/alirocumab-in-high-risk-patients-observations-from-the-open-label-expanded-use-program
#14
Charles J Glueck, Alan Brown, Anne C Goldberg, James M McKenney, Louis Kantaros, John Stewart, Joseph Elassal, Andrew Koren
BACKGROUND: The alirocumab expanded use program provided open-label access to alirocumab before its commercial availability to patients with severe hypercholesterolemia not controlled with maximally tolerated doses of standard-of-care lipid-lowering therapy. OBJECTIVE: To describe the safety and lipid-lowering efficacy of alirocumab in high-risk patients who were likely to be early users of proprotein convertase subtilisin/kexin type 9 inhibitors after approval...
February 7, 2018: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29498875/-the-role-of-pcsk9-inhibitors-and-of-lipoprotein-apheresis-in-the-treatment-of-homozygous-and-severe-heterozygous-familial-hypercholesterolemia-a-rivalry-or-are-things-quite-different
#15
Vladimír Bláha, Milan Bláha, Miriam Lánská, Eduard Havel, Pavel Vyroubal, Zdeněk Zadák, Pavel Žák
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...
2018: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/29493859/effect-of-alirocumab-on-lipids-and-lipoproteins-in-individuals-with-metabolic-syndrome-without-diabetes-pooled-data-from-10-phase-3-trials
#16
Robert R Henry, Dirk Müller-Wieland, Pam R Taub, Maja Bujas-Bobanovic, Michael J Louie, Alexia Letierce, Henry N Ginsberg
AIMS: This analysis assessed the efficacy and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, in patients with or without metabolic syndrome (MetS) using pooled data from 10 phase 3 ODYSSEY trials. MATERIALS AND METHODS: Data from 4983 randomized patients (1940 with MetS; 1642 with diabetes excluded) were assessed in subgroups by MetS status. Efficacy data were analysed in 4 pools per study design: 2 placebo-controlled pools (1 using alirocumab 150 mg every 2 weeks [Q2W], 1 using 75/150 mg Q2W) with background statin, and 2 ezetimibe-controlled pools (both alirocumab 75/150 mg Q2W), 1 with and 1 without background statin...
March 1, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29489129/-current-update-on-pcks9-inhibitors
#17
Baris Gencer, David Nanchen, Tinh-Hai Collet, Nicolas Rodondi, François Mach
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...
February 28, 2018: Revue Médicale Suisse
https://www.readbyqxmd.com/read/29472008/efficacy-and-safety-of-alirocumab-in-high-risk-patients-with-clinical-atherosclerotic-cardiovascular-disease-and-or-heterozygous-familial-hypercholesterolemia-from-5-placebo-controlled-odyssey-trials
#18
Peter A McCullough, Christie M Ballantyne, Santosh K Sanganalmath, Gisle Langslet, Seth J Baum, Prediman K Shah, Andrew Koren, Jonas Mandel, Michael H Davidson
Patients with previous atherosclerotic cardiovascular disease (ASCVD) and/or heterozygous familial hypercholesterolemia (HeFH) are at high risk of future cardiovascular events. Despite maximally tolerated doses of statins, many patients still have elevated low-density lipoprotein cholesterol (LDL-C) levels. We evaluated the efficacy and safety of alirocumab in patients with ASCVD and/or HeFH on a maximally tolerated dose of statin (rosuvastatin 20 or 40 mg, atorvastatin 40 or 80 mg, or simvastatin 80 mg, or lower doses with an investigator-approved reason) ± other lipid-lowering therapies from 5 placebo-controlled phase 3 trials (52 to 78 weeks)...
April 15, 2018: American Journal of Cardiology
https://www.readbyqxmd.com/read/29436756/alirocumab-vs-usual-lipid-lowering-care-as-add-on-to-statin-therapy-in-individuals-with-type-2-diabetes-and-mixed-dyslipidaemia-the-odyssey-dm-dyslipidemia-randomized-trial
#19
Kausik K Ray, Lawrence A Leiter, Dirk Müller-Wieland, Bertrand Cariou, Helen M Colhoun, Robert R Henry, Francisco J Tinahones, Maja Bujas-Bobanovic, Catherine Domenger, Alexia Letierce, Rita Samuel, Stefano Del Prato
AIM: To compare alirocumab, a proprotein convertase subtilisin-kexin type 9 inhibitor, with usual care (UC) in individuals with type 2 diabetes (T2DM) and mixed dyslipidaemia not optimally managed by maximally tolerated statins in the ODYSSEY DM-DYSLIPIDEMIA trial (NCT02642159). MATERIALS AND METHODS: The UC options (no additional lipid-lowering therapy; fenofibrate; ezetimibe; omega-3 fatty acid; nicotinic acid) were selected prior to stratified randomization to open-label alirocumab 75 mg every 2 weeks (with increase to 150 mg every 2 weeks at week 12 if week 8 non-HDL cholesterol concentration was ≥2...
June 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29411675/pcsk9-inhibitors-a-non-statin-cholesterol-lowering-treatment-option
#20
REVIEW
Gregory S Pokrywka
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...
April 2018: Postgraduate Medicine
keyword
keyword
37815
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"