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https://www.readbyqxmd.com/read/29038147/imputation-of-baseline-ldl-cholesterol-concentration-in-patients-with-familial-hypercholesterolemia-on-statins-or-ezetimibe
#1
Isabelle Ruel, Sumayah Aljenedil, Iman Sadri, Émilie de Varennes, Robert A Hegele, Patrick Couture, Jean Bergeron, Eric Wanneh, Alexis Baass, Robert Dufour, Daniel Gaudet, Diane Brisson, Liam R Brunham, Gordon A Francis, Lubomira Cermakova, James M Brophy, Arnold Ryomoto, G B John Mancini, Jacques Genest
BACKGROUND: Familial hypercholesterolemia (FH) is the most frequent genetic disorder seen clinically and is characterized by increased LDL cholesterol (LDL-C) (>95th percentile), family history of increased LDL-C, premature atherosclerotic cardiovascular disease (ASCVD) in the patient or in first-degree relatives, presence of tendinous xanthomas or premature corneal arcus, or presence of a pathogenic mutation in the LDLR, PCSK9, or APOB genes. A diagnosis of FH has important clinical implications with respect to lifelong risk of ASCVD and requirement for intensive pharmacological therapy...
October 16, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/29029165/depicting-new-pharmacological-strategies-for-familial-hypercholesterolaemia-involving-lipoprotein-a
#2
Alpo Vuorio, Gerald F Watts, Petri T Kovanen
Approximately 35 million people worldwide suffer from heterozygous familial hypercholesterolaemia (HeFH), a condition characterized by genetically determined life-long elevation of plasma low-density lipoprotein cholesterol (LDL-C). One in three of these patients also inherit an elevated plasma concentration of lipoprotein (a) [Lp(a)], a lipoprotein particle with atherogenic, inflammatory and prothrombotic properties. Accordingly, the combination of high plasma LDL-C and Lp(a) can markedly accelerate premature atherosclerotic cardiovascular disease (ASCVD)...
October 3, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28979175/recurrence-and-severe-worsening-of-hepatotoxicity-after-reintroduction-of-atorvastatin-in-combination-with-ezetimibe
#3
Silje Bergland Ellingsen, Elisabet Nordmo, Knut Tore Lappegård
Severe hepatotoxicity is a rare but well-known adverse reaction to statins. However, despite the widespread use of statins, only a few cases describing statin reexposure or switch to another statin after liver injury have been published. The literature on hepatotoxicity with ezetimibe alone or in combination with statins is also scarce. We report a case where a patient with a history of elevated liver enzymes while using atorvastatin, but prior and subsequent good tolerance to simvastatin and pravastatin, developed drug-induced liver injury on reexposure to a combination of atorvastatin and ezetimibe...
2017: Clinical Medicine Insights. Case Reports
https://www.readbyqxmd.com/read/28978219/epidemiology-and-management-of-hyperlipidemia
#4
Samantha Karr
Cardiovascular disease (CVD) is the leading cause of death among adults in the United States, and people with hyperlipidemia are at roughly twice the risk of developing CVD as compared to those with normal total cholesterol levels.1 Patients with familial hypercholesterolemia (FH) have an even greater risk of developing CVD at an earlier age; therefore, early detection and treatment are imperative to reduce cardiovascular events and premature death. Statins are the mainstay treatment for hyperlipidemia; however, the limitations of statins include treatment resistance, intolerance due to adverse events, and a lack of adherence which contribute to poor outcomes...
June 2017: American Journal of Managed Care
https://www.readbyqxmd.com/read/28972004/prevention-of-stroke-with-the-addition-of-ezetimibe-to-statin-therapy-in-patients-with-acute-coronary-syndrome-in-improve-it
#5
Erin A Bohula, Stephen D Wiviott, Robert P Giugliano, Michael A Blazing, Jeong-Gun Park, Sabina A Murphy, Jennifer A White, Francois Mach, Frans J Van de Werf, Anthony J Dalby, Harvey D White, Andrew M Tershakovec, Christopher P Cannon, Eugene Braunwald
Background -Patients who experience an acute coronary syndrome (ACS) are at heightened risk of recurrent ischemic events, including stroke. Ezetimibe improved cardiovascular outcomes when added to statin therapy in patients stabilized after ACS. We investigated the efficacy of the addition of ezetimibe to simvastatin for the prevention of stroke and other adverse cardiovascular events in IMPROVE-IT, with a focus on patients with a stroke prior to randomization. Methods -Post-ACS patients were randomized to placebo/simvastatin or ezetimibe/simvastatin and followed for a median of 6 years...
September 30, 2017: Circulation
https://www.readbyqxmd.com/read/28971955/systematic-review-and-network-meta-analysis-on-the-efficacy-of-evolocumab-and-other-therapies-for-the-management-of-lipid-levels-in-hyperlipidemia
#6
REVIEW
Peter P Toth, Gillian Worthy, Shravanthi R Gandra, Naveed Sattar, Sarah Bray, Lung-I Cheng, Ian Bridges, Gavin M Worth, Ricardo Dent, Carol A Forbes, Sohan Deshpande, Janine Ross, Jos Kleijnen, Erik S G Stroes
BACKGROUND: The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors evolocumab and alirocumab substantially reduce low-density lipoprotein cholesterol (LDL-C) when added to statin therapy in patients who need additional LDL-C reduction. METHODS AND RESULTS: We conducted a systematic review and network meta-analysis of randomized trials of lipid-lowering therapies from database inception through August 2016 (45 058 records retrieved). We found 69 trials of lipid-lowering therapies that enrolled patients requiring further LDL-C reduction while on maximally tolerated medium- or high-intensity statin, of which 15 could be relevant for inclusion in LDL-C reduction networks with evolocumab, alirocumab, ezetimibe, and placebo as treatment arms...
October 2, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28964736/efficacy-of-alirocumab-in-1191-patients-with-a-wide-spectrum-of-mutations-in-genes-causative-for-familial-hypercholesterolemia
#7
Joep C Defesche, Claudia Stefanutti, Gisle Langslet, Paul N Hopkins, Werner Seiz, Marie T Baccara-Dinet, Sara C Hamon, Poulabi Banerjee, John J P Kastelein
BACKGROUND: Mutation(s) in genes involved in the low-density lipoprotein receptor (LDLR) pathway are typically the underlying cause of familial hypercholesterolemia. OBJECTIVE: The objective of the study was to examine the influence of genotype on treatment responses with alirocumab. METHODS: Patients from 6 trials (n = 1191, including 758 alirocumab-treated; Clinicaltrials.gov identifiers: NCT01266876; NCT01507831; NCT01623115; NCT01709500; NCT01617655; NCT01709513) were sequenced for mutations in LDLR, apolipoprotein B (APOB), proprotein convertase subtilisin/kexin type 9 (PCSK9), LDLR adaptor protein 1, and signal-transducing adaptor protein 1 genes...
September 4, 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28940978/effects-of-short-term-add-on-ezetimibe-to-statin-treatment-on-expression-of-adipokines-and-inflammatory-markers-in-diabetic-and-dyslipidemic-patients
#8
Elizandra Silva Guimarães, Alvaro Cerda, Egidio Lima Dorea, Marcia Martins Silveira Bernik, Maria Cecilia Gusukuma, Gelba Almeida Pinto, Cristina Moreno Fajardo, Mario Hiroyuki Hirata, Rosario Dominguez Crespo Hirata
AIM: The influence of short term add-on ezetimibe to simvastatin treatment on expression of adipokines and inflammatory markers was investigated in diabetic and non-diabetic patients with hypercholesterolemia. METHOD: Hypercholesterolemic non-diabetic (HC, n=37) and diabetic (DM, n=47) patients were treated with simvastatin (SV, 10 or 20 mg/day/8-weeks) and then SV plus ezetimibe (SV+EZ, 10 mg each/day/4-weeks). Serum lipids, glycemic profile and inflammatory markers (hsCRP, adiponectin, resistin, VCAM-1 and ICAM-1) were evaluated before and after the add-on-ezetimibe therapy...
September 21, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28933629/ezetimibe-ameliorates-steatohepatitis-via-amp-activated-protein-kinase-tfeb-mediated-activation-of-autophagy-and-nlrp3-inflammasome-inhibition
#9
Soo Hyun Kim, Gyuri Kim, Dai Hoon Han, Milim Lee, Irene Kim, Bohkyung Kim, Kook Hwan Kim, Young-Mi Song, Jeong Eun Yoo, Hye Jin Wang, Soo Han Bae, Yong-Ho Lee, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha, Myung-Shik Lee
Impairment in macroautophagy/autophagy flux and inflammasome activation are common characteristics of nonalcoholic steatohepatitis (NASH). Considering the lack of approved agents for treating NASH, drugs that can enhance autophagy and modulate inflammasome pathways may be beneficial. Here, we investigated the novel mechanism of ezetimibe, a widely prescribed drug for hypercholesterolemia, as a therapeutic option for ameliorating NASH. Human liver samples with steatosis and NASH were analyzed. For in vitro studies of autophagy and inflammasomes, primary mouse hepatocytes, human hepatoma cells, mouse embryonic fibroblasts with Ampk or Tsc2 knockout, and human or primary mouse macrophages were treated with ezetimibe and palmitate...
October 3, 2017: Autophagy
https://www.readbyqxmd.com/read/28928170/effect-of-adding-bezafibrate-to-standard-lipid-lowering-therapy-on-post-fat-load-lipid-levels-in-patients-with-familial-dysbetalipoproteinemia-a-randomized-placebo-controlled-crossover-trial
#10
Charlotte Koopal, A David Marais, Jan Westerink, Yolanda van der Graaf, Frank L J Visseren
Familial dysbetalipoproteinemia (FD) is a genetic disorder associated with impaired postprandial lipid clearance. The effect of adding bezafibrate to standard lipid-lowering therapy on postprandial and fasting lipid levels in patients with FD is unknown. In this randomized, placebo-controlled, double blind, crossover trial, 15 patients with FD received bezafibrate and placebo for 6 weeks in randomized order in addition to standard lipid-lowering therapy (statin, ezetimibe and/or lifestyle). We assessed post-fat load lipids, expressed as (incremental) area under the curve (iAUC and AUC); as well as fasting levels and safety, and found that adding bezafibrate did not reduce post-fat load non-HDL-cholesterol (non-HDL-C) iAUC (1...
September 19, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28923989/competing-risks-of-cardiovascular-versus-noncardiovascular-death-during-long-term-follow-up-after-acute-coronary-syndromes
#11
Alexander C Fanaroff, Matthew T Roe, Robert M Clare, Yuliya Lokhnygina, Ann Marie Navar, Robert P Giugliano, Stephen D Wiviott, Andrew M Tershakovec, Eugene Braunwald, Michael A Blazing
BACKGROUND: Understanding the relative risk of cardiovascular versus noncardiovascular death is important for designing clinical trials. These risks may differ depending on patient age, sex, and type of acute coronary syndrome (ACS). METHODS AND RESULTS: IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) was a randomized controlled trial of simvastatin plus either ezetimibe or placebo following stabilized ACS. Cause of death was adjudicated by an independent committee...
September 18, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28922021/pharmacokinetic-drug-evaluation-of-ezetimibe-simvastatin-for-the-treatment-of-hypercholesterolemia
#12
REVIEW
Marilisa Bove, Federica Fogacci, Arrigo F G Cicero
Cholesterol lowering treatment is mainly based on statins eventually associated to adjunctive drugs of different class such as ezetimibe. In the present review, we analysed the pharmacokinetics, efficacy and safety of ezetimibe + simvastatin drug association. Areas covered: The bio-equivalence of ezetimibe and simvastatin when co-administrated in separate tablets or combined in a single pill is well documented. Ezetimibe is absorbed in small intestine, reaching peak plasma concentrations in 4-12 h, with a plasma half-life of 22 h...
October 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28915766/should-an-ldl-cholesterol-target-based-approach-be-readopted
#13
C Michael White, Erin R Weeda, Elaine Nguyen
OBJECTIVE: To review clinical trials driving the evolution of hyperlipidemic guidelines, discuss whether low-density lipoprotein (LDL) targets and adjunctive therapy on top of statins should be used, and summarize the pharmacist's role in helping achieve LDL goals. DATA SOURCES: MEDLINE search (1/1980-5/2017) using terms including LDL, lipid, and statin, with forward and backward citation tracking. STUDY SELECTION AND DATA EXTRACTION: English-language studies and guidelines assessing LDL-lowering therapy were included...
July 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28914630/strategies-for-the-use-of-nonstatin-therapies
#14
Angela Pirillo, Giuseppe D Norata, Alberico L Catapano
PURPOSE OF REVIEW: Dyslipidaemias are a major risk factor for cardiovascular disease (CVD); in particular, high levels of low-density lipoprotein cholesterol (LDL-C) have been associated to a higher cardiovascular risk. Reducing LDL-C levels decreases the risk of coronary heart disease (CHD), and the greater the LDL-C reduction, the greater the decrease in cardiovascular risk. Although statins represent the first line lipid-lowering therapy, many patients do not reach the recommended goals or exhibit adverse side effects leading to therapy discontinuation; in addition, a significant percentage of statin-treated patients continue to experience cardiovascular events even in the presence of well controlled LDL-C levels, because of alterations in other lipid/lipoprotein classes, including triglycerides and high-density lipoprotein cholesterol...
September 12, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28902717/new-approaches-to-address-dyslipidemia
#15
Klaus G Parhofer
PURPOSE OF REVIEW: Although lipid-lowering treatment with statins, ezetimibe, and PCSK9 inhibitors is a very successful strategy to prevent cardiovascular events, there is a need for further drug developments. Not all patients respond sufficiently to the available therapy (very high baseline values, intolerance). Furthermore, patients may be characterized by dyslipidemias not accessible to available drugs such as patients with homozygous familial hypercholesterolemia, chylomicronemia syndrome, or elevated lipoprotein(a)...
September 11, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28886926/2017-focused-update-of-the-2016%C3%A2-acc%C3%A2-expert-consensus-decision-pathway-on-the-role-of-non-statin-therapies-for-ldl-cholesterol-lowering-in%C3%A2-the-management-of-atherosclerotic-cardiovascular-disease-risk-a-report-of-the-american-college-of-cardiology-task-force
#16
Donald M Lloyd-Jones, Pamela B Morris, Christie M Ballantyne, Kim K Birtcher, David D Daly, Sondra M DePalma, Margo B Minissian, Carl E Orringer, Sidney C Smith
In 2016, the American College of Cardiology published the first expert consensus decision pathway (ECDP) on the role of non-statin therapies for low-density lipoprotein (LDL)-cholesterol lowering in the management of atherosclerotic cardiovascular disease (ASCVD) risk. Since the publication of that document, additional evidence and perspectives have emerged from randomized clinical trials and other sources, particularly considering the longer-term efficacy and safety of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors in secondary prevention of ASCVD...
October 3, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28884604/novel-treatment-options-for-the-management-of-heterozygous-familial-hypercholesterolemia
#17
Georgios Polychronopoulos, Konstantinos Tziomalos
Even though statins represent the mainstay of treatment of heterozygous familial hypercholesterolemia (FH), their low-density lipoprotein cholesterol (LDL-C) lowering efficacy is finite and most patients with FH will not achieve LDL-C targets with statin monotherapy. Addition of ezetimibe with or without bile acid sequestrants will also not lead to treatment goals in many of these patients, particularly in those with established cardiovascular disease. In this selected subgroup of the FH population, proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors provide substantial reductions in LDL-C levels, reduce cardiovascular morbidity and appear to be safe...
September 14, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28881270/molecular-and-clinical-characterization-of-a-series-of-patients-with-childhood-onset-lysosomal-acid-lipase-deficiency-retrospective-investigations-follow-up-and-detection-of-two-novel-lipa-pathogenic-variants
#18
Livia Pisciotta, Giulia Tozzi, Lorena Travaglini, Roberta Taurisano, Tiziano Lucchi, Giuseppe Indolfi, Francesco Papadia, Maja Di Rocco, Lorenzo D'Antiga, Patricia Crock, Komal Vora, Scott Nightingale, Helen Michelakakis, Anastasia Garoufi, Lilia Lykopoulou, Stefano Bertolini, Sebastiano Calandra
BACKGROUND AND AIMS: Childhood/Adult-onset Lysosomal Acid Lipase Deficiency (LAL-D) is a recessive disorder due to loss of function variants of LAL, the enzyme which hydrolyses cholesteryl esters, derived from internalized apoB containing lipoproteins. The disease is characterized by multi-organ involvement including the liver, spleen, intestine and cardiovascular system. The aim of this study was the clinical and molecular characterization of 14 (13 unrelated) previously unreported patients with childhood-onset LAL-D...
October 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28879791/incorporation-of-pcsk9-inhibitors-into-prevention-of-atherosclerotic-cardiovascular-disease
#19
Cezary Wójcik
Primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD) has become recently more complex than ever, leaving the clinicians perplexed with outdated guidelines and emerging evidence about new LDL-C lowering therapies. 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines have focused on high intensity statin therapy for specific groups of patients, while abandoning long established LDL-C goals, a strategy which no longer seems valid. PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors have emerged as the add-on therapy on top of statins and/or ezetimibe for the treatment of hypercholesterolemia and ASCVD prevention...
September 7, 2017: Postgraduate Medicine
https://www.readbyqxmd.com/read/28879192/unsuccessful-treatment-of-alopecia-areata-with-simvastatin-ezetimibe-experience-in-12-patients
#20
Mabe Freitas Gouveia, Ralph M Trüeb
BACKGROUND/AIMS: Alopecia areata is a common immune-mediated hair condition with limited treatment options and success rates. There is evidence that statins, which are used for reducing atherogenesis and cardiovascular disease, have immunomodulatory activities and therefore may also be used for treatment of selected dermatologic conditions, including alopecia areata. Among treatments evaluated for alopecia areata, oral simvastatin/ezetimibe therapy is currently under the scrutiny of expert opinion...
August 2017: Skin Appendage Disorders
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