DOCSLIB.ORG

Comparative Study Between High-Dose Fluvastatin and Low-Dose

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Comparative Study Between High-Dose Fluvastatin and Low-Dose Endocrine Journal 2011, 58 (3), 171-175 ORIGINAL Comparative study between high-dose fluvastatin and low- dose fluvastatin and ezetimibe with regard to the effect on endothelial function in diabetic patients Yoshiaki Kawagoe, Yoshiyuki Hattori, Ayuko Nakano, Chie Aoki, Seiichi Tanaka, Satoshi Ohta, Toshie Iijima, Atsuko Tomizawa, Teruo Jojima, Hiroyuki Kase and Kikuo Kasai Department of Endocrinology and Metabolism, Dokkyo University School of Medicine, Mibu, Japan Abstract. It is well established that statins improve the prognosis of patients with coronary artery disease. However, it is still unclear whether the protective effects of statins relate to lipid lowering alone or whether other pleiotropic effects may contribute. Thus, we compared the endothelial function among two groups of diabetic patients treated with fluvastatin 60 mg (F60) or fluvastatin 20 mg combined with ezetimibe 10 mg (F20/E10). The endothelial function was evaluated by measuring flow-mediated vasodilatation (FMD) at baseline and follow-up at 10 weeks. Similar improvements in FMD were observed in the two groups. The reduction in low-density lipoprotein cholesterol (LDL-C) was less pronounced in the F60 group, compared with the F20/E10 group. A significant reduction in remnant-like lipoprotein particles cholesterol (RLP-C) was observed in the F20/E10 group, but not in the F60 group. A correlation between the observed reduction in LDL-C or RLP-C and the improvement in FMD was observed in F20/E10 group. These results suggest that high-dose fluvastatin might have pleiotropic effects of potential clinical benefit, and that the combination of ezetimibe with a reduced dose of fluvastatin may also significantly improve endothelial function with reduction of LDL-C and RLP-C. Key words: Statin, Endothelial function, Pleiotropic effects, Diabetes CHOLESTEROL-LOWERING therapy with 3-hy- simvastatin 80 mg or a combination of simvastatin 10 droxymethlglutaryl coenzyme A reductase inhibitors mg and ezetimibe 10 mg. The observed improvements (statins) decreases mortality and morbidity in patients in endothelial function did not differ significantly with cardiovascular disease, particularly in patients with between the two groups. Likewise, similar reductions type 2 diabetes mellitus [1, 2]. However, it remains in LDL-C were observed among the two groups (45% uncertain whether the protective effects of statins relate to 50%), suggesting that the lipid-lowering effect of to their lipid-lowering effect alone, or whether other therapy might be a more important mediator of flow- pleiotropic effects may contribute. Experimental data mediated dilation than pleiotropic effects. In another suggest that statins have pleiotropic effects, but the study, Liu et al. [5] compared the effect of simvasta- clinical relevance of these effects remains uncertain. tin 40 mg daily, and a combination of simvastatin 10 Since ezetimibe has been observed to provide signif- mg and ezetimibe 10 mg daily, with placebo in three icant incremental reductions in low-density lipoprotein groups of patients with low-density lipoprotein choles- cholesterol (LDL-C) when co-administered with statin terol readings >130 mg/dL and less than two cardiovas- therapy [3], Settergren et al. [4] compared the endothe- cular risk factors. The groups were compared based on lial function of two groups of patients with dysgly- relative changes in Rho-associated coiled-coil contain- cemia and coronary artery disease treated with either ing protein kinase activity as the primary endpoint, and endothelial function as a secondary endpoint. They Received Oct. 1, 2010; Accepted Jan. 4, 2011 as K10E-289 Released online in J-STAGE as advance publication Feb. 4, 2011 concluded that high-dose statin monotherapy induced Correspondence to: Yoshiyuki Hattori, Department of a greater reduction in Rho-associated coiled-coil con- Endocrinology and Metabolism, Dokkyo University School of taining protein kinase activity and improved endothe- Medicine, Mibu, Japan. E-mail: [email protected] lial function as measured by flow-mediated dilation, ©The Japan Endocrine Society 172 Kawagoe et al. compared with combination therapy of a low-dose sta- Table 1 Lipid, CRP and HbA1c at baseline and follow-up tin with ezetimibe. The authors feel this suggests ben- F60 (n=12) Baseline Follow-up p eficial pleiotropic effects of statins in humans. total cholesterol 236±33 186±23 <0.005 In addition to these studies, a number of other stud- LDL-C 154±26 106±15 <0.005 ies have investigated the pleiotropic effects of statins HDL-C 55.4±16 58.1±18 0.16 with varying results [4-7]. These results stress the Triglyceride 115±28.9 102±28.6 0.07 need for mechanistic study of an individual statin and RLP-C 7.18±2.48 5.78±1.99 0.16 multicenter study examining whether there is a clini- C-reactive protein 1.23±1.1 0.58±0.54 <0.05 cal benefit of a particular statin beyond its lipid-low- HbA1c 6.17±0.86 6.49±1.05 0.07 ering effect. In the present study, we tested diabetic F20/E10 (n=12) Baseline Follow-up p patients with high-dose fluvastatin or a combination of total cholesterol 244±36 176±23 <0.005 low-dose fluvastatin with ezetimibe. One of a num- LDL-C 164±33 96±22 <0.005 ber of statins that have been introduced to the market, HDL-C 57.2±18 60.5±20 0.12 fluvastatin appears to act directly on the blood vessel Triglyceride 128±57.9 94±29.3 0.06 wall to stabilize plaques in situ (agents that share this RLP-C 10.55±4.88 5.86±4.30 <0.005 property have been termed vascular statins). We have C-reactive protein 1.01±0.61 0.42±0.33 <0.05 recently reported a protective effect of fluvastatin on HbA1c 6.50±0.62 6.77±0.72 0.06 vascular endothelial cells, despite its less potent cho- lesterol-lowering effect in diabetic patients [8]. When co-administered with statin therapy, ezetimibe has dard linear regression methods. A value of p<0.05 been reported to provide significant incremental reduc- was considered statistically significant. The study tions in LDL-C and TG, as well as increases in HDL-C. was carried out in accordance with the Declaration of Thus, we compared the endothelial function among Helsinki (2000) of the World Medical Association, and two groups of diabetic patients with fluvastatin 60 mg was approved by the Ethics Committees of the hospi- or fluvastatin 20 mg combined with ezetimibe 10 mg. tal. Written informed consent was obtained from each patient after full explanation of the purpose, nature and Materials and Methods risk of the procedure. Hypercholesterolemic patients were randomly Results assigned to receive 60 mg fluvastatin (the F60 group: 12 diabetic patients) or 20 mg fluvastatin combined The two groups were well balanced with regard to with ezetimibe 10 mg (the F20/E10 group: 10 dia- age (F60: 65.1 ± 7.2 years vs. F20/E10: 64.2 ± 7.2 betic and 2 IGT patients) for 10 weeks, and measured years) and gender (male: F60 5/12 vs. F20/E10 6/12). flow-mediated vasodilatation (FMD), total cholesterol All patients in the F60 group were diabetics, while the (TC), LDL-cholesterol (LDL-C), HDL-cholesterol F20/E10 group contained 10 diabetics and two patients (HDL-C), triglyceride (TG), remnant-like lipopro- with IGT. tein particles cholesterol (RLP-C), and high-sensitiv- As shown in Table 1, TC (mg/dL) decreased from ity (hs) C-reactive protein (CRP). FMD following 236 ± 33 to 186 ± 23 and LDL-C (mg/dL) decreased forearm ischemia of the brachial artery and also nitro- from 154 ± 26 to 106 ± 15 in the F60 group, while glycerine-induced vasodilatation of the brachial artery TC decreased from 244 ± 36 to 176 ± 23 and LDL-C were assessed in a high-resolution ultrasound system decreased from 164 ± 33 to 96 ± 22 in the F20/E10 equipped with 2-dimensional imaging software with a group. The decrease in LDL-C in the F60 group was pulse Doppler flow velocimeter (Unex, Tokyo, Japan). 42.7 ± 22.7, while that in the F20/E10 group was 64.8 The study was performed in the morning under fast- ± 17.3 (p<0.05 compared with F60). The observed ing conditions, after resting quietly for 30 minutes in a changes in HDL-C and TG were not statistically signif- light- and temperature-controlled room. Data are pre- icant in either group. A significant reduction in RLP-C sented as the mean ± SD. Comparisons of data were was observed in the F20/E10 group, while there was performed by paired or unpaired Student’s t-test, and no significant change in RLP-C in the F60 group. A the correlation coefficient was determined using stan- significant reduction in hsCRP was observed in both Cholesterol and endothelial function 173 Fig. 1 Absolute changes in flow-mediated endothelium- dependent vasodilatation (dFMD) in the F60 and F20/E10 group from baseline to follow-up. Data are depicted as medians and quartiles; n = 12 in the F60 group and n = 12 in the F20/E10 group. groups. HbA1c was not affected in either group. An improvement in FMD from 5.01% ± 1.59% to 7.29% ± 3.14% (p<0.05) was observed in the F60 group, while an improvement in FMD from 5.43% ± Fig. 2 Correlation of change in LDL-C (dLDL) and change in 2.25% to 7.61% ± 2.56% (p<0.005) was observed in FMD (dFMD) were presented in the F60 (A) and F20/ the F20/E10 group (Fig. 1). Endothelium-independent E10 (B) group from baseline to follow-up. p=0.5962 in vasodilation (nitroglycerin-induced dilation) did not (A), p=0.0472 in (B).
Load more

Recommended publications
  • 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]
  • Zetia® (Ezetimibe) Tablets
    29480958T REV 14 ZETIA® (EZETIMIBE) TABLETS DESCRIPTION ZETIA (ezetimibe) is in a class of lipid-lowering compounds that selectively inhibits the intestinal absorption of cholesterol and related phytosterols. The chemical name of ezetimibe is 1-(4-fluorophenyl)- 3(R)-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4(S)-(4-hydroxyphenyl)-2-azetidinone. The empirical formula is C24H21F2NO3. Its molecular weight is 409.4 and its structural formula is: OH OH S SR N F F O Ezetimibe is a white, crystalline powder that is freely to very soluble in ethanol, methanol, and acetone and practically insoluble in water. Ezetimibe has a melting point of about 163°C and is stable at ambient temperature. ZETIA is available as a tablet for oral administration containing 10 mg of ezetimibe and the following inactive ingredients: croscarmellose sodium NF, lactose monohydrate NF, magnesium stearate NF, microcrystalline cellulose NF, povidone USP, and sodium lauryl sulfate NF. CLINICAL PHARMACOLOGY Background Clinical studies have demonstrated that elevated levels of total cholesterol (total-C), low density lipoprotein cholesterol (LDL-C) and apolipoprotein B (Apo B), the major protein constituent of LDL, promote human atherosclerosis. In addition, decreased levels of high density lipoprotein cholesterol (HDL-C) are associated with the development of atherosclerosis. Epidemiologic studies have established that cardiovascular morbidity and mortality vary directly with the level of total-C and LDL-C and inversely with the level of HDL-C. Like LDL, cholesterol-enriched triglyceride-rich lipoproteins, including very-low- density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), and remnants, can also promote atherosclerosis. The independent effect of raising HDL-C or lowering triglycerides (TG) on the risk of coronary and cardiovascular morbidity and mortality has not been determined.
    [Show full text]
  • Bempedoic Acid) Tablets, for Oral Use Most Common (Incidence ≥ 2% and Greater Than Placebo) Adverse Reactions Initial U.S
    HIGHLIGHTS OF PRESCRIBING INFORMATION • Tendon Rupture: Tendon rupture has occurred. Discontinue NEXLETOL These highlights do not include all the information needed to use at the first sign of tendon rupture. Avoid NEXLETOL in patients who NEXLETOL™ safely and effectively. See full prescribing information have a history of tendon disorders or tendon rupture. (5.2) for NEXLETOL. --------------------------------ADVERSE REACTIONS----------------------------­ NEXLETOL (bempedoic acid) tablets, for oral use Most common (incidence ≥ 2% and greater than placebo) adverse reactions Initial U.S. Approval: 2020 are upper respiratory tract infection, muscle spasms, hyperuricemia, back pain, abdominal pain or discomfort, bronchitis, pain in extremity, anemia, ----------------------------INDICATIONS AND USAGE--------------------------­ and elevated liver enzymes. (6.1) NEXLETOL is an adenosine triphosphate-citrate lyase (ACL) inhibitor indicated as an adjunct to diet and maximally tolerated statin therapy for the To report SUSPECTED ADVERSE REACTIONS, contact Esperion at treatment of adults with heterozygous familial hypercholesterolemia or 833-377-7633 (833 ESPRMED) or FDA at 1-800-FDA-1088 or established atherosclerotic cardiovascular disease who require additional www.fda.gov/medwatch. lowering of LDL-C. (1) --------------------------------DRUG INTERACTIONS----------------------------­ Limitations of Use: The effect of NEXLETOL on cardiovascular morbidity • Simvastatin: Avoid concomitant use of NEXLETOL with simvastatin and mortality has not been
    [Show full text]
  • Bempedoic Acid and Inclisiran for Patients with Heterozygous Familial Hypercholesterolemia and for Secondary Prevention of ASCVD: Effectiveness and Value
    Bempedoic Acid and Inclisiran for Patients with Heterozygous Familial Hypercholesterolemia and for Secondary Prevention of ASCVD: Effectiveness and Value Draft Evidence Report November 12, 2020 Prepared for ©Institute for Clinical and Economic Review, 2020 ICER Staff and Consultants Modeling Team Grace A. Lin, MD, MAS Dhruv S. Kazi, MD, MSc, MS Associate Professor of Medicine and Health Policy Associate Director, Smith Center for Outcomes University of California, San Francisco Research in Cardiology Director, Cardiac Critical Care Unit Jane Jih, MD, MPH Beth Israel Deaconess Medical Center Assistant Professor, Division of General Internal Associate Professor, Harvard Medical School Medicine University of California, San Francisco Foluso Agboola, MBBS, MPH Director, Evidence Synthesis Dr. Kazi was responsible for the development of the ICER cost-effectiveness model, interpretation of results, and drafting of the economic sections of this report; the Rick Chapman, PhD, MS resulting ICER reports do not necessarily represent the Director of Health Economics views of Beth Israel Deaconess Medical Center or ICER Harvard Medical School. Steven D. Pearson, MD, MSc President ICER DATE OF PUBLICATION: November 12, 2020 How to cite this document: Lin GA, Kazi DS, Jih J, Agboola F, Chapman R, Pearson SD. Inclisiran and Bempedoic Acid for Patients with Heterozygous Familial Hypercholesterolemia and for Secondary Prevention of ASCVD: Effectiveness and Value; Draft Evidence Report. Institute for Clinical and Economic Review, November 12, 2020. https://icer-review.org/material/high-cholesterol-update- draft-evidence-report/ Grace Lin served as the lead author for the report and wrote the background, other benefits, and contextual considerations sections of the report, with Jane Jih serving as a co-author.
    [Show full text]
  • Pitavastatin (Livalo) Have Not Been Shown to Decrease LDL-C More Doses of Other Statins and No Data Are Available on Clinical Outcomes with Pitavastatin
    Livalo (Pitavastatin) Thomas Dayspring MD, FACP, FNLA 1) LIVALO DISCUSSION: Although new to the US pitavastatin has been used in Japan for many years with great safety (in a population fairly sensitive to statins). Because it binds much more completely with HMG CoA reductase than other statins, it takes a much less concentration compared to other statins to inhibit cholesterol synthesis (thus it is marketed at 1, 2 and 4 mg rather than the usual 10, 20, and 40 mg). The best and most current review of it I have seen is from Clin. Lipidol. (2010) 5(3), 309–323 where all statins are compared on all clinically important pharmacokinetic and pharmacodynamic parameters. The author concludes: "Pitavastatin is a novel statin that induces plaque regression (IVUS Study) and is non- inferior to atorvastatin and, on some measures, superior to simvastatin and to pravastatin in the elderly. Pitavastatin addresses non-LDL-C risk factors, including producing sustained increases in HDL-C levels. Both the pitavastatin molecule and the lactone metabolite undergo very little metabolism by CYP3A4 and, therefore, unlike some other statins, does not interact with CYP3A4 substrates. It is the least lipophilic statin and thus requires like rosuvastatin various ABC transporters and solute carriers like organic anion transporters to get in and out of cells and thus there are potential interactions (as with most other statins) with erythromycin, cyclosporine, gemfibrozil, ritonavir/lopinavir etc. It's LDL-C lowering ability is in the Lipitor 20-40 mg range with a 30-40% range (depending on the dose used) and is somewhat more effective at raising HDL-C and apoA-I than other statins: the mechanism is it stimulates apoA-I production and ABCA1 upregulation (Biochemical and Biophysical Research Communications 324 (2004) 835–839).
    [Show full text]
  • CP.PMN.237 Bempedoic Acid (Nexletol)
    Clinical Policy: Bempedoic Acid (Nexletol), Bempedoic Acid/Ezetimibe (Nexlizet) Reference Number: CP.PMN.237 Effective Date: 09.01.20 Last Review Date: 02.21 Revision Log Line of Business: Commercial, HIM, Medicaid See Important Reminder at the end of this policy for important regulatory and legal information. Description The following are adenosine triphosphate-citrate lyase (ACL) inhibitors requiring prior authorization: bempedoic acid (Nexletol™) and bempedoic acid/ezetimibe (Nexlizet™). Nexlizet contains ezetimibe, which is a cholesterol absorption inhibitor. FDA Approved Indication(s) Nexletol and Nexlizet are indicated for use as adjuncts to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or established atherosclerotic cardiovascular disease (ASCVD) who require additional lowering of low-density lipoprotein cholesterol (LDL-C). Limitation(s) of use: The effect of Nexletol and Nexlizet on cardiovascular morbidity and mortality has not been determined. Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria. It is the policy of health plans affiliated with Centene Corporation® that Nexletol and Nexlizet are medically necessary when the following criteria are met: I. Initial Approval Criteria A. Heterozygous Familial Hypercholesterolemia and Atherosclerotic Cardiovascular Disease (must meet all): 1. Diagnosis of one of the following (a or b): a. ASCVD as evidenced by a history of any one of the following conditions (i-vii): i. Acute coronary syndromes; ii. Clinically significant coronary heart disease (CHD) diagnosed by invasive or noninvasive testing (such as coronary angiography, stress test using treadmill, stress echocardiography, or nuclear imaging); iii.
    [Show full text]
  • Effects of Fluvastatin on Insulin Resistance and Cardiac Morphology in Hypertensive Patients
    Journal of Human Hypertension (2011) 25, 492–499 & 2011 Macmillan Publishers Limited All rights reserved 0950-9240/11 www.nature.com/jhh ORIGINAL ARTICLE Effects of fluvastatin on insulin resistance and cardiac morphology in hypertensive patients AA Teixeira, A Buffani, A Tavares, AB Ribeiro, MT Zanella, O Kohlmann Jr and MC Batista Division of Nephrology, Hypertension and Cardiovascular Metabology Center, Kidney and Hypertension Hospital, Federal University of Sa˜o Paulo, Sa˜o Paulo, Brazil Among hypertensive patients, cardiovascular disease resting systolic blood pressure. However, maximum morbidity is common, even in those who are adequately systolic EBP was lower in the treatment group than in treated. New pharmacological strategies to mitigate the the placebo group (175±18 vs 192±23 mm Hg, Po0.05), burden of arterial hypertension are needed. This 12- as was left ventricular mass index (LVMI; 82±15 vs month, randomized, double-blind placebo-controlled 100±23, Po0.05), and HOMA-IR index was lower after study investigated the effect of statin (fluvastatin) fluvastatin treatment (2.77±1.46 vs 3.33±1.73, Po0.05). treatment on ambulatory blood pressure (ABP), exercise Changes in lipid profile were not correlated with blood blood pressure (EBP), myocardial structure, endothelial pressure, endothelial function, LVMI or HOMA-IR data. function and insulin resistance in 50 hypertensive In hypertensive patients, fluvastatin can improve max- patients. At baseline, the groups were comparable in imum systolic EBP, myocardial remodelling and insulin terms of demographic characteristics, ABP, EBP, en- resistance, independently of lipid profile variations and dothelial function and homeostasis model assessment endothelial function. of insulin resistance (HOMA-IR).
    [Show full text]
  • NCEP Drug Treatment
    NCEP Drug Treatment The information contained in this document is taken directly from the National Cholesterol Education Program, Adult Treatment Panel III (NCEP, ATP III) that is published by the National Institutes of Health – National Heart, Lung and Blood Institute. Major Classes of Drugs Available Affecting Lipoprotein Metabolism HMG CoA reductase inhibitors—lovastatin, pravastatin, simvastatin, fluvastatin, atorvastatin Bile acid sequestrants—cholestyramine, colestipol, colesevelam Nicotinic acid—crystalline, timed-release preparations, Niaspan® Fibric acid derivatives (fibrates)—gemfibrozil, fenofibrate, clofibrate Estrogen replacement Omega-3 fatty acids Major Uses and Lipid/ Lipoprotien Effects of Each Drug Class Drug Class Major Use Lipid/ Lipoprotein Effects LDL ↓ 18-55% HMG CoA reductase To lower LDL cholesterol HDL ↑ 5-15% inhibitors (statins) TG ↓ 7-30% LDL ↓ 15-30% Bile acid sequestrants To lower LDL cholesterol HDL ↑ 3-5% TG No effect or increase LDL ↓ 5-25% Useful in most lipid and Nicotinic acid HDL ↑ 15-35% lipoprotein abnormalities TG ↓ 20-50% LDL ↓ 5-20% (in nonhypertriglyceridemic persons); Hypertriglyceridemia; may be increased in hypertriglyceridemic persons Fibric acids Atherogenic dyslipidemia HDL ↑ 10-35% (more in severe hypertriglyceridemia) TG ↓ 20-50% NCEP Drug Treatment The information contained in this document is taken directly from the National Cholesterol Education Program, Adult Treatment Panel III (NCEP, ATP III) that is published by the National Institutes of Health – National Heart, Lung and
    [Show full text]
  • Lipid Lowering Drugs Prescription and the Risk of Peripheral Neuropathy
    1047 J Epidemiol Community Health: first published as 10.1136/jech.2003.013409 on 16 November 2004. Downloaded from RESEARCH REPORT Lipid lowering drugs prescription and the risk of peripheral neuropathy: an exploratory case-control study using automated databases Giovanni Corrao, Antonella Zambon, Lorenza Bertu`, Edoardo Botteri, Olivia Leoni, Paolo Contiero ............................................................................................................................... J Epidemiol Community Health 2004;58:1047–1051. doi: 10.1136/jech.2003.013409 Study objective: Although lipid lowering drugs are effective in preventing morbidity and mortality from cardiovascular events, the extent of their adverse effects is not clear. This study explored the association between prescription of lipid lowering drugs and the risk of peripheral neuropathy. Design: A population based case-control study was carried out by linkage of several automated databases. Setting: Resident population of a northern Italian Province aged 40 years or more. Participants: Cases were patients discharged for peripheral neuropathy in 1998–1999. For each case up See end of article for authors’ affiliations to 20 controls were randomly selected among those eligible. Altogether 2040 case patients and 36 041 ....................... controls were included in the study. Exposure ascertainment: Prescription drug database was used to assess exposure to lipid lowering drugs Correspondence to: Professor G Corrao, at any time in the one year period preceding the index date.
    [Show full text]
  • Anatomical Classification Guidelines V2020 EPHMRA ANATOMICAL
    EPHMRA ANATOMICAL CLASSIFICATION GUIDELINES 2020 Anatomical Classification Guidelines V2020 "The Anatomical Classification of Pharmaceutical Products has been developed and maintained by the European Pharmaceutical Marketing Research Association (EphMRA) and is therefore the intellectual property of this Association. EphMRA's Classification Committee prepares the guidelines for this classification system and takes care for new entries, changes and improvements in consultation with the product's manufacturer. The contents of the Anatomical Classification of Pharmaceutical Products remain the copyright to EphMRA. Permission for use need not be sought and no fee is required. We would appreciate, however, the acknowledgement of EphMRA Copyright in publications etc. Users of this classification system should keep in mind that Pharmaceutical markets can be segmented according to numerous criteria." © EphMRA 2020 Anatomical Classification Guidelines V2020 CONTENTS PAGE INTRODUCTION A ALIMENTARY TRACT AND METABOLISM 1 B BLOOD AND BLOOD FORMING ORGANS 28 C CARDIOVASCULAR SYSTEM 35 D DERMATOLOGICALS 50 G GENITO-URINARY SYSTEM AND SEX HORMONES 57 H SYSTEMIC HORMONAL PREPARATIONS (EXCLUDING SEX HORMONES) 65 J GENERAL ANTI-INFECTIVES SYSTEMIC 69 K HOSPITAL SOLUTIONS 84 L ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS 92 M MUSCULO-SKELETAL SYSTEM 102 N NERVOUS SYSTEM 107 P PARASITOLOGY 118 R RESPIRATORY SYSTEM 120 S SENSORY ORGANS 132 T DIAGNOSTIC AGENTS 139 V VARIOUS 141 Anatomical Classification Guidelines V2020 INTRODUCTION The Anatomical Classification was initiated in 1971 by EphMRA. It has been developed jointly by Intellus/PBIRG and EphMRA. It is a subjective method of grouping certain pharmaceutical products and does not represent any particular market, as would be the case with any other classification system.
    [Show full text]
  • Therapeutic Class Overview Fibric Acid Derivatives
    Therapeutic Class Overview Fibric Acid Derivatives Therapeutic Class • Overview/Summary: The fibric acid derivatives are agonists of the peroxisome proliferator activated receptor α (PPARα). Activation of PPARα increases lipolysis and elimination of triglyceride-rich particles from plasma by activating lipoprotein lipase and reducing production of apoprotein CIII. The resulting decrease in triglycerides (TG) produces an alteration in the size and composition of low- density lipoprotein cholesterol (LDL-C) from small, dense particles to large buoyant particles. There is also an increase in the synthesis of high-density lipoprotein cholesterol (HDL-C), as well as apoprotein AI and AII.1-10 The major action of this class of medications is to reduce TG. The fibric acid derivatives can decrease TG by 20 to 50% and increase HDL-C by 10 to 35%. They also lower LDL- C by 5 to 20%; however, in patients with hypertriglyceridemia, LDL-C may increase with the use of fibric acid derivatives.11 Several fenofibrate products are currently available, including micronized and non-micronized formulations. The different fenofibrate formulations are not equivalent on a milligram-to-milligram basis. Micronized fenofibrate is more readily absorbed than non-micronized formulations, which allows for a lower daily dose. Fenofibrate (micronized and non-micronized formulations), fenofibric acid, and gemfibrozil are available generically in at least one dosage form and/or strength.12 Fenofibrate and fenofibric acid are Food and Drug Administration (FDA)-approved for the treatment of hypercholesterolemia and mixed dyslipidemias, as well as hypertriglyceridemia. Gemfibrozil is FDA- approved for the treatment of hypertriglyceridemia and to reduce the risk of developing coronary heart disease (CHD) in select patients.13 Gemfibrozil has demonstrated a reduction in the risk of fatal and nonfatal myocardial infarction (MI) for primary prevention, as well as a reduction in CHD death and nonfatal MI and stroke for secondary prevention.
    [Show full text]
  • Phase 3 Evaluation of Bempedoic Acid Added to Ezetimibe in Patients with Elevated LDL‐ Cholesterol Receiving No Greater Than Low Dose Statins: CLEAR Tranquility
    Phase 3 Evaluation of Bempedoic Acid Added to Ezetimibe in Patients with Elevated LDL‐ Cholesterol Receiving No Greater Than Low Dose Statins: CLEAR Tranquility Christie M. Ballantyne, Baylor College of Medicine, Houston, United States of America Maciej Banach, Medical University of Lodz, Lodz, Poland G.B. John Mancini, University of British Columbia, Vancouver, Canada Norman E. Lepor, Westside Medical Associates of Los Angeles, Beverly Hills, United States of America Jeffrey C. Hanselman, Esperion Therapeutics Inc., Ann Arbor, United States of America Xin Zhao, Esperion Therapeutics Inc., Ann Arbor, United States of America Lawrence A. Leiter, Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto, Canada XVIIIth International Symposium on Atherosclerosis June 12, 2018 Oral Presentation Disclosures for Christie M. Ballantyne Grant/Research Support (all paid to institution, not individual): Abbott Diagnostic, Akcea, Amarin, Amgen, Esperion, Novartis, Regeneron, Roche Diagnostic, Sanofi‐Synthelabo, NIH, ADA, AHA Consultant: Abbott Diagnostics, Akcea, Amarin, Amgen, Astra Zeneca, Boehringer Ingelheim, Denka Seiken, Eli Lilly, Esperion, Matinas BioPharma Inc, Merck, Novartis, Novo Nordisk, Regeneron, Roche Diagnostic, Sanofi‐Synthelabo Bempedoic Acid Overview Pharmacologic properties and Mechanism of action • Oral, once‐daily tablet • MOA: First‐in class inhibitor of ATP‐citrate lyase (ACL) • Shown in phase 2 studies to lower LDL‐C: • as monotherapy • in combination with ezetimibe, statins and PCSK9 inhibitors
    [Show full text]