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Intensification of Statin Therapy Results in a Rapid Reduction in Atherosclerotic Inflammation

Objectives The study sought to test whether high-dose statin treatment would result in greater reductions in plaque inflammation than low-dose statins, using fluorodeoxyglucose-positron emission tomography/computed tomographic imaging (FDG-PET/CT). Background Intensification of statin therapy reduce...

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Published in:Journal of the American College of Cardiology 2013-09, Vol.62 (10), p.909-917
Main Authors: Tawakol, Ahmed, MD, Fayad, Zahi A., PhD, Mogg, Robin, PhD, Alon, Achilles, PharmD, Klimas, Michael T., PhD, Dansky, Hayes, MD, Subramanian, Sharath S., MD, Abdelbaky, Amr, MD, Rudd, James H.F., MD, PhD, Farkouh, Michael E., MD, MSc, Nunes, Irene O., PhD, Beals, Chan R., MD, Shankar, Sudha S., MD
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container_issue 10
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container_title Journal of the American College of Cardiology
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creator Tawakol, Ahmed, MD
Fayad, Zahi A., PhD
Mogg, Robin, PhD
Alon, Achilles, PharmD
Klimas, Michael T., PhD
Dansky, Hayes, MD
Subramanian, Sharath S., MD
Abdelbaky, Amr, MD
Rudd, James H.F., MD, PhD
Farkouh, Michael E., MD, MSc
Nunes, Irene O., PhD
Beals, Chan R., MD
Shankar, Sudha S., MD
description Objectives The study sought to test whether high-dose statin treatment would result in greater reductions in plaque inflammation than low-dose statins, using fluorodeoxyglucose-positron emission tomography/computed tomographic imaging (FDG-PET/CT). Background Intensification of statin therapy reduces major cardiovascular events. Methods Adults with risk factors or with established atherosclerosis, who were not taking high-dose statins (n = 83), were randomized to atorvastatin 10 versus 80 mg in a double-blind, multicenter trial. FDG-PET/CT imaging of the ascending thoracic aorta and carotid arteries was performed at baseline, 4, and 12 weeks after randomization and target-to-background ratio (TBR) of FDG uptake within the artery wall was assessed while blinded to time points and treatment. Results Sixty-seven subjects completed the study, providing imaging data for analysis. At 12 weeks, inflammation (TBR) in the index vessel was significantly reduced from baseline with atorvastatin 80 mg (% reduction [95% confidence interval]: 14.42% [8.7% to 19.8%]; p < 0.001), but not atorvastatin 10 mg (% reduction: 4.2% [–2.3% to 10.4%]; p > 0.1). Atorvastatin 80 mg resulted in significant additional relative reductions in TBR versus atorvastatin 10 mg (10.6% [2.2% to 18.3%]; p = 0.01) at week 12. Reductions from baseline in TBR were seen as early as 4 weeks after randomization with atorvastatin 10 mg (6.4% reduction, p < 0.05) and 80 mg (12.5% reduction, p < 0.001). Changes in TBR did not correlate with lipid profile changes. Conclusions Statin therapy produced significant rapid dose-dependent reductions in FDG uptake that may represent changes in atherosclerotic plaque inflammation. FDG-PET imaging may be useful in detecting early treatment effects in patients at risk or with established atherosclerosis. (Evaluate the Utility of 18FDG-PET as a Tool to Quantify Atherosclerotic Plaque; NCT00703261 )
doi_str_mv 10.1016/j.jacc.2013.04.066
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Background Intensification of statin therapy reduces major cardiovascular events. Methods Adults with risk factors or with established atherosclerosis, who were not taking high-dose statins (n = 83), were randomized to atorvastatin 10 versus 80 mg in a double-blind, multicenter trial. FDG-PET/CT imaging of the ascending thoracic aorta and carotid arteries was performed at baseline, 4, and 12 weeks after randomization and target-to-background ratio (TBR) of FDG uptake within the artery wall was assessed while blinded to time points and treatment. Results Sixty-seven subjects completed the study, providing imaging data for analysis. At 12 weeks, inflammation (TBR) in the index vessel was significantly reduced from baseline with atorvastatin 80 mg (% reduction [95% confidence interval]: 14.42% [8.7% to 19.8%]; p &lt; 0.001), but not atorvastatin 10 mg (% reduction: 4.2% [–2.3% to 10.4%]; p &gt; 0.1). Atorvastatin 80 mg resulted in significant additional relative reductions in TBR versus atorvastatin 10 mg (10.6% [2.2% to 18.3%]; p = 0.01) at week 12. Reductions from baseline in TBR were seen as early as 4 weeks after randomization with atorvastatin 10 mg (6.4% reduction, p &lt; 0.05) and 80 mg (12.5% reduction, p &lt; 0.001). Changes in TBR did not correlate with lipid profile changes. Conclusions Statin therapy produced significant rapid dose-dependent reductions in FDG uptake that may represent changes in atherosclerotic plaque inflammation. FDG-PET imaging may be useful in detecting early treatment effects in patients at risk or with established atherosclerosis. (Evaluate the Utility of 18FDG-PET as a Tool to Quantify Atherosclerotic Plaque; NCT00703261 )</description><identifier>ISSN: 0735-1097</identifier><identifier>EISSN: 1558-3597</identifier><identifier>DOI: 10.1016/j.jacc.2013.04.066</identifier><language>eng</language><publisher>New York: Elsevier Inc</publisher><subject>atherosclerosis ; atorvastatin ; Body mass index ; Calcification ; Cardiology ; Cardiovascular ; Cardiovascular disease ; Cholesterol ; Confidence intervals ; Diabetes ; Drug therapy ; Family medical history ; FDG ; Gene expression ; inflammation ; Internal Medicine ; Lipoproteins ; plaque ; Statins</subject><ispartof>Journal of the American College of Cardiology, 2013-09, Vol.62 (10), p.909-917</ispartof><rights>American College of Cardiology Foundation</rights><rights>2013 American College of Cardiology Foundation</rights><rights>Copyright Elsevier Limited Sep 3, 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2948-d3937d8ee8319eff18dd78e6fcf205083b839dbbced2f976ccc93adc4cc4b9643</citedby><cites>FETCH-LOGICAL-c2948-d3937d8ee8319eff18dd78e6fcf205083b839dbbced2f976ccc93adc4cc4b9643</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids></links><search><creatorcontrib>Tawakol, Ahmed, MD</creatorcontrib><creatorcontrib>Fayad, Zahi A., PhD</creatorcontrib><creatorcontrib>Mogg, Robin, PhD</creatorcontrib><creatorcontrib>Alon, Achilles, PharmD</creatorcontrib><creatorcontrib>Klimas, Michael T., PhD</creatorcontrib><creatorcontrib>Dansky, Hayes, MD</creatorcontrib><creatorcontrib>Subramanian, Sharath S., MD</creatorcontrib><creatorcontrib>Abdelbaky, Amr, MD</creatorcontrib><creatorcontrib>Rudd, James H.F., MD, PhD</creatorcontrib><creatorcontrib>Farkouh, Michael E., MD, MSc</creatorcontrib><creatorcontrib>Nunes, Irene O., PhD</creatorcontrib><creatorcontrib>Beals, Chan R., MD</creatorcontrib><creatorcontrib>Shankar, Sudha S., MD</creatorcontrib><title>Intensification of Statin Therapy Results in a Rapid Reduction in Atherosclerotic Inflammation</title><title>Journal of the American College of Cardiology</title><description>Objectives The study sought to test whether high-dose statin treatment would result in greater reductions in plaque inflammation than low-dose statins, using fluorodeoxyglucose-positron emission tomography/computed tomographic imaging (FDG-PET/CT). Background Intensification of statin therapy reduces major cardiovascular events. Methods Adults with risk factors or with established atherosclerosis, who were not taking high-dose statins (n = 83), were randomized to atorvastatin 10 versus 80 mg in a double-blind, multicenter trial. FDG-PET/CT imaging of the ascending thoracic aorta and carotid arteries was performed at baseline, 4, and 12 weeks after randomization and target-to-background ratio (TBR) of FDG uptake within the artery wall was assessed while blinded to time points and treatment. Results Sixty-seven subjects completed the study, providing imaging data for analysis. At 12 weeks, inflammation (TBR) in the index vessel was significantly reduced from baseline with atorvastatin 80 mg (% reduction [95% confidence interval]: 14.42% [8.7% to 19.8%]; p &lt; 0.001), but not atorvastatin 10 mg (% reduction: 4.2% [–2.3% to 10.4%]; p &gt; 0.1). Atorvastatin 80 mg resulted in significant additional relative reductions in TBR versus atorvastatin 10 mg (10.6% [2.2% to 18.3%]; p = 0.01) at week 12. Reductions from baseline in TBR were seen as early as 4 weeks after randomization with atorvastatin 10 mg (6.4% reduction, p &lt; 0.05) and 80 mg (12.5% reduction, p &lt; 0.001). Changes in TBR did not correlate with lipid profile changes. Conclusions Statin therapy produced significant rapid dose-dependent reductions in FDG uptake that may represent changes in atherosclerotic plaque inflammation. FDG-PET imaging may be useful in detecting early treatment effects in patients at risk or with established atherosclerosis. (Evaluate the Utility of 18FDG-PET as a Tool to Quantify Atherosclerotic Plaque; NCT00703261 )</description><subject>atherosclerosis</subject><subject>atorvastatin</subject><subject>Body mass index</subject><subject>Calcification</subject><subject>Cardiology</subject><subject>Cardiovascular</subject><subject>Cardiovascular disease</subject><subject>Cholesterol</subject><subject>Confidence intervals</subject><subject>Diabetes</subject><subject>Drug therapy</subject><subject>Family medical history</subject><subject>FDG</subject><subject>Gene expression</subject><subject>inflammation</subject><subject>Internal Medicine</subject><subject>Lipoproteins</subject><subject>plaque</subject><subject>Statins</subject><issn>0735-1097</issn><issn>1558-3597</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNp9kV9r2zAUxcVYYVm2L7AnQ5_tXkn-I0EplLCtgcAg7V4nlKsrJs-xM8sp5NtXbgqFPvRFEodzrg6_y9g3DgUHXl-1RWsRCwFcFlAWUNcf2IJXlcplpZuPbAGNrHIOuvnEPsfYAkCtuF6wP-t-oj4GH9BOYeizwWf3U3r22cNfGu3hlG0pHrspZkmy2dYegkuSO-KzPYm3UzIOEbt0TgGzde87u98_j_vCLrztIn19uZfs94_vD6u7fPPr53p1u8lR6FLlTmrZOEWkJNfkPVfONYpqj15ABUrulNRut0NywuumRkQtrcMSsdzpupRLdnmeexiH_0eKk2mH49inLw2vy0poDUollzi7MPWNI3lzGMPejifDwcwcTWtmjmbmaKA0iWMKXZ9DlPo_BhpNxEB9qhJGwsm4Ibwfv3kTxy70iXb3j04UX2uaKAyY-3lR8564BAFKCPkEE-uSDw</recordid><startdate>20130903</startdate><enddate>20130903</enddate><creator>Tawakol, Ahmed, MD</creator><creator>Fayad, Zahi A., PhD</creator><creator>Mogg, Robin, PhD</creator><creator>Alon, Achilles, PharmD</creator><creator>Klimas, Michael T., PhD</creator><creator>Dansky, Hayes, MD</creator><creator>Subramanian, Sharath S., MD</creator><creator>Abdelbaky, Amr, MD</creator><creator>Rudd, James H.F., MD, PhD</creator><creator>Farkouh, Michael E., MD, MSc</creator><creator>Nunes, Irene O., PhD</creator><creator>Beals, Chan R., MD</creator><creator>Shankar, Sudha S., MD</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><scope>6I.</scope><scope>AAFTH</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TK</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope></search><sort><creationdate>20130903</creationdate><title>Intensification of Statin Therapy Results in a Rapid Reduction in Atherosclerotic Inflammation</title><author>Tawakol, Ahmed, MD ; Fayad, Zahi A., PhD ; Mogg, Robin, PhD ; Alon, Achilles, PharmD ; Klimas, Michael T., PhD ; Dansky, Hayes, MD ; Subramanian, Sharath S., MD ; Abdelbaky, Amr, MD ; Rudd, James H.F., MD, PhD ; Farkouh, Michael E., MD, MSc ; Nunes, Irene O., PhD ; Beals, Chan R., MD ; Shankar, Sudha S., MD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2948-d3937d8ee8319eff18dd78e6fcf205083b839dbbced2f976ccc93adc4cc4b9643</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>atherosclerosis</topic><topic>atorvastatin</topic><topic>Body mass index</topic><topic>Calcification</topic><topic>Cardiology</topic><topic>Cardiovascular</topic><topic>Cardiovascular disease</topic><topic>Cholesterol</topic><topic>Confidence intervals</topic><topic>Diabetes</topic><topic>Drug therapy</topic><topic>Family medical history</topic><topic>FDG</topic><topic>Gene expression</topic><topic>inflammation</topic><topic>Internal Medicine</topic><topic>Lipoproteins</topic><topic>plaque</topic><topic>Statins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tawakol, Ahmed, MD</creatorcontrib><creatorcontrib>Fayad, Zahi A., PhD</creatorcontrib><creatorcontrib>Mogg, Robin, PhD</creatorcontrib><creatorcontrib>Alon, Achilles, PharmD</creatorcontrib><creatorcontrib>Klimas, Michael T., PhD</creatorcontrib><creatorcontrib>Dansky, Hayes, MD</creatorcontrib><creatorcontrib>Subramanian, Sharath S., MD</creatorcontrib><creatorcontrib>Abdelbaky, Amr, MD</creatorcontrib><creatorcontrib>Rudd, James H.F., MD, PhD</creatorcontrib><creatorcontrib>Farkouh, Michael E., MD, MSc</creatorcontrib><creatorcontrib>Nunes, Irene O., PhD</creatorcontrib><creatorcontrib>Beals, Chan R., MD</creatorcontrib><creatorcontrib>Shankar, Sudha S., MD</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Nursing &amp; Allied Health Premium</collection><jtitle>Journal of the American College of Cardiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tawakol, Ahmed, MD</au><au>Fayad, Zahi A., PhD</au><au>Mogg, Robin, PhD</au><au>Alon, Achilles, PharmD</au><au>Klimas, Michael T., PhD</au><au>Dansky, Hayes, MD</au><au>Subramanian, Sharath S., MD</au><au>Abdelbaky, Amr, MD</au><au>Rudd, James H.F., MD, PhD</au><au>Farkouh, Michael E., MD, MSc</au><au>Nunes, Irene O., PhD</au><au>Beals, Chan R., MD</au><au>Shankar, Sudha S., MD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Intensification of Statin Therapy Results in a Rapid Reduction in Atherosclerotic Inflammation</atitle><jtitle>Journal of the American College of Cardiology</jtitle><date>2013-09-03</date><risdate>2013</risdate><volume>62</volume><issue>10</issue><spage>909</spage><epage>917</epage><pages>909-917</pages><issn>0735-1097</issn><eissn>1558-3597</eissn><abstract>Objectives The study sought to test whether high-dose statin treatment would result in greater reductions in plaque inflammation than low-dose statins, using fluorodeoxyglucose-positron emission tomography/computed tomographic imaging (FDG-PET/CT). Background Intensification of statin therapy reduces major cardiovascular events. Methods Adults with risk factors or with established atherosclerosis, who were not taking high-dose statins (n = 83), were randomized to atorvastatin 10 versus 80 mg in a double-blind, multicenter trial. FDG-PET/CT imaging of the ascending thoracic aorta and carotid arteries was performed at baseline, 4, and 12 weeks after randomization and target-to-background ratio (TBR) of FDG uptake within the artery wall was assessed while blinded to time points and treatment. Results Sixty-seven subjects completed the study, providing imaging data for analysis. At 12 weeks, inflammation (TBR) in the index vessel was significantly reduced from baseline with atorvastatin 80 mg (% reduction [95% confidence interval]: 14.42% [8.7% to 19.8%]; p &lt; 0.001), but not atorvastatin 10 mg (% reduction: 4.2% [–2.3% to 10.4%]; p &gt; 0.1). Atorvastatin 80 mg resulted in significant additional relative reductions in TBR versus atorvastatin 10 mg (10.6% [2.2% to 18.3%]; p = 0.01) at week 12. Reductions from baseline in TBR were seen as early as 4 weeks after randomization with atorvastatin 10 mg (6.4% reduction, p &lt; 0.05) and 80 mg (12.5% reduction, p &lt; 0.001). Changes in TBR did not correlate with lipid profile changes. Conclusions Statin therapy produced significant rapid dose-dependent reductions in FDG uptake that may represent changes in atherosclerotic plaque inflammation. FDG-PET imaging may be useful in detecting early treatment effects in patients at risk or with established atherosclerosis. (Evaluate the Utility of 18FDG-PET as a Tool to Quantify Atherosclerotic Plaque; NCT00703261 )</abstract><cop>New York</cop><pub>Elsevier Inc</pub><doi>10.1016/j.jacc.2013.04.066</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
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subjects atherosclerosis
atorvastatin
Body mass index
Calcification
Cardiology
Cardiovascular
Cardiovascular disease
Cholesterol
Confidence intervals
Diabetes
Drug therapy
Family medical history
FDG
Gene expression
inflammation
Internal Medicine
Lipoproteins
plaque
Statins
title Intensification of Statin Therapy Results in a Rapid Reduction in Atherosclerotic Inflammation
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