Nonstatin Therapies for Management of Dyslipidemia: A Review
Abstract Purpose Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States. Recently published cholesterol treatment guidelines emphasize the use of statins as the preferred treatment strategy for both primary and secondary prevention of CVD. However, the opti...
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| Veröffentlicht in: | Clinical therapeutics 2015-10, Vol.37 (10), p.2153-2179 |
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| description | Abstract Purpose Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States. Recently published cholesterol treatment guidelines emphasize the use of statins as the preferred treatment strategy for both primary and secondary prevention of CVD. However, the optimal treatment strategy for patients who cannot tolerate statin therapy or those who need additional lipid-lowering therapy is unclear in light of recent evidence that demonstrates a lack of improved cardiovascular outcomes with combination therapy. The purpose of this review is to summarize and interpret evidence that evaluates nonstatin drug classes in reducing cardiovascular outcomes, to provide recommendations for use of nonstatin therapies in clinical practice, and to review emerging nonstatin therapies for management of dyslipidemia. Methods Relevant articles were identified through searches of PubMed, International Pharmaceutical Abstracts, and the Cochrane Database of Systematic Reviews by using the terms niacin, omega-3 fatty acids (FAs), clofibrate, fibrate, fenofibrate, fenofibric acid, gemfibrozil, cholestyramine, colestipol, colesevelam, ezetimibe, proprotein convertase subtilisin/kexin 9 (PCSK9), cholesteryl ester transfer protein (CETP), and cardiovascular outcomes. Only English language, human clinical trials, meta-analyses, and systematic reviews were included. Additional references were identified from citations of published articles. Findings Niacin may reduce cardiovascular events as monotherapy; however, recent trials in combination with statins have failed to show a benefit. Trials with omega-3 FAs have failed to demonstrate significant reductions in cardiovascular outcomes. Fibrates may improve cardiovascular outcomes as monotherapy; however, trials in combination with statins have failed to show a benefit, except in those with elevated triglycerides (>200 mg/dL) or low HDL-C ( |
| doi_str_mv | 10.1016/j.clinthera.2015.09.001 |
| format | Article |
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Recently published cholesterol treatment guidelines emphasize the use of statins as the preferred treatment strategy for both primary and secondary prevention of CVD. However, the optimal treatment strategy for patients who cannot tolerate statin therapy or those who need additional lipid-lowering therapy is unclear in light of recent evidence that demonstrates a lack of improved cardiovascular outcomes with combination therapy. The purpose of this review is to summarize and interpret evidence that evaluates nonstatin drug classes in reducing cardiovascular outcomes, to provide recommendations for use of nonstatin therapies in clinical practice, and to review emerging nonstatin therapies for management of dyslipidemia. Methods Relevant articles were identified through searches of PubMed, International Pharmaceutical Abstracts, and the Cochrane Database of Systematic Reviews by using the terms niacin, omega-3 fatty acids (FAs), clofibrate, fibrate, fenofibrate, fenofibric acid, gemfibrozil, cholestyramine, colestipol, colesevelam, ezetimibe, proprotein convertase subtilisin/kexin 9 (PCSK9), cholesteryl ester transfer protein (CETP), and cardiovascular outcomes. Only English language, human clinical trials, meta-analyses, and systematic reviews were included. Additional references were identified from citations of published articles. Findings Niacin may reduce cardiovascular events as monotherapy; however, recent trials in combination with statins have failed to show a benefit. Trials with omega-3 FAs have failed to demonstrate significant reductions in cardiovascular outcomes. Fibrates may improve cardiovascular outcomes as monotherapy; however, trials in combination with statins have failed to show a benefit, except in those with elevated triglycerides (>200 mg/dL) or low HDL-C (<40 mg/dL). There is a lack of data that evaluates bile acid sequestrant in combination with statin therapy on reducing cardiovascular events. Ezetimibe–statin combination therapy can reduce cardiovascular outcomes in those with chronic kidney disease and following vascular surgery or acute coronary syndrome. Long-term effects of emerging nonstatin therapies (CETP and PCSK9 inhibitors) are currently being evaluated in ongoing Phase III trials. Implications Nonstatin therapies have a limited role in reducing cardiovascular events in those maintained on guideline-directed statin therapy. In certain clinical situations, such as patients who are unable to tolerate statin therapy or recommended intensities of statin therapy, those with persistent severe elevations in triglycerides, or patients with high cardiovascular risk, some nonstatin therapies may be useful in reducing cardiovascular events. Future research is needed to evaluate the role of nonstatin therapies in those who are unable to tolerate guideline-directed statin doses.</description><identifier>ISSN: 0149-2918</identifier><identifier>EISSN: 1879-114X</identifier><identifier>DOI: 10.1016/j.clinthera.2015.09.001</identifier><identifier>PMID: 26412799</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Anticholesteremic Agents - therapeutic use ; bile acid sequestrant ; Cardiovascular disease ; Cardiovascular Diseases - prevention & control ; Cholesterol ; Cholesterol Ester Transfer Proteins - therapeutic use ; Cholesterol, LDL - blood ; Clinical trials ; Clofibrate - therapeutic use ; Disease Management ; Dyslipidemias - drug therapy ; ezetimibe ; Ezetimibe - therapeutic use ; Fatty Acids, Omega-3 - therapeutic use ; fenofibrate ; Heart attacks ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use ; Internal Medicine ; Medical Education ; Mortality ; niacin ; Niacin - therapeutic use ; non-statin therapy ; omega-3 fatty acid ; Proprotein Convertases - metabolism ; Proprotein Convertases - therapeutic use ; Risk Factors ; Saccharomyces cerevisiae Proteins - therapeutic use ; Statins ; Triglycerides - blood ; United States</subject><ispartof>Clinical therapeutics, 2015-10, Vol.37 (10), p.2153-2179</ispartof><rights>Elsevier HS Journals, Inc.</rights><rights>2015 Elsevier HS Journals, Inc.</rights><rights>Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.</rights><rights>Copyright Elsevier Limited Oct 2015</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c520t-7f5ab0bd2bcb58a8cbe3600ac87a4b1cc3220610a22e78c4431a3d6e7dd5a7e03</citedby><cites>FETCH-LOGICAL-c520t-7f5ab0bd2bcb58a8cbe3600ac87a4b1cc3220610a22e78c4431a3d6e7dd5a7e03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/1725682992?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,780,784,3548,27923,27924,45994,64384,64386,64388,72240</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26412799$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sando, Karen R., PharmD</creatorcontrib><creatorcontrib>Knight, Michelle, PharmD</creatorcontrib><title>Nonstatin Therapies for Management of Dyslipidemia: A Review</title><title>Clinical therapeutics</title><addtitle>Clin Ther</addtitle><description>Abstract Purpose Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States. Recently published cholesterol treatment guidelines emphasize the use of statins as the preferred treatment strategy for both primary and secondary prevention of CVD. However, the optimal treatment strategy for patients who cannot tolerate statin therapy or those who need additional lipid-lowering therapy is unclear in light of recent evidence that demonstrates a lack of improved cardiovascular outcomes with combination therapy. The purpose of this review is to summarize and interpret evidence that evaluates nonstatin drug classes in reducing cardiovascular outcomes, to provide recommendations for use of nonstatin therapies in clinical practice, and to review emerging nonstatin therapies for management of dyslipidemia. Methods Relevant articles were identified through searches of PubMed, International Pharmaceutical Abstracts, and the Cochrane Database of Systematic Reviews by using the terms niacin, omega-3 fatty acids (FAs), clofibrate, fibrate, fenofibrate, fenofibric acid, gemfibrozil, cholestyramine, colestipol, colesevelam, ezetimibe, proprotein convertase subtilisin/kexin 9 (PCSK9), cholesteryl ester transfer protein (CETP), and cardiovascular outcomes. Only English language, human clinical trials, meta-analyses, and systematic reviews were included. Additional references were identified from citations of published articles. Findings Niacin may reduce cardiovascular events as monotherapy; however, recent trials in combination with statins have failed to show a benefit. Trials with omega-3 FAs have failed to demonstrate significant reductions in cardiovascular outcomes. Fibrates may improve cardiovascular outcomes as monotherapy; however, trials in combination with statins have failed to show a benefit, except in those with elevated triglycerides (>200 mg/dL) or low HDL-C (<40 mg/dL). There is a lack of data that evaluates bile acid sequestrant in combination with statin therapy on reducing cardiovascular events. Ezetimibe–statin combination therapy can reduce cardiovascular outcomes in those with chronic kidney disease and following vascular surgery or acute coronary syndrome. Long-term effects of emerging nonstatin therapies (CETP and PCSK9 inhibitors) are currently being evaluated in ongoing Phase III trials. Implications Nonstatin therapies have a limited role in reducing cardiovascular events in those maintained on guideline-directed statin therapy. In certain clinical situations, such as patients who are unable to tolerate statin therapy or recommended intensities of statin therapy, those with persistent severe elevations in triglycerides, or patients with high cardiovascular risk, some nonstatin therapies may be useful in reducing cardiovascular events. Future research is needed to evaluate the role of nonstatin therapies in those who are unable to tolerate guideline-directed statin doses.</description><subject>Anticholesteremic Agents - therapeutic use</subject><subject>bile acid sequestrant</subject><subject>Cardiovascular disease</subject><subject>Cardiovascular Diseases - prevention & control</subject><subject>Cholesterol</subject><subject>Cholesterol Ester Transfer Proteins - therapeutic use</subject><subject>Cholesterol, LDL - blood</subject><subject>Clinical trials</subject><subject>Clofibrate - therapeutic use</subject><subject>Disease Management</subject><subject>Dyslipidemias - drug therapy</subject><subject>ezetimibe</subject><subject>Ezetimibe - therapeutic use</subject><subject>Fatty Acids, Omega-3 - therapeutic use</subject><subject>fenofibrate</subject><subject>Heart attacks</subject><subject>Humans</subject><subject>Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use</subject><subject>Internal Medicine</subject><subject>Medical Education</subject><subject>Mortality</subject><subject>niacin</subject><subject>Niacin - therapeutic use</subject><subject>non-statin therapy</subject><subject>omega-3 fatty acid</subject><subject>Proprotein Convertases - metabolism</subject><subject>Proprotein Convertases - therapeutic use</subject><subject>Risk Factors</subject><subject>Saccharomyces cerevisiae Proteins - therapeutic use</subject><subject>Statins</subject><subject>Triglycerides - blood</subject><subject>United States</subject><issn>0149-2918</issn><issn>1879-114X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqNkU1P3DAQhi1EBVvKX4BIXHpJOuPEcYwQ0oqWFom2UgsSN8txJq2XfCx2FrT_nkTLh8SJ01yeeWfmGcYOERIEzL8sEtu4bvhP3iQcUCSgEgDcYjMspIoRs5ttNgPMVMwVFrvsYwgLAEiV4Dtsl-cZcqnUjJ386rswmMF10dWUtnQUorr30U_TmX_UUjdEfR19XYfGLV1FrTPH0Tz6Q_eOHj6xD7VpAu0_1T12ff7t6uxHfPn7-8XZ_DK2gsMQy1qYEsqKl7YUhSlsSWkOYGwhTVaitSnnkCMYzkkWNstSNGmVk6wqYSRBusc-b3KXvr9bURh064KlpjEd9augUU7HIAg1okdv0EW_8t243USJvOBK8ZGSG8r6PgRPtV561xq_1gh6EqwX-kWwngRrUHoUPHYePOWvypaql75noyMw3wA0ChkleR2so85S5TzZQVe9e8eQ0zcZE-esaW5pTeH1Ih24Bv13-vP0ZhSAoFJIHwFjl6Qw</recordid><startdate>20151001</startdate><enddate>20151001</enddate><creator>Sando, Karen R., PharmD</creator><creator>Knight, Michelle, PharmD</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88C</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M0T</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20151001</creationdate><title>Nonstatin Therapies for Management of Dyslipidemia: A Review</title><author>Sando, Karen R., PharmD ; Knight, Michelle, PharmD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c520t-7f5ab0bd2bcb58a8cbe3600ac87a4b1cc3220610a22e78c4431a3d6e7dd5a7e03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Anticholesteremic Agents - therapeutic use</topic><topic>bile acid sequestrant</topic><topic>Cardiovascular disease</topic><topic>Cardiovascular Diseases - prevention & control</topic><topic>Cholesterol</topic><topic>Cholesterol Ester Transfer Proteins - therapeutic use</topic><topic>Cholesterol, LDL - blood</topic><topic>Clinical trials</topic><topic>Clofibrate - therapeutic use</topic><topic>Disease Management</topic><topic>Dyslipidemias - drug therapy</topic><topic>ezetimibe</topic><topic>Ezetimibe - therapeutic use</topic><topic>Fatty Acids, Omega-3 - therapeutic use</topic><topic>fenofibrate</topic><topic>Heart attacks</topic><topic>Humans</topic><topic>Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use</topic><topic>Internal Medicine</topic><topic>Medical Education</topic><topic>Mortality</topic><topic>niacin</topic><topic>Niacin - therapeutic use</topic><topic>non-statin therapy</topic><topic>omega-3 fatty acid</topic><topic>Proprotein Convertases - metabolism</topic><topic>Proprotein Convertases - therapeutic use</topic><topic>Risk Factors</topic><topic>Saccharomyces cerevisiae Proteins - therapeutic use</topic><topic>Statins</topic><topic>Triglycerides - blood</topic><topic>United States</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sando, Karen R., PharmD</creatorcontrib><creatorcontrib>Knight, Michelle, PharmD</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Proquest Nursing & Allied Health Source</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Healthcare Administration Database (Alumni)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Healthcare Administration Database</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sando, Karen R., PharmD</au><au>Knight, Michelle, PharmD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nonstatin Therapies for Management of Dyslipidemia: A Review</atitle><jtitle>Clinical therapeutics</jtitle><addtitle>Clin Ther</addtitle><date>2015-10-01</date><risdate>2015</risdate><volume>37</volume><issue>10</issue><spage>2153</spage><epage>2179</epage><pages>2153-2179</pages><issn>0149-2918</issn><eissn>1879-114X</eissn><abstract>Abstract Purpose Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States. Recently published cholesterol treatment guidelines emphasize the use of statins as the preferred treatment strategy for both primary and secondary prevention of CVD. However, the optimal treatment strategy for patients who cannot tolerate statin therapy or those who need additional lipid-lowering therapy is unclear in light of recent evidence that demonstrates a lack of improved cardiovascular outcomes with combination therapy. The purpose of this review is to summarize and interpret evidence that evaluates nonstatin drug classes in reducing cardiovascular outcomes, to provide recommendations for use of nonstatin therapies in clinical practice, and to review emerging nonstatin therapies for management of dyslipidemia. Methods Relevant articles were identified through searches of PubMed, International Pharmaceutical Abstracts, and the Cochrane Database of Systematic Reviews by using the terms niacin, omega-3 fatty acids (FAs), clofibrate, fibrate, fenofibrate, fenofibric acid, gemfibrozil, cholestyramine, colestipol, colesevelam, ezetimibe, proprotein convertase subtilisin/kexin 9 (PCSK9), cholesteryl ester transfer protein (CETP), and cardiovascular outcomes. Only English language, human clinical trials, meta-analyses, and systematic reviews were included. Additional references were identified from citations of published articles. Findings Niacin may reduce cardiovascular events as monotherapy; however, recent trials in combination with statins have failed to show a benefit. Trials with omega-3 FAs have failed to demonstrate significant reductions in cardiovascular outcomes. Fibrates may improve cardiovascular outcomes as monotherapy; however, trials in combination with statins have failed to show a benefit, except in those with elevated triglycerides (>200 mg/dL) or low HDL-C (<40 mg/dL). There is a lack of data that evaluates bile acid sequestrant in combination with statin therapy on reducing cardiovascular events. Ezetimibe–statin combination therapy can reduce cardiovascular outcomes in those with chronic kidney disease and following vascular surgery or acute coronary syndrome. Long-term effects of emerging nonstatin therapies (CETP and PCSK9 inhibitors) are currently being evaluated in ongoing Phase III trials. Implications Nonstatin therapies have a limited role in reducing cardiovascular events in those maintained on guideline-directed statin therapy. In certain clinical situations, such as patients who are unable to tolerate statin therapy or recommended intensities of statin therapy, those with persistent severe elevations in triglycerides, or patients with high cardiovascular risk, some nonstatin therapies may be useful in reducing cardiovascular events. Future research is needed to evaluate the role of nonstatin therapies in those who are unable to tolerate guideline-directed statin doses.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>26412799</pmid><doi>10.1016/j.clinthera.2015.09.001</doi><tpages>27</tpages></addata></record> |
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| subjects | Anticholesteremic Agents - therapeutic use bile acid sequestrant Cardiovascular disease Cardiovascular Diseases - prevention & control Cholesterol Cholesterol Ester Transfer Proteins - therapeutic use Cholesterol, LDL - blood Clinical trials Clofibrate - therapeutic use Disease Management Dyslipidemias - drug therapy ezetimibe Ezetimibe - therapeutic use Fatty Acids, Omega-3 - therapeutic use fenofibrate Heart attacks Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use Internal Medicine Medical Education Mortality niacin Niacin - therapeutic use non-statin therapy omega-3 fatty acid Proprotein Convertases - metabolism Proprotein Convertases - therapeutic use Risk Factors Saccharomyces cerevisiae Proteins - therapeutic use Statins Triglycerides - blood United States |
| title | Nonstatin Therapies for Management of Dyslipidemia: A Review |
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