DOCSLIB.ORG

What Are Effective Medication Combinations for Dyslipidemia?

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
What Are Effective Medication Combinations for Dyslipidemia? CLINICAL INQUIRIES What are effective medication combinations for dyslipidemia? Joseph Saseen, PharmD, FCCP, Elizabeth Tweed, BSN, MLIS University of Colorado at Denver and Health Sciences Center EVIDENCE- BASED ANSWER Many combination drug therapies are effective in effects for combined dyslipidemia (SOR: A). treating dyslipidemia. Compared with statin Most combination therapies increase the risk of monotherapy, combinations that include ezetimibe intolerance or side effects, including myopathy. (Zetia), a bile acid sequestrant, or niacin further The statin/gemfibrozil combination has the lower low-density lipoprotein (LDL) cholesterol highest risk of myopathy, whereas statin/ (strength of recommendation [SOR]: A), and ezetimibe or statin/bile acid sequestrant have the increase the likelihood of attaining National least increased risk (SOR: B). Studies evaluating Cholesterol Education Program (NCEP) LDL patient-oriented outcomes (morbidity, mortality) cholesterol goals (SOR: B). Adding ezetimibe to a with combination therapy vs monotherapy have bile acid sequestrant reduces LDL cholesterol not yet been conducted; however, combination (SOR: B). Fibrate or niacin added to statin® Dowdentherapies Health have Media demonstrated reduced athero- monotherapy provide mixed lipid-modifying sclerotic lesion progression. Copyrightor personal use only CLINICAL COMMENTARYF When statins alone don’t work, statin/fibrate combinations due to the interaction of think before writing a second prescription gemfibrozil with statins; plus, patients must forego When patients are unable to reach their lipid goal grapefruit juice with fibrates to avoid toxicity. on a single medication, they should first be Niacin has a low risk of toxicity, but fears of evaluated for dietary noncompliance before adding flushing may give patients pause (premedication another medication that can be difficult to manage. with aspirin can reduce flushing). Ezetimibe/statins Unfortunately, the older bile acid sequestrants are effective, have relatively low toxicity and are have multiple drug interactions (ie, warfarin, convenient due to availability of commercial digitalis, phenobarbital), and patients dislike them, combinations. When choosing medications, think since they must remember to take other medica- carefully about the patient before prescribing tions >1 hour before or >4 hours later (these another lipid-lowering medication. problems are not seen with colesevelam, a newer Paul Crawford, MD drug). Some physicians are reluctant to prescribe Eglin Air Force Base Family Medicine Residency, Eglin, Fla I Evidence summary may be needed to reach LDL cholesterol Hydroxymethyl glutaryl coenzyme A goals.1–4 Ezetimibe, niacin, and bile acid (HMG CoA) reductase inhibitors, better sequestrants (cholestyramine [Questran], known as statins (atorvastatin, fluva- colesevelam [WelChol], colestipol statin, lovastatin, rosuvastatin, prava- [Colestid]) have complementary effects statin, simvastatin), have been shown to that suggest they may be appropriate for lower LDL cholesterol in the primary use in combination with a statin. and secondary prevention of cardio- Adding a bile acid sequestrant to vascular disease. Although often effective statin monotherapy does not appear as monotherapy, combination regimens to increase the risk of systemic toxicity.5 70 VOL 55, NO 1 / JANUARY 2006 THE JOURNAL OF FAMILY PRACTICE For mass reproduction, content licensing and permissions contact Dowden Health Media. What are effective medication combinations for dyslipidemia? L A systematic review found that adding T ABLE colestipol or cholestyramine to a statin Commonly used combination therapies provides an additional 7% to 20% with estimated changes in lipid values absolute LDL cholesterol reduction.1 A randomized placebo-controlled trial CHANGE CHANGE CHANGE demonstrated that combination therapy COMBINATION IN LDL-C IN HDL-C IN TGD with colesevelam has similar effects. The absolute LDL cholesterol reduction of Statin/bile acid sequestrant iii h i with atorvastatin (Lipitor) alone (10 mg Statin/ezetimibe iii h i daily) increased from 38% to 48% after Statin/fibrate adding colesevelam 3.8 g daily (10% ii hh iii absolute LDL cholesterol reduction).6 Statin/niacin iii hhh iii Statin/ezetimibe combination thera- Ezetimibe/bile acid sequestrant py is FDA-approved, and provides an ii h i additional 12% to 21% absolute LDL Key: One arrow, small change; 2 arrows, moderate change; 3 arrows, large 2 change. LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density cholesterol reduction. Although consid- lipoprotein cholesterol; TGD, triglycerides ered safe, adding ezetimibe increases the incidence of elevated hepatic transami- nases from 0.4% to 1.3%.7 A double- erature.5 Accordingly, the maximum blind trial randomized 769 patients on approved daily doses of lovastatin statin monotherapy who were above (Mevacor), simvastatin (Zocor), and their NCEP LDL goal to either placebo rosuvastatin (Crestor) are lowered (20, or ezetimibe 10 mg daily.3 Absolute LDL 10, and 10 mg, respectively) when used cholesterol reductions were 25.1% with with gemfibrozil. ezetimibe vs 3.7% with placebo, and Adding niacin to statin monotherapy LDL goal attainment was 71.5% with can modify combined dyslipidemia as ezetimibe vs 18.9% with placebo (sec- does a statin/fibrate combination, by low- ondary endpoint). In one retrospective ering LDL cholesterol and triglycerides, analysis, ezetimibe provided a 19% and raising HDL cholesterol to an even FAST TRACK absolute LDL cholesterol reduction when greater extent. Patients are more intoler- Ezetimibe, niacin, added to a bile acid sequestrant.8 ant to a statin/niacin combination (eg, Combinations of statins with fibrates flushing) than to a statin/fibrate combina- and bile acid (fenofibrate [Tricor], gemfibrozil [Lopid]) tion, but have a lower risk of myopathy sequestrants have can treat combined dyslipidemia by with the former.5 The combination of complementary decreasing LDL cholesterol more than statin/niacin may be more desirable than 40%, decreasing triglycerides over 50%, statin/fibrate for patients with more effects in and raising high-density lipoprotein severe mixed dyslipidemia, especially combination (HDL) cholesterol more than 20%.9 those with very low HDL cholesterol val- with a statin Prospective controlled trials have shown ues, when monotherapy regimens are not regression of atherosclerotic lesions with completely effective. A fixed combination this combination, but have also shown of lovastatin with extended-release niacin increased risks of myopathy.6,10 In an (Advicor) is commercially available.4,11 analysis of 36 controlled clinical trials (1674 patients) that evaluated statin- Recommendations from others fibrate combinations, 0.12% of patients The NCEP Adult Treatment Panel III rec- developed myopathy, but none developed ommends adding a bile acid sequestrant, rhabdomyolysis or kidney failure.10 niacin, or ezetimibe to a statin when addi- Experts believe myopathy risk is greater tional LDL cholesterol-lowering is needed with gemfibrozil than fenofibrate, based to reach NCEP-III goals, and adding on gemfibrozil’s inhibition of statin glu- niacin or a fibrate to a statin to lower curonidation, and case reports in the lit- non-HDL cholesterol for patients with www. jfponline.com VOL 55, NO 1 / JANUARY 2006 71 CLINICAL INQUIRIES 12. Executive Summary of the Third Report of the persistently high triglycerides or low National Cholesterol Education Program (NCEP) HDL cholesterol.12,13 Expert Panel on Detection, Evaluation, and Treatment The American Association of Clinical of High Blood Cholesterol in Adults (Adult Treatment Endocrinologists also recommends using Panel III). JAMA 2001; 285:2486–2497. 13. Grundy SM, Cleeman JI, Merz CN, et al. Implications of these combinations for the following recent clinical trials for the National Cholesterol circumstances: severe dyslipidemia, inad- Education Program Adult Treatment Panel III guide- equate response to monotherapy, dose- lines. Circulation 2004; 110:227–239. dependent adverse effects, and certain 14. AACE medical guidelines for clinical practice for the 14 diagnosis and treatment of dyslipidemia and preven- mixed dyslipidemias. However, the clin- tion of atherogenesis. Endocr Pract 2000; 6:162–213. ical advisory on statins by American Heart Association/American College of Cardiology/National Heart, Lung and Blood Institute warns that statin/fibrate combinations (especially with gemfi- brozil) or statin/niacin (although rare) are risk factors for statin-associated myopathy.5 REFERENCES 1. Schectman G, Hiatt J. Dose-response characteristics of cholesterol-lowering drug therapies: implications for treatment. Ann Intern Med 1996; 125:990–1000. 2. Jeu L, Cheng JW. Pharmacology and therapeutics of ezetimibe (SCH 58235), a cholesterol-absorption inhibitor. Clin Ther 2003; 25:2352–2387. 3. Gagne C, Bays HE, Weiss SR, et al. Efficacy and safety of ezetimibe added to ongoing statin therapy for treat- ment of patients with primary hypercholesterolemia. Am J Cardiol 2002; 90:1084–1091. 4. Hunninghake DB, McGovern ME, Koren M, et al. A FAST TRACK dose-ranging study of a new, once-daily, dual-compo- nent drug product containing niacin extended-release Most combination and lovastatin. Clin Cardiol 2003; 26:112–118. therapies 5. Pasternak RC, Smith SC Jr, Bairey-Merz CN, Grundy SM, Cleeman JI, Lenfant C. ACC/AHA/NHLBI clinical increase risk advisory on the use and safety of statins. J Am Coll of side effects, Cardiol 2002; 40:567–572.
Load more

Recommended publications
  • Roszet (Rosuvastatin/Ezetimibe) – New Drug Approval
    Roszet (rosuvastatin/ezetimibe) – New drug approval • On March 23, 2021, the FDA approved Althera Pharmaceuticals’ Roszet (rosuvastatin/ezetimibe), in adults: as an adjunct to diet in patients with primary non-familial hyperlipidemia to reduce low- density lipoprotein cholesterol (LDL-C) and alone or as an adjunct to other LDL-C-lowering therapies in patients with homozygous familial hypercholesterolemia (HoFH) to reduce LDL-C. • Roszet is a combination tablet containing rosuvastatin, an HMG CoA-reductase inhibitor (statin), and ezetimibe, a dietary cholesterol absorption inhibitor. Both components are available generically. • The approval of Roszet was based on previous efficacy data with rosuvastatin and ezetimibe. • Roszet is contraindicated in patients with: — Acute liver failure or decompensated cirrhosis — Hypersensitivity to rosuvastatin, ezetimibe, or any excipients in Roszet. Hypersensitivity reactions including anaphylaxis, angioedema, and erythema multiforme have been reported. • Warnings and precautions for Roszet include myopathy and rhabdomyolysis, immune-mediated necrotizing myopathy, hepatic dysfunction, proteinuria and hematuria, and HbA1c and glucose levels. • The most common adverse reactions (> 2% and greater than statin alone) with ezetimibe co- administered with a statin are nasopharyngitis, myalgia, upper respiratory tract infection, arthralgia, diarrhea, back pain, influenza, pain in extremity, and fatigue. • The recommended dosage range of Roszet is 5 mg/10 mg to 40 mg/10 mg once daily. — The recommended dose of Roszet depends on a patient’s indication for usage, LDL-C, and individual risk for cardiovascular events. — The starting dosage for patients switching to Roszet from co-administration of a statin and ezetimibe is based on an equivalent dose of rosuvastatin and 10 mg of ezetimibe.
    [Show full text]
  • Effects of Pitavastatin, Atorvastatin, and Rosuvastatin on the Risk Of
    biomedicines Article Effects of Pitavastatin, Atorvastatin, and Rosuvastatin on the Risk of New-Onset Diabetes Mellitus: A Single-Center Cohort Study Wei-Ting Liu 1, Chin Lin 2,3,4, Min-Chien Tsai 5, Cheng-Chung Cheng 6, Sy-Jou Chen 7,8, Jun-Ting Liou 6 , Wei-Shiang Lin 6, Shu-Meng Cheng 6, Chin-Sheng Lin 6,* and Tien-Ping Tsao 6,9,* 1 Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan; [email protected] 2 School of Public Health, National Defense Medical Center, Taipei 11490, Taiwan; [email protected] 3 School of Medicine, National Defense Medical Center, Taipei 11490, Taiwan 4 Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 11490, Taiwan, 5 Department of Physiology and Biophysics, Graduate Institute of Physiology, National Defense Medical Center, Taipei 11490, Taiwan; [email protected] 6 Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan; [email protected] (C.-C.C.); [email protected] (J.-T.L.); [email protected] (W.-S.L.); [email protected] (S.-M.C.) 7 Department of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan; [email protected] 8 Graduate Institute of Injury Prevention and Control, College of Public Health and Nutrition, Taipei Medical University, Taipei 11031, Taiwan 9 Division of Cardiology, Cheng Hsin General Hospital, Taipei 11220, Taiwan * Correspondence: [email protected] (C.-S.L.); [email protected] (T.-P.T.); Tel.: +886-2-6601-2656 (C.-S.L.); +886-2-2826-4400 (T.-P.T.) Received: 25 October 2020; Accepted: 11 November 2020; Published: 13 November 2020 Abstract: Statins constitute the mainstay treatment for atherosclerotic cardiovascular disease, which is associated with the risk of new-onset diabetes mellitus (NODM).
    [Show full text]
  • Ezetimibe: a Novel Selective Cholesterol Absorption Inhibitor by Michele Koder, Pharm.D
    OREGON DUR BOARD NEWSLETTER A N E VIDENCE B ASED D RUG T HERAPY R ESOURCE COPYRIGHT 2003 OREGON STATE UNIVERSITY. ALL RIGHTS RESERVED Volume 5, Issue 2 Also available on the web and via e-mail list-serve at February 2003 http://pharmacy.orst.edu/drug_policy/newsletter_email.html Ezetimibe: A novel selective cholesterol absorption inhibitor By Michele Koder, Pharm.D. , OSU College of Pharmacy Ezetimibe (Zetia) is a novel selective cholesterol absorption inhibitor that was approved by the FDA in October 2002. Unlike statins (HMG-CoA reductase inhibitors) and bile acid sequestrants, ezetimibe does not inhibit hepatic cholesterol synthesis or increase bile acid secretion. In contrast, ezetimibe selectively inhibits the uptake of dietary cholesterol from enterocytes in the brush border of the intestinal lumen resulting in a decrease in the delivery of dietary cholesterol to the liver and a subsequent decrease in hepatic cholesterol stores and increased cholesterol clearance from the blood.1 Ezetimibe’s unique action has generated interest in its use in combination with other cholesterol-lowering agents. It is indicated for the treatment of primary hypercholesterolemia as monotherapy and in combination with a statin. Ezetimibe is also approved for homozygous familial hypercholesterolemia and homozygous sitosterolemia. TABLE 1: EZETIMIBE CLINICAL TRIAL SUMMARY Study / Design Population Treatment % Change LDL % Change HDL % Change TG Bays et al3 N=432 EZ 5 mg -15.7 +2.9 MC, R, DB, PC LDL 130-250mg/dl EZ 10 mg -18.5 +3.5 NS 12 wk; Phase II TG
    [Show full text]
  • Nustendi, INN-Bempedoic Acid, Ezetimibe
    Summary of risk management plan for Nustendi (Bempedoic acid/Ezetimibe) This is a summary of the risk management plan (RMP) for Nustendi. The RMP details important risks of Nustendi, how these risks can be minimized, and how more information will be obtained about Nustendi's risks and uncertainties (missing information). Nustendi's summary of product characteristics (SmPC) and its package leaflet give essential information to healthcare professionals and patients on how Nustendi should be used. This summary of the RMP for Nustendi should be read in the context of all this information, including the assessment report of the evaluation and its plain-language summary, all which is part of the European Public Assessment Report (EPAR). Important new concerns or changes to the current ones will be included in updates of Nustendi's RMP. I. The Medicine and What It Is Used For Nustendi is authorized for treatment of primary hypercholesterolemia in adults, as an adjunct to diet (see SmPC for the full indication). It contains bempedoic acid as the active substance and it is given by mouth. Further information about the evaluation of Nustendi’s benefits can be found in Nustendi’s EPAR, including in its plain-language summary, available on the EMA website, under the medicine’s webpage https://www.ema.europa.eu/en/medicines/human/EPAR/nustendi II. Risks Associated With the Medicine and Activities to Minimize or Further Characterize the Risks Important risks of Nustendi, together with measures to minimize such risks and the proposed studies for learning
    [Show full text]
  • Lipid Lowering Agents, Cognitive Decline, and Dementia: the Three-City Study
    Lipid lowering agents, cognitive decline, and dementia: the three-city study. Marie-Laure Ancelin, Isabelle Carrière, Pascale Barberger-Gateau, Sophie Auriacombe, Olivier Rouaud, Spiros Fourlanos, Claudine Berr, Anne-Marie Dupuy, Karen Ritchie To cite this version: Marie-Laure Ancelin, Isabelle Carrière, Pascale Barberger-Gateau, Sophie Auriacombe, Olivier Rouaud, et al.. Lipid lowering agents, cognitive decline, and dementia: the three-city study.: Lipid Lowering Agents and Cognitive Decline. Journal of Alzheimer’s Disease, IOS Press, 2012, 30 (3), pp.629-37. 10.3233/JAD-2012-120064. inserm-00707350 HAL Id: inserm-00707350 https://www.hal.inserm.fr/inserm-00707350 Submitted on 12 Jun 2012 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Lipid lowering agents, cognitive decline, and dementia: the three-city study Marie-Laure Ancelin 1 * , Isabelle Carrière 1 , Pascale Barberger-Gateau 2 , Sophie Auriacombe 2 , Olivier Rouaud 3 , Spiros Fourlanos 4 , Claudine Berr 1 , Anne-Marie Dupuy 1 5 , Karen Ritchie 1 6 1 Neuropsychiatrie : Recherche Epidémiologique
    [Show full text]
  • ADHD Parents Medication Guide Revised July 2013
    ADHD Parents Medication Guide Revised July 2013 Attention-Deficit/Hyperactivity Disorder Prepared by: American Academy of Child & Adolescent Psychiatry and American Psychiatric Association Supported by the Elaine Schlosser Lewis Fund Physician: ___________________________________________________ Address: ___________________________________________________ ___________________________________________________ ___________________________________________________ Phone: ___________________________________________________ Email: ___________________________________________________ ADHD Parents Medication Guide – July 2013 2 Introduction Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterized by difficulty paying attention, excessive activity, and impulsivity (acting before you think). ADHD is usually identified when children are in grade school but can be diagnosed at any time from preschool to adulthood. Recent studies indicate that almost 10 percent of children between the ages of 4 to 17 are reported by their parents as being diagnosed with ADHD. So in a classroom of 30 children, two to three children may have ADHD.1,2,3,4,5 Short attention spans and high levels of activity are a normal part of childhood. For children with ADHD, these behaviors are excessive, inappropriate for their age, and interfere with daily functioning at home, school, and with peers. Some children with ADHD only have problems with attention; other children only have issues with hyperactivity and impulsivity; most children with ADHD have problems with all three. As they grow into adolescence and young adulthood, children with ADHD may become less hyperactive yet continue to have significant problems with distraction, disorganization, and poor impulse control. ADHD can interfere with a child’s ability to perform in school, do homework, follow rules, and develop and maintain peer relationships. When children become adolescents, ADHD can increase their risk of dropping out of school or having disciplinary problems.
    [Show full text]
  • Pharmacy Prior Authorization Non-Formulary and Prior
    Pharmacy Prior Authorization Non-Formulary and Prior Authorization Guidelines Scroll down to see PA Criteria by drug class, or Ctrl+F to search document by drug name PA Guideline Requirements Duration of Approval if Requirements Are Met Non-Formulary Requests for Non-Formulary Medications that do not have specific Prior Authorization Initial Approval: Medication Guidelines will be reviewed based on the following: • Minimum of 3 months, Guideline • An appropriate diagnosis/indication for the requested medication, depending on the • An appropriate dose of medication based on age and indication, diagnosis, to determine • Documented trial of 2 formulary agents for an adequate duration have not been effective or adherence, efficacy and tolerated patient safety monitoring OR • All other formulary medications are contraindicated based on the patient’s diagnosis, other Renewal: medical conditions or other medication therapy, • Minimum of 6 months OR • Maintenance medications • There are no other medications available on the formulary to treat the patient’s condition may be approved Indefinite Maryland Physicians Care determines patient medication trials and adherence by a review of pharmacy claims data over the preceding twelve months. Additional information may be requested on a case-by-case basis to allow for proper review. Medications Requests for Medications requiring Prior Authorization (PA) will be reviewed based on the PA As documented in the requiring Prior Guidelines/Criteria for that medication. Scroll down to view the PA Guidelines for specific individual guideline Authorization medications. Medications that do not have a specific PA guideline will follow the Non-Formulary Medication Guideline. Additional information may be required on a case-by-case basis to allow for adequate review.
    [Show full text]
  • Fenofibrate Ezetimibe Studies
    FenofibrateFenofibrate EzetimibeEzetimibe SurrogateSurrogate TrialsTrials ThomasThomas Dayspring,Dayspring, MD,MD, FACPFACP Clinical Assistant Professor of Medicine University of Medicine and Dentistry of New Jersey Attending in Medicine: St Joseph’s Hospital, Paterson, NJ Certified Menopause Practitioner: North American Menopause Society North Jersey Institute of Menopausal Lipidology PharmacokineticPharmacokinetic DataData FenofibrateFenofibrate –– EzetimibeEzetimibe PharmacodynamicPharmacodynamic andand PharmacokineticPharmacokinetic InteractionInteraction StudyStudy Placebo (n = 8) Ezetimibe 10 mg (n = 8) Patients have no physical 30 activity and are on a high Fenofibrate 200 mg (n = 8) carbohydrate low fat diet which lowers HDL-C 20 Fenofibrate 200mg + 10 Ezetimibe 10 mg (n = 8) 0 -10 -20 -30 Change from Baseline (%) -40 -50 TC LDL-C HDL-C TG Mean (SE) percentage change from baseline in serum lipids on day 14 following oral administration of fenofibrate monotherapy, ezetimibe monotherapy, fenofibrate-ezetimibe co- administration therapy or placebo once daily to 14 healthy subjects with hypercholesterolemia Kosoglou T et al. Curr Med Res & Opin 2004;20:1185-1195 FenofibrateFenofibrate –– EzetimibeEzetimibe PharmacodynamicPharmacodynamic andand PharmacokineticPharmacokinetic InteractionInteraction StudyStudy Placebo (n = 8) 30 Ezetimibe 10 mg (n = 8) Fenofibrate 200 mg (n = 8) Combination therapy 20 produced significantly Fenofibrate 200mg + 10 Ezetimibe 10 mg (n = 8) greater reductions in 0 LDL-C and in small LDL-III -10 Levels of
    [Show full text]
  • Atorvastatin Slows the Progression of Cardiac Remodeling in Mice with Pressure Overload and Inhibits Epidermal Growth Factor Receptor Activation
    335 Hypertens Res Vol.31 (2008) No.2 p.335-344 Original Article Atorvastatin Slows the Progression of Cardiac Remodeling in Mice with Pressure Overload and Inhibits Epidermal Growth Factor Receptor Activation Yulin LIAO1), Hui ZHAO2), Akiko OGAI1), Hisakazu KATO2), Masanori ASAKURA1), Jiyoong KIM1), Hiroshi ASANUMA1), Tetsuo MINAMINO2), Seiji TAKASHIMA2), and Masafumi KITAKAZE1) The aim of this study was to investigate whether atorvastatin inhibits epidermal growth factor receptor (EGFR) activation in cardiomyocytes in vitro and slows the progression of cardiac remodeling induced by pressure overload in mice. Either atorvastatin (5 mg/kg/day) or vehicle was orally administered to male C57BL/6J mice with transverse aortic constriction (TAC). Physiological parameters were obtained by echocardiography or left ventricular (LV) catheterization, and morphological and molecular parameters of the heart were also examined. Furthermore, cultured neonatal rat cardiomyocytes were studied to clarify the underlying mechanisms. Four weeks after TAC, atorvastatin reduced the heart/body weight and lung/body weight ratios (8.69±0.38 to 6.45±0.31 mg/g (p<0.001) and 10.89±0.68 to 6.61±0.39 mg/g (p<0.01) in TAC mice with and without atorvastatin, respectively). Decrease of LV end-diastolic pressure and the time con- stant of relaxation, increased fractional shortening, downregulation of a disintegrin and metalloproteinase (ADAM)12, ADAM17 and heparin-binding epidermal growth factor genes, and reduction of the activity of EGFR and extracellular signal–regulated kinase (ERK) were observed in the atorvastatin group. Phenyleph- rine-induced protein synthesis, phosphorylation of EGFR, and activation of ERK in neonatal rat cardiomyo- cytes were all inhibited by atorvastatin.
    [Show full text]
  • Role of Colesevelam in Combination Lipid-Lowering Therapy
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Springer - Publisher Connector Am J Cardiovasc Drugs (2013) 13:315–323 DOI 10.1007/s40256-013-0037-0 REVIEW ARTICLE Role of Colesevelam in Combination Lipid-Lowering Therapy Michael R. Jones • Oliseyenum M. Nwose Published online: 3 August 2013 Ó The Author(s) 2013. This article is published with open access at Springerlink.com Abstract Hyperlipidemia is associated with an increased ezetimibe, statin plus niacin, or statin plus ezetimibe) and risk of cardiovascular events; reducing low-density lipo- high-sensitivity C-reactive protein (with statins), and protein cholesterol (LDL-C), the primary target for cho- increases in apo A-I (with statins, ezetimibe, or statins plus lesterol-lowering therapy, lowers the risk for such events. niacin). Triglyceride levels remained relatively unchanged Although bile acid sequestrants were the first class of drugs when colesevelam was combined with statins, fibrates, to show a mortality benefit related to LDL-C lowering, ezetimibe, or statin plus ezetimibe, and decreased with the statins are now considered first-line pharmacological ther- triple combination of colesevelam, statin, and niacin. apy for reducing LDL-C levels because of their potency Colesevelam offset the negative glycemic effects of statins and their remarkable record of successful outcomes studies. and niacin in subjects with insulin resistance or impaired Nevertheless, a substantial proportion of patients do not glucose tolerance. Colesevelam was generally well toler- achieve LDL-C goals with statin monotherapy. In addition, ated when added to other lipid-lowering therapies in clin- because of adverse effects (primarily myopathy), some ical trials, with gastrointestinal effects such as constipation patients may be unwilling to use or unable to tolerate statin being the predominant adverse events.
    [Show full text]
  • Cholestagel®) Combination and Monotherapy for Familial Hypercholesterolaemia
    New Medicine Recommendation Colesevelam (Cholestagel®) Combination and monotherapy for familial hypercholesterolaemia Recommendation: Black - NOT recommended for use by the NHS in Lancashire. Colesevelam (Cholestagel®) is NOT recommended as combination or monotherapy for familial hypercholesterolaemia. Clinical evidence indicates that the drug is poorly tolerated and the trials were weak in significant areas such as the inclusion of small numbers of patients, only demonstrating surrogate endpoints or being conducted using nonstandard co-administered drugs. There are similar, established drugs for the treatment of the condition for which there were no head to head trials with Colesevalam therefore relative clinical efficacy cannot be directly demonstrated. Summary of supporting evidence: Primary dyslipidaemias, including familial hypercholesterolaemia (FH), are lipid disorders that are genetic in origin. FH is the most common inherited lipid metabolism disorder in its heterozygous form. In the UK heterozygous FH affects 1 in 500 of the UK population. [1] Statin therapy is the first-line treatment for patients with the vast majority of dyslipidaemias. NICE CG 71 recommends the prescribing of a high-intensity statin at the maximum licensed dose or at the maximum tolerated dose to achieve a reduction in LDL cholesterol concentration of greater than 50% from baseline. [2] Colesevelam is a lipid-lowering polymer that binds bile acids in the intestine, impeding their reabsorption. [3] Colesevelam is a third-line agent, behind statins and ezetimibe. [2] The main body of evidence for the use of colesevelam in familial hypercholesterolaemia comes from the European Public Assessment Reports (EPAR). Study GTC-48-301 was a randomised, double-blind, parallel design, placebo-controlled pivotal phase III dose-response study.
    [Show full text]
  • FIELD Study Revealed Fenofibrate Reduced Need for Laser Treatment for Diabetic Retinopathy by Anthony C
    Supplement to Supported by an unrestricted educational grant from Abbott Laboratories March/April 2008 FIELD Study Revealed Fenofibrate Reduced Need for Laser Treatment for Diabetic Retinopathy By Anthony C. Keech, MBBS, Msc Epid, FRANZCS, FRACP; and Paul Mitchell, MBBS(Hons), MD, PhD, FRANZCO, FRACS, FRCOphth, FAFPHM This agent’s mechanism of benefit in diabetic retinopathy appears to go beyond its effects on lipid concentration or blood pressure, and this potential mechanism of action operates even when glycemic control and blood pressure levels are within goal. ABSTRACT icant relative reduction was seen of almost one-third in PURPOSE the rate of first laser application for retinopathy after The FIELD (Fenofibrate Intervention and Event an average treatment duration of 5 years with fenofi- Lowering in Diabetes) study sought to investigate brate 200 mg/day. whether long-term lipid-lowering therapy with fenofi- In this report, we detail the effects of fenofibrate brate would reduce macro- and microvascular compli- administration on ophthalmic microvascular compli- cations among patients with type 2 diabetes. We previ- cations and attempt to clarify some of the underlying ously reported that in type 2 diabetes patients with pathologies being addressed among patients undergo- adequate glycemic and blood pressure control, a signif- ing laser treatment. Jointly sponsored by The Dulaney Foundation and Retina Today MARCH/APRIL 2008 I SUPPLEMENT TO RETINA TODAY I 1 FIELD Study Revealed Fenofibrate Reduced Need for Laser Treatment for Diabetic Retinopathy Jointly sponsored by The Dulaney Foundation and Retina Today. Release date: April 2008. Expiration date: April 2009. This continuing medical education activity is supported by an unrestricted educational grant from Abbott Laboratories.
    [Show full text]