DOCSLIB.ORG

Anacetrapib for the Treatment of Dyslipidemia

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Anacetrapib for the Treatment of Dyslipidemia Issues in Emerging Health Technologies Anacetrapib for the Treatment of Dyslipidemia Issue 123 February 2013 [DRAFT] Summary Background Anacetrapib (Merck & Co., Inc) is a cholesterol Cardiovascular disease is one of the leading causes of ester transfer protein (CETP) inhibitor that morbidity and mortality in Canada.1,2 In 2009, almost blocks the transfer of cholesterol from high- 30% of all deaths in Canada were the result of density lipoprotein to other lipoproteins. This cardiovascular disease.2 The economic burden of results in an increase in high-density lipoprotein cholesterol (HDL-C) and a decrease in low- cardiovascular disease in Canada is substantial. The density lipoprotein cholesterol (LDL-C), which total cost for the use of health care resources and lost may reduce the development of atherosclerosis. productivity was estimated to be C$20.9 billion in Anacetrapib has not been approved for sale in 2005.3 This figure is expected to increase to Canada or the United States. C$28.3 billion in 2020.3 Statin therapy has been shown Clinical evidence to support the use of to decrease LDL-C by approximately 25% to 50%, with anacetrapib for dyslipidemia has been reported a corresponding 24% to 40% risk reduction in in two clinical trials. An eight-week phase 2b cardiovascular events.4 However, many patients remain dose-ranging study in patients with primary at risk for future cardiovascular events despite treatment hypercholesterolemia or mixed hyperlipidemia with statins.5-8 This may be explained by a low level of reported statistically significant increases in HDL-C, which has been shown to be a significant HDL-C of up to 139% and statistically predictor of coronary artery disease.9,10 Epidemiologic significant reductions in LDL-C of up to 40% compared with placebo. The DEFINE data have shown that the cardiovascular benefit from phase 3 clinical trial showed that, when used higher HDL-C levels is independent of the benefit 11-14 concomitantly with a statin in patients with associated with lower LDL-C levels. This suggests known coronary artery disease or who were at that strategies that increase HDL-C, when added to high-risk for coronary artery disease, those that lower LDL-C, may reduce cardiovascular risk anacetrapib produced a 39.8% reduction in more so than approaches that focus only on decreasing LDL-C and a 138.1% increase in HDL-C at LDL-C. 24 weeks compared with placebo. These lipid changes were sustained at 76 weeks. The Technology Adverse effects were mostly mild to moderate, and consisted of gastrointestinal symptoms Anacetrapib (Merck & Co. Inc., Whitehouse Station, (diarrhea, constipation, dyspepsia) and myalgias. New Jersey) is an orally active cholesterol ester transfer There was no evidence of effects on blood protein (CETP) inhibitor.15 CETP is a plasma protein pressure, serum levels of aldosterone, serum that facilitates the transfer of cholesterol and levels of electrolytes, or an increased risk of 16 cardiovascular events. triglycerides between various lipoprotein fractions. HDL particles play a central role in reverse cholesterol REVEAL is an ongoing, large-scale phase 3 trial transport, a process that removes excess cholesterol evaluating the effectiveness of anacetrapib with a from peripheral tissues and transports it to the liver for statin for the secondary prevention of major coronary events in patients who have a history of excretion. Pharmacologic inhibition of CETP blocks the cardiovascular disease. Results are anticipated in transfer of cholesterol from HDL to other lipoproteins January 2017. such as LDL and very low-density lipoprotein (VLDL). The result is an accumulation of cholesterol in the HDL The long-term safety and efficacy of anacetrapib for the primary or secondary prevention of fraction, which may reduce the development of cardiovascular morbidity and mortality needs to atherosclerosis (a narrowing of arteries due to an be clarified to determine the impact on clinical accumulation of fatty deposits or plaques in the practice. arterial wall). The Canadian Agency for Drugs and Technologies in Health (CADTH) is funded by Canadian federal, provincial, and territorial governments. (www.cadth.ca) The development of the previous investigational CETP dyslipidemia should be based on the risk of coronary inhibitors torcetrapib (Pfizer Inc., New York, New artery disease and lipid levels.25 Cardiovascular risk is York) and dalcetrapib (Roche, Basel, Switzerland) was estimated using the Framingham Risk Score based on discontinued. Despite a 72% increase in HDL-C and a the patient’s age, sex, and presence of comorbidities 25% decrease in LDL-C, development of torcetrapib such as diabetes, hypertension, familial hyperlipidemia, was stopped in 2006 after results from a pivotal trial family history of premature cardiovascular disease, and showed that torcetrapib was associated with an clinical evidence of atherosclerotic cardiovascular increased risk of cardiovascular events and mortality.17 disease. Treatment is considered in all high-risk patients These adverse events may have been the result of “off even if cholesterol levels are normal. Treatment is also target” effects on serum electrolyte levels, serum considered in moderate-risk or low-risk patients aldosterone levels, blood pressure, and prolongation of depending on the levels of LDL-C, apolipoprotein B the QT interval on electrocardiogram readings that (apo B), and non-HDL-C. The guidelines recommend were unrelated to CETP inhibition.18,19 Furthermore, LDL-C reduction with statins (e.g., simvastatin, three studies failed to show any effect on atorvastatin) as the primary target of therapy. The goal atherosclerotic plaque progression.20-22 Dalcetrapib of treatment is an LDL-C level of 2.0 mmol/L was a relatively weak CETP inhibitor that produced a (77.3 mg/dL) or less, or a 50% or greater reduction in 30% increase in HDL-C and did not significantly the LDL-C level. Alternate targets include a reduction in affect LDL-C.23 The development of dalcetrapib was apo B or non-HDL-C levels. terminated early in 2012 when a phase 3 trial in The goals of treating patients with low HDL-C levels patients with stable coronary artery disease failed to have not been established due to the absence of evidence show clinically meaningful efficacy when added to a showing an improvement in cardiovascular outcomes statin for a reduction in cardiovascular events.23,24 with therapies that increase HDL-C alone. Niacin is currently the most effective drug for increasing HDL-C, Regulatory Status but use is limited by adverse effects including skin flushing and liver toxicity. Fibrates (e.g., gemfibrozil) Anacetrapib is not currently approved for sale in have also been shown to increase HDL-C, but are Canada or the United States. associated with muscle toxicity when used with a statin. Furthermore, several clinical trials have suggested that Patient Group adding extended-release niacin27,28 or fibrates29 to a Dyslipidemia (an abnormal level of lipids and statin does not decrease the risk of cardiovascular events lipoproteins in the blood) is a major risk factor for relative to statin monotherapy. developing cardiovascular disease.1,25 Higher concentrations of LDL-C and lower concentrations of Methods HDL-C increase the risk for atherosclerosis.26 Progression of atherosclerosis may lead to coronary Literature Search Strategy A peer-reviewed literature search was conducted using artery disease, myocardial infarction, heart failure, the following bibliographic databases: MEDLINE, peripheral artery disease, and stroke. A substantial PubMed, Embase, and The Cochrane Library (2012, proportion of Canadians aged 20 to 79 years are Issue 12). Grey literature was identified by searching estimated to have a high level of LDL-C (36%) and a 26 relevant sections of the Grey Matters checklist low level of HDL-C (30%). An LDL-C level of (http://www.cadth.ca/en/resources/grey-matters). No 5.0 mmol/L (193.3 mg/dL) or greater is considered 25 methodological filters were applied. The search was high for most patients. An LDL-C level of limited to English language documents published 3.5 mmol/L (135.3 mg/dL) or greater is considered between January 1, 2007 and December 11, 2012. high for patients who are at increased risk of 25 Regular alerts were established to update the search cardiovascular disease. A low HDL-C level is less until the publication of the bulletin. Conference than 1.0 mmol/L (38.7 mg/dL) in men and less than 26 abstracts were excluded from the search results. 1.3 mmol/L (50.3 mg/dl) in women. Study Selection Criteria Current Practice Phase 2 and 3 studies evaluating the efficacy and safety Guidelines from the Canadian Cardiovascular Society of anacetrapib compared with placebo or pharmacologic recommend that the initiation of treatment for therapies for the treatment of dyslipidemia and cardiovascular disease were considered for inclusion in The Canadian Agency for Drugs and Technologies in Health (CADTH) is funded by Canadian federal, provincial, and territorial governments. (www.cadth.ca) the evidence section of this bulletin. Unpublished data, The baseline demographic and clinical characteristics case reports, editorials, letters, and narrative literature were similar across the 10 treatment groups. The mean reviews were excluded. age was 56.4 9.6 years and the majority (83.7%) of participants were Caucasian. The mean baseline levels The Evidence for LDL-C and apo B were 141.1 22.0 mg/dL and 142.5 23.8 mg/dL, respectively. The mean baseline Clinical data to support the use of anacetrapib in levels for HDL-C and apo A-I were 50.5 12.6 mg/dL dyslipidemia and coronary artery disease have been and 168.9 27.7 mg/dL, respectively. Overall, reported in a phase 2b dose-ranging study30,31 and a 32 26 (4.0%) patients had diabetes and 223 (37.9%) had phase 3 clinical trial.
Load more

Recommended publications
  • Prevention of Coronary Heart Disease
    PREVENTION OF CORONARY PATIENT WITH CHD HEART DISEASE • Obese male patient with previous angina, cardiac catheterization with placement of two stents and now stable. • Notable clinical characteristics: Thomas F . Wh ayne, J r, MD , PhD, FACC Triglycerides 354 mg/dl. Professor of Medicine (Cardiology) HDL 28 mg/dl in men. Gill Heart Institute BP 140/90 mm/Hg. University of Kentucky Fasting glucose 120 mg/dl. November, 2009 • Specific management? Characteristics of Plaques Prone to HIGH SENSENSITIVITY Rupture From Inflammation and LDL CREACTIVE PROTEIN (hs-CRP) Fibrous cap Media • A MARKER OF INFLAMMATION: CRP AND Lumen Lipid hsCRP ARE SAME PROTEIN Core • MAY BE ANOTHER RISK FACTOR AND PLAY A ROLE IN PLAQUE FORMATION “Vulnerable” plaque • MAY PREDICT HIGH RISK ACUTE CORONARY SYNDROME • MAY INDICATE PATIENTS MOST LIKELY TO Lumen RESPOND TO STATINS T lymphocyte Lipid • STATINS SHOWN TO REDUCE CRP Core Macrophage foam cell (tissue factor) “Activated” Intimal SMC (HLA-DR+) – EZETIMIBE ACCENTUATES THIS EFFECT* “Stable” plaque Normal medial SMC • NEED STATIN DOSE RESPONSE CURVE Libby P. Circulation. 1999; 91:284491:2844--2850.2850. *Sager PT, et al. Am J Cardiol. 2003;92:1414-1418. Resultados Estudio VYTAL sobre PCR: Ezetimiba/Simvastatina vs. Atorvastatina en pts con DM II e Hipercolesterolemia (n=1229) CURRENT CLINICALLY USEFUL MARKERS OF INFLAMMATION Atorvastatina E/Simvas Atorvas E/S 10 mg 20 mg 10/20 40 mg 10/40 0 • LIPOPROTEIN-ASSOCIATED Ezetimiba/ --55 Simvastatina PHOSPHOLIPASE A2*. Atorvastatina ® asales --1010 a Sensibilidad – PLAC TEST. t b --1515 --13.713.7 de Al --13.813.8 • HIGH SENSITIVITY C-REACTIVE --2020 # PCR PROTEIN (hsCRP) .
    [Show full text]
  • 1 CETP Inhibition Improves HDL Function but Leads to Fatty Liver and Insulin Resistance in CETP-Expressing Transgenic Mice on A
    Page 1 of 55 Diabetes CETP inhibition improves HDL function but leads to fatty liver and insulin resistance in CETP-expressing transgenic mice on a high-fat diet Lin Zhu1,2, Thao Luu2, Christopher H. Emfinger1,2, Bryan A Parks5, Jeanne Shi2,7, Elijah Trefts3, Fenghua Zeng4, Zsuzsanna Kuklenyik5, Raymond C. Harris4, David H. Wasserman3, Sergio Fazio6 and John M. Stafford1,2,3,* 1VA Tennessee Valley Healthcare System, 2Division of Diabetes, Endocrinology, & Metabolism, 3Department of Molecular Physiology and Biophysics, 4Devision of Nephrology and Hypertension, Vanderbilt University School of Medicine. 5Division of Laboratory Sciences, Centers for Disease Control and Prevention. 6The Center for Preventive Cardiology at the Knight Cardiovascular Institute, Oregon Health & Science University. 7Trinity College of Art and Science, Duke University. * Address correspondence and request for reprints to: John. M. Stafford, 7445D Medical Research Building IV, Nashville, TN 37232-0475, phone (615) 936-6113, fax (615) 936- 1667 Email: [email protected] Running Title: CETP inhibition and insulin resistance Word Count: 5439 Figures: 7 Tables: 1 1 Diabetes Publish Ahead of Print, published online September 13, 2018 Diabetes Page 2 of 55 Abstract In clinical trials inhibition of cholesteryl ester transfer protein (CETP) raises HDL cholesterol levels but doesn’t robustly improve cardiovascular outcomes. About 2/3 of trial participants were obese. Lower plasma CETP activity is associated with increased cardiovascular risk in human studies, and protective aspects of CETP have been observed in mice fed a high-fat diet (HFD) with regard to metabolic outcomes. To define if CETP inhibition has different effects depending on the presence of obesity, we performed short- term anacetrapib treatment in chow- and HFD-fed CETP-transgenic mice.
    [Show full text]
  • PHARMACEUTICAL APPENDIX to the TARIFF SCHEDULE 2 Table 1
    Harmonized Tariff Schedule of the United States (2020) Revision 19 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2020) Revision 19 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 2 Table 1. This table enumerates products described by International Non-proprietary Names INN which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service CAS registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known.
    [Show full text]
  • Dysfunctional High-Density Lipoproteins in Type 2 Diabetes Mellitus: Molecular Mechanisms and Therapeutic Implications
    Journal of Clinical Medicine Review Dysfunctional High-Density Lipoproteins in Type 2 Diabetes Mellitus: Molecular Mechanisms and Therapeutic Implications Isabella Bonilha 1 , Francesca Zimetti 2,* , Ilaria Zanotti 2 , Bianca Papotti 2 and Andrei C. Sposito 1,* 1 Atherosclerosis and Vascular Biology Laboratory (AtheroLab), Cardiology Department, State University of Campinas (Unicamp), Campinas 13084-971, Brazil; [email protected] 2 Department of Food and Drug, University of Parma, 43124 Parma, Italy; [email protected] (I.Z.); [email protected] (B.P.) * Correspondence: [email protected] (F.Z.); [email protected] (A.C.S.); Tel.: +39-05-2190-6172 (F.Z.); +55-19-3521-7098 (A.C.S.); Fax: +55-1-9328-9410 (A.C.S.) Abstract: High density lipoproteins (HDLs) are commonly known for their anti-atherogenic prop- erties that include functions such as the promotion of cholesterol efflux and reverse cholesterol transport, as well as antioxidant and anti-inflammatory activities. However, because of some chronic inflammatory diseases, such as type 2 diabetes mellitus (T2DM), significant changes occur in HDLs in terms of both structure and composition. These alterations lead to the loss of HDLs’ physiological functions, to transformation into dysfunctional lipoproteins, and to increased risk of cardiovascular disease (CVD). In this review, we describe the main HDL structural/functional alterations observed in T2DM and the molecular mechanisms involved in these T2DM-derived modifications. Finally, the main available therapeutic interventions targeting HDL in diabetes are discussed. Citation: Bonilha, I.; Zimetti, F.; Keywords: high density lipoprotein; type 2 diabetes mellitus; HDL function; glycation; oxidation; Zanotti, I.; Papotti, B.; Sposito, A.C.
    [Show full text]
  • Patent Application Publication ( 10 ) Pub . No . : US 2019 / 0192440 A1
    US 20190192440A1 (19 ) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2019 /0192440 A1 LI (43 ) Pub . Date : Jun . 27 , 2019 ( 54 ) ORAL DRUG DOSAGE FORM COMPRISING Publication Classification DRUG IN THE FORM OF NANOPARTICLES (51 ) Int . CI. A61K 9 / 20 (2006 .01 ) ( 71 ) Applicant: Triastek , Inc. , Nanjing ( CN ) A61K 9 /00 ( 2006 . 01) A61K 31/ 192 ( 2006 .01 ) (72 ) Inventor : Xiaoling LI , Dublin , CA (US ) A61K 9 / 24 ( 2006 .01 ) ( 52 ) U . S . CI. ( 21 ) Appl. No. : 16 /289 ,499 CPC . .. .. A61K 9 /2031 (2013 . 01 ) ; A61K 9 /0065 ( 22 ) Filed : Feb . 28 , 2019 (2013 .01 ) ; A61K 9 / 209 ( 2013 .01 ) ; A61K 9 /2027 ( 2013 .01 ) ; A61K 31/ 192 ( 2013. 01 ) ; Related U . S . Application Data A61K 9 /2072 ( 2013 .01 ) (63 ) Continuation of application No. 16 /028 ,305 , filed on Jul. 5 , 2018 , now Pat . No . 10 , 258 ,575 , which is a (57 ) ABSTRACT continuation of application No . 15 / 173 ,596 , filed on The present disclosure provides a stable solid pharmaceuti Jun . 3 , 2016 . cal dosage form for oral administration . The dosage form (60 ) Provisional application No . 62 /313 ,092 , filed on Mar. includes a substrate that forms at least one compartment and 24 , 2016 , provisional application No . 62 / 296 , 087 , a drug content loaded into the compartment. The dosage filed on Feb . 17 , 2016 , provisional application No . form is so designed that the active pharmaceutical ingredient 62 / 170, 645 , filed on Jun . 3 , 2015 . of the drug content is released in a controlled manner. Patent Application Publication Jun . 27 , 2019 Sheet 1 of 20 US 2019 /0192440 A1 FIG .
    [Show full text]
  • Pharmacogenomics Variability of Lipid-Lowering Therapies in Familial Hypercholesterolemia
    Journal of Personalized Medicine Review Pharmacogenomics Variability of Lipid-Lowering Therapies in Familial Hypercholesterolemia Nagham N. Hindi 1,†, Jamil Alenbawi 1,† and Georges Nemer 1,2,* 1 Division of Genomics and Translational Biomedicine, College of Health and Life Sciences, Hamad Bin Khalifa University, Doha P.O. Box 34110, Qatar; [email protected] (N.N.H.); [email protected] (J.A.) 2 Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut DTS-434, Lebanon * Correspondence: [email protected]; Tel.: +974-445-41330 † Those authors contributed equally to the work. Abstract: The exponential expansion of genomic data coupled with the lack of appropriate clinical categorization of the variants is posing a major challenge to conventional medications for many common and rare diseases. To narrow this gap and achieve the goals of personalized medicine, a collaborative effort should be made to characterize the genomic variants functionally and clinically with a massive global genomic sequencing of “healthy” subjects from several ethnicities. Familial- based clustered diseases with homogenous genetic backgrounds are amongst the most beneficial tools to help address this challenge. This review will discuss the diagnosis, management, and clinical monitoring of familial hypercholesterolemia patients from a wide angle to cover both the genetic mutations underlying the phenotype, and the pharmacogenomic traits unveiled by the conventional and novel therapeutic approaches. Achieving a drug-related interactive genomic map will potentially benefit populations at risk across the globe who suffer from dyslipidemia. Citation: Hindi, N.N.; Alenbawi, J.; Nemer, G. Pharmacogenomics Variability of Lipid-Lowering Keywords: familial hypercholesterolemia; pharmacogenomics; PCSK9 inhibitors; statins; ezetimibe; Therapies in Familial novel lipid-lowering therapy Hypercholesterolemia.
    [Show full text]
  • Pharmacological Targeting of the Atherogenic Dyslipidemia Complex: the Next Frontier in CVD Prevention Beyond Lowering LDL Cholesterol
    Diabetes Volume 65, July 2016 1767 Changting Xiao,1 Satya Dash,1 Cecilia Morgantini,1 Robert A. Hegele,2 and Gary F. Lewis1 Pharmacological Targeting of the Atherogenic Dyslipidemia Complex: The Next Frontier in CVD Prevention Beyond Lowering LDL Cholesterol Diabetes 2016;65:1767–1778 | DOI: 10.2337/db16-0046 Notwithstanding the effectiveness of lowering LDL cho- has been the primary goal of dyslipidemia management, lesterol, residual CVD risk remains in high-risk popula- with statins as the treatment of choice for CVD prevention. tions, including patients with diabetes, likely contributed Large-scale, randomized, clinical trials of LDL-lowering PERSPECTIVES IN DIABETES to by non-LDL lipid abnormalities. In this Perspectives therapies have demonstrated significant reduction in CVD in Diabetes article, we emphasize that changing demo- events over a wide range of baseline LDL-C levels (2,3). graphics and lifestyles over the past few decades have However, even with LDL-C levels lowered substantially or “ resulted in an epidemic of the atherogenic dyslipidemia at treatment goals with statin therapy, CVD risks are not ” complex, the main features of which include hypertrigly- eliminated and there remains significant “residual risk.” In- ceridemia, low HDL cholesterol levels, qualitative changes tensifying statin therapy may provide additional benefits in LDL particles, accumulation of remnant lipoproteins, (4,5); this approach, however, has limited potential, owing and postprandial hyperlipidemia. We brieflyreviewthe to tolerability, side effects, and finite efficacy. Further LDL-C underlying pathophysiology of this form of dyslipidemia, lowering may also be achieved with the use of nonstatin in particular its association with insulin resistance, obe- sity, and type 2 diabetes, and the marked atherogenicity agents, such as cholesterol absorption inhibitors and PCSK9 of this condition.
    [Show full text]
  • I Regulations
    23.2.2007 EN Official Journal of the European Union L 56/1 I (Acts adopted under the EC Treaty/Euratom Treaty whose publication is obligatory) REGULATIONS COUNCIL REGULATION (EC) No 129/2007 of 12 February 2007 providing for duty-free treatment for specified pharmaceutical active ingredients bearing an ‘international non-proprietary name’ (INN) from the World Health Organisation and specified products used for the manufacture of finished pharmaceuticals and amending Annex I to Regulation (EEC) No 2658/87 THE COUNCIL OF THE EUROPEAN UNION, (4) In the course of three such reviews it was concluded that a certain number of additional INNs and intermediates used for production and manufacture of finished pharmaceu- ticals should be granted duty-free treatment, that certain of Having regard to the Treaty establishing the European Commu- these intermediates should be transferred to the list of INNs, nity, and in particular Article 133 thereof, and that the list of specified prefixes and suffixes for salts, esters or hydrates of INNs should be expanded. Having regard to the proposal from the Commission, (5) Council Regulation (EEC) No 2658/87 of 23 July 1987 on the tariff and statistical nomenclature and on the Common Customs Tariff (1) established the Combined Nomenclature Whereas: (CN) and set out the conventional duty rates of the Common Customs Tariff. (1) In the course of the Uruguay Round negotiations, the Community and a number of countries agreed that duty- (6) Regulation (EEC) No 2658/87 should therefore be amended free treatment should be granted to pharmaceutical accordingly, products falling within the Harmonised System (HS) Chapter 30 and HS headings 2936, 2937, 2939 and 2941 as well as to designated pharmaceutical active HAS ADOPTED THIS REGULATION: ingredients bearing an ‘international non-proprietary name’ (INN) from the World Health Organisation, specified salts, esters or hydrates of such INNs, and designated inter- Article 1 mediates used for the production and manufacture of finished products.
    [Show full text]
  • Effect of Evacetrapib on Cardiovascular Outcomes in Patients with High-Risk Cardiovascular Disease
    Touro Scholar NYMC Faculty Publications Faculty 7-1-2017 Effect of Evacetrapib on Cardiovascular Outcomes in Patients with High-risk Cardiovascular Disease Wilbert S. Aronow New York Medical College Follow this and additional works at: https://touroscholar.touro.edu/nymc_fac_pubs Part of the Cardiology Commons, and the Cardiovascular Diseases Commons Recommended Citation Aronow, W. S. (2017). Effect of Evacetrapib on Cardiovascular Outcomes in Patients with High-risk Cardiovascular Disease. Journal of Thoracic Disease, 9 (7), 1822-1825. https://doi.org/10.21037/ jtd.2017.06.106 This Editorial is brought to you for free and open access by the Faculty at Touro Scholar. It has been accepted for inclusion in NYMC Faculty Publications by an authorized administrator of Touro Scholar. For more information, please contact [email protected]. 1825 Editorial Effect of evacetrapib on cardiovascular outcomes in patients with high-risk cardiovascular disease Wilbert S. Aronow Department of Medicine, Division of Cardiology, Westchester Medical Center and New York Medical College, Valhalla, NY, USA Correspondence to: Wilbert S. Aronow, MD, FACC, FAHA. Professor of Medicine, Cardiology Division, Westchester Medical Center and New York Medical College, Macy Pavilion, Room 141, Valhalla, NY 10595, USA. Email: [email protected]. Provenance: This is an invited Editorial commissioned by Section Editor Dr. Hai-Long Dai (Department of Cardiology, Yan'an Affiliated Hospital of Kunming Medical University, Kunming, China). Comment on: Lincoff AM, Nicholls SJ, Riesmeyer JS, et al. Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease. N Engl J Med 2017;376:1933-42. Submitted Jun 12, 2017. Accepted for publication Jun 13, 2017.
    [Show full text]
  • Statin + Ezetimibe : ENHANCE, SHARP • Statin + Niacin : AIM-HIGH, HPS2-THRIVE • Statin + Fenofibrate : ACCORD Lipid Stain Vs
    Need for Additional Emerging Targets? Ultimate Goal for Lipid Management Bum-Kee Hong Cardiology Heart Center Yonsei Universityyg College of Medicine Seoul, Korea As you know , there are many concrete beneficial evidences of LDL -lowering statin therapy!!! LDL-C Lowering & Benefit of Statins CTT Meta-Analysis CTT 2005 1 CTT 2010 2 CTT 2012 3 Number of analyzed trials 14 (90,056) 26 (169,138) 27 (174,149) (Number of patients) More vs. Less intensive statin Statin vs. Comparison Statin vs. Control Stain/More vs. Control/Less Control Stain/More vs. Control/Less Classified based on 5-year major vascular event (MVE) risk at No No Yes baseline More vs. Less intensive statin: 28% Data according to 5-year MVE Reduction of MVE risk 21% Statin vs. Control: 21% risk per 1 mmol/L reduction of LDL-C* *LDL-C: 1 mmol/L=38.61mg/dL Stain/More vs. Control/Less: 1.(Next Lancet page) 2005;366:1267-78 22% 2. Lancet 2010;376:1670-81 3. Lancet 2010;380:581-90 CTT Meta-Analysis from CTT 2012 MVE at Difference Risk Levels However, there is still CV risk despite the use of aggressive statin therapy... What Is Residual Cardiovascular Risk? Statin trials show many patients at LDL-C goal have high “idl”“residual” CHD rikisk1. Statins reduce risk by about 30% compared with controls, but many patients still have events due to residual risk2-4. More intensive treatment directed to other targets as well as LDL-C is needed in addition to statin monotherapy to reduce residual risk effectively.
    [Show full text]
  • Articles Article: Non-Statin Treatments for Managing LDL Cholesterol and Their Outcomes Download
    Clinical Therapeutics/Volume 37, Number 12, 2015 Review Article Non-statin Treatments for Managing LDL Cholesterol and Their Outcomes Traci Turner, MD; and Evan A. Stein, MD, PhD Metabolic & Atherosclerosis Research Center, Cincinnati, Ohio ABSTRACT agents are being developed as orphan indications ex- Purpose: Over the past 3 decades reducing LDL-C pressly for patients with homozygous familial hyper- has proven to be the most reliable and easily achiev- cholesterolemia, including peroxisome proliferator able modifiable risk factor to decrease the rate of activated receptor-δ agonists, angiopoietin-like protein 3 cardiovascular morbidity and mortality. Statins are inhibitors, and gene therapy. effective, but problems with their side effects, adher- Implications: Monoclonal antibodies that inhibit ence, or LDL-C efficacy in some patient groups PCSK9 were shown to be very effective reducers of remain. Most currently available alternative lipid- LDL-C and well tolerated despite subcutaneous ad- modifying therapies have limited efficacy or tolerabil- ministration, and no significant safety issues have yet ity, and additional effective pharmacologic modalities emerged during large Phase II and III trials. They have to reduce LDL-C are needed. the potential to substantially impact further the risk of Methods: Recent literature on new and evolving cardiovascular disease. A number of additional new, LDL-C–lowering modalities in preclinical and clinical but less effective, oral LDL-C–lowering agents are development was reviewed. also in various stages of development, including Findings: Several new therapies targeting LDL-C are some which are targeted only to patients with homo- in development. Inhibition of proprotein convertase sub- zygous familial hypercholesterolemia. (Clin Ther.
    [Show full text]
  • 2 12/ 35 74Al
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date 22 March 2012 (22.03.2012) 2 12/ 35 74 Al (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 9/16 (2006.01) A61K 9/51 (2006.01) kind of national protection available): AE, AG, AL, AM, A61K 9/14 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, (21) International Application Number: DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/EP201 1/065959 HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, (22) International Filing Date: KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, 14 September 201 1 (14.09.201 1) ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, QA, RO, RS, RU, (25) Filing Language: English RW, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, (26) Publication Language: English TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: 61/382,653 14 September 2010 (14.09.2010) US (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (71) Applicant (for all designated States except US): GM, KE, LR, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, NANOLOGICA AB [SE/SE]; P.O Box 8182, S-104 20 ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, Stockholm (SE).
    [Show full text]