Pharmacodynamic Evaluation of Switching From Ticagrelor to Prasugrel in Patients With Stable Coronary Artery Disease: Results of the SWAP-2 Study (Switching Anti Platelet-2)
The goal of this study was to evaluate the pharmacodynamic effects of switching patients from ticagrelor to prasugrel. Clinicians may need to switch between more potent P2Y12 inhibitors because of adverse effects or switch to the use of a once-daily dosing regimen due to compliance issues. After a 3...
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| Veröffentlicht in: | Journal of the American College of Cardiology 2014-04, Vol.63 (15), p.1500-1509 |
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| creator | ANGIOLILLO, Dominick J CURZEN, Nicholas GURBEL, Paul VAITKUS, Paul LIPKIN, Fred WEI LI JAKUBOWSKI, Joseph A ZETTLER, Marjorie EFFRON, Mark B TRENK, Dietmar |
| description | The goal of this study was to evaluate the pharmacodynamic effects of switching patients from ticagrelor to prasugrel.
Clinicians may need to switch between more potent P2Y12 inhibitors because of adverse effects or switch to the use of a once-daily dosing regimen due to compliance issues.
After a 3- to 5-day run-in phase with a ticagrelor 180-mg loading dose (LD) followed by a ticagrelor 90-mg twice-daily maintenance dose (MD), aspirin-treated patients (N = 110) with stable coronary artery disease were randomized to continue ticagrelor or switch to prasugrel 10-mg once-daily MD, with or without a 60-mg LD. Pharmacodynamic assessments were defined according to P2Y12 reaction unit (PRU) (P2Y12 assay) and platelet reactivity index (vasodilator-stimulated phosphoprotein phosphorylation assay) at baseline (before and after the run-in phase) and 2, 4, 24, and 48 h and 7 days after randomization.
Platelet reactivity was significantly greater at 24 and 48 h after switching to prasugrel versus continued therapy with ticagrelor, although to a lesser extent in those receiving an LD. Mean PRU remained significantly higher in the combined prasugrel groups versus the ticagrelor group (least-squares mean difference: 46 [95% confidence interval 25 to 67]) and did not meet the primary noninferiority endpoint (upper limit of the confidence interval ≤45), although PRU in the prasugrel cohort was lower at 7 days than at 24 or 48 h. Accordingly, rates of high on-treatment platelet reactivity were higher at 24 and 48 h in both prasugrel groups. At 7 days, there was no difference in high on-treatment platelet reactivity rate between the combined prasugrel and ticagrelor groups.
Compared with continued ticagrelor therapy, switching from ticagrelor to prasugrel therapy was associated with an increase in platelet reactivity that was partially mitigated by the administration of an LD. |
| doi_str_mv | 10.1016/j.jacc.2013.11.032 |
| format | Article |
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Clinicians may need to switch between more potent P2Y12 inhibitors because of adverse effects or switch to the use of a once-daily dosing regimen due to compliance issues.
After a 3- to 5-day run-in phase with a ticagrelor 180-mg loading dose (LD) followed by a ticagrelor 90-mg twice-daily maintenance dose (MD), aspirin-treated patients (N = 110) with stable coronary artery disease were randomized to continue ticagrelor or switch to prasugrel 10-mg once-daily MD, with or without a 60-mg LD. Pharmacodynamic assessments were defined according to P2Y12 reaction unit (PRU) (P2Y12 assay) and platelet reactivity index (vasodilator-stimulated phosphoprotein phosphorylation assay) at baseline (before and after the run-in phase) and 2, 4, 24, and 48 h and 7 days after randomization.
Platelet reactivity was significantly greater at 24 and 48 h after switching to prasugrel versus continued therapy with ticagrelor, although to a lesser extent in those receiving an LD. Mean PRU remained significantly higher in the combined prasugrel groups versus the ticagrelor group (least-squares mean difference: 46 [95% confidence interval 25 to 67]) and did not meet the primary noninferiority endpoint (upper limit of the confidence interval ≤45), although PRU in the prasugrel cohort was lower at 7 days than at 24 or 48 h. Accordingly, rates of high on-treatment platelet reactivity were higher at 24 and 48 h in both prasugrel groups. At 7 days, there was no difference in high on-treatment platelet reactivity rate between the combined prasugrel and ticagrelor groups.
Compared with continued ticagrelor therapy, switching from ticagrelor to prasugrel therapy was associated with an increase in platelet reactivity that was partially mitigated by the administration of an LD.</description><identifier>ISSN: 0735-1097</identifier><identifier>EISSN: 1558-3597</identifier><identifier>DOI: 10.1016/j.jacc.2013.11.032</identifier><identifier>PMID: 24333493</identifier><identifier>CODEN: JACCDI</identifier><language>eng</language><publisher>New York, NY: Elsevier</publisher><subject>Adenosine - administration & dosage ; Adenosine - analogs & derivatives ; Adenosine - pharmacokinetics ; Adolescent ; Adult ; Aged ; Biological and medical sciences ; Blood Platelets - drug effects ; Cardiology. Vascular system ; Coronary Artery Disease - drug therapy ; Coronary Artery Disease - metabolism ; Coronary heart disease ; Dose-Response Relationship, Drug ; Double-Blind Method ; Female ; Follow-Up Studies ; Heart ; Humans ; Male ; Medical sciences ; Middle Aged ; Piperazines - administration & dosage ; Piperazines - pharmacokinetics ; Platelet Function Tests ; Prasugrel Hydrochloride ; Purinergic P2Y Receptor Antagonists - administration & dosage ; Purinergic P2Y Receptor Antagonists - pharmacokinetics ; Thiophenes - administration & dosage ; Thiophenes - pharmacokinetics ; Treatment Outcome ; Young Adult</subject><ispartof>Journal of the American College of Cardiology, 2014-04, Vol.63 (15), p.1500-1509</ispartof><rights>2015 INIST-CNRS</rights><rights>Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28438084$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24333493$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>ANGIOLILLO, Dominick J</creatorcontrib><creatorcontrib>CURZEN, Nicholas</creatorcontrib><creatorcontrib>GURBEL, Paul</creatorcontrib><creatorcontrib>VAITKUS, Paul</creatorcontrib><creatorcontrib>LIPKIN, Fred</creatorcontrib><creatorcontrib>WEI LI</creatorcontrib><creatorcontrib>JAKUBOWSKI, Joseph A</creatorcontrib><creatorcontrib>ZETTLER, Marjorie</creatorcontrib><creatorcontrib>EFFRON, Mark B</creatorcontrib><creatorcontrib>TRENK, Dietmar</creatorcontrib><title>Pharmacodynamic Evaluation of Switching From Ticagrelor to Prasugrel in Patients With Stable Coronary Artery Disease: Results of the SWAP-2 Study (Switching Anti Platelet-2)</title><title>Journal of the American College of Cardiology</title><addtitle>J Am Coll Cardiol</addtitle><description>The goal of this study was to evaluate the pharmacodynamic effects of switching patients from ticagrelor to prasugrel.
Clinicians may need to switch between more potent P2Y12 inhibitors because of adverse effects or switch to the use of a once-daily dosing regimen due to compliance issues.
After a 3- to 5-day run-in phase with a ticagrelor 180-mg loading dose (LD) followed by a ticagrelor 90-mg twice-daily maintenance dose (MD), aspirin-treated patients (N = 110) with stable coronary artery disease were randomized to continue ticagrelor or switch to prasugrel 10-mg once-daily MD, with or without a 60-mg LD. Pharmacodynamic assessments were defined according to P2Y12 reaction unit (PRU) (P2Y12 assay) and platelet reactivity index (vasodilator-stimulated phosphoprotein phosphorylation assay) at baseline (before and after the run-in phase) and 2, 4, 24, and 48 h and 7 days after randomization.
Platelet reactivity was significantly greater at 24 and 48 h after switching to prasugrel versus continued therapy with ticagrelor, although to a lesser extent in those receiving an LD. Mean PRU remained significantly higher in the combined prasugrel groups versus the ticagrelor group (least-squares mean difference: 46 [95% confidence interval 25 to 67]) and did not meet the primary noninferiority endpoint (upper limit of the confidence interval ≤45), although PRU in the prasugrel cohort was lower at 7 days than at 24 or 48 h. Accordingly, rates of high on-treatment platelet reactivity were higher at 24 and 48 h in both prasugrel groups. At 7 days, there was no difference in high on-treatment platelet reactivity rate between the combined prasugrel and ticagrelor groups.
Compared with continued ticagrelor therapy, switching from ticagrelor to prasugrel therapy was associated with an increase in platelet reactivity that was partially mitigated by the administration of an LD.</description><subject>Adenosine - administration & dosage</subject><subject>Adenosine - analogs & derivatives</subject><subject>Adenosine - pharmacokinetics</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Biological and medical sciences</subject><subject>Blood Platelets - drug effects</subject><subject>Cardiology. Vascular system</subject><subject>Coronary Artery Disease - drug therapy</subject><subject>Coronary Artery Disease - metabolism</subject><subject>Coronary heart disease</subject><subject>Dose-Response Relationship, Drug</subject><subject>Double-Blind Method</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Heart</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Piperazines - administration & dosage</subject><subject>Piperazines - pharmacokinetics</subject><subject>Platelet Function Tests</subject><subject>Prasugrel Hydrochloride</subject><subject>Purinergic P2Y Receptor Antagonists - administration & dosage</subject><subject>Purinergic P2Y Receptor Antagonists - pharmacokinetics</subject><subject>Thiophenes - administration & dosage</subject><subject>Thiophenes - pharmacokinetics</subject><subject>Treatment Outcome</subject><subject>Young Adult</subject><issn>0735-1097</issn><issn>1558-3597</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkE9v1DAQxS0EokvhC3BAviCVQ4L_JE7CbbW0gFSJiC3qcTVxJl2vHHuxHdB-KL4jRizqZZ5G-r15mkfIa85Kzrh6fygPoHUpGJcl5yWT4glZ8bpuC1l3zVOyYo2sC8665oK8iPHAGFMt756TC1FJKatOrsjvfg9hBu3Hk4PZaHr9E-wCyXhH_US3v0zSe-Me6E3wM70zGh4CWh9o8rQPEJe_KzWO9tmDLkV6b9KebhMMFunGB-8gnOg6JMzy0USEiB_oN4yLzXCOSHuk2_t1X4jsWsYTvXoMXbtkaG8hocVUiHcvybMJbMRXZ70k32-u7zafi9uvn75s1rfFUVQ8FWoSTdsxLVGpQVVcSt1WqtFKSNmJgVVS8VYO1aRqBZ1GrbBqRsFgrLVuEOQlufp39xj8jwVj2s0marQWHPol7njNmzZXyVlG35zRZZhx3B2DmfPHu_8VZ-DtGYCowU4BnDbxkWsr2bI8_gC7O4zN</recordid><startdate>20140422</startdate><enddate>20140422</enddate><creator>ANGIOLILLO, Dominick J</creator><creator>CURZEN, Nicholas</creator><creator>GURBEL, Paul</creator><creator>VAITKUS, Paul</creator><creator>LIPKIN, Fred</creator><creator>WEI LI</creator><creator>JAKUBOWSKI, Joseph A</creator><creator>ZETTLER, Marjorie</creator><creator>EFFRON, Mark B</creator><creator>TRENK, Dietmar</creator><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20140422</creationdate><title>Pharmacodynamic Evaluation of Switching From Ticagrelor to Prasugrel in Patients With Stable Coronary Artery Disease: Results of the SWAP-2 Study (Switching Anti Platelet-2)</title><author>ANGIOLILLO, Dominick J ; CURZEN, Nicholas ; GURBEL, Paul ; VAITKUS, Paul ; LIPKIN, Fred ; WEI LI ; JAKUBOWSKI, Joseph A ; ZETTLER, Marjorie ; EFFRON, Mark B ; TRENK, Dietmar</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p241t-6f27890c3e66b64133c8467c623392b0436183b4f656a9cec6e47d20ad5cc7ea3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adenosine - administration & dosage</topic><topic>Adenosine - analogs & derivatives</topic><topic>Adenosine - pharmacokinetics</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Biological and medical sciences</topic><topic>Blood Platelets - drug effects</topic><topic>Cardiology. Vascular system</topic><topic>Coronary Artery Disease - drug therapy</topic><topic>Coronary Artery Disease - metabolism</topic><topic>Coronary heart disease</topic><topic>Dose-Response Relationship, Drug</topic><topic>Double-Blind Method</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Heart</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Piperazines - administration & dosage</topic><topic>Piperazines - pharmacokinetics</topic><topic>Platelet Function Tests</topic><topic>Prasugrel Hydrochloride</topic><topic>Purinergic P2Y Receptor Antagonists - administration & dosage</topic><topic>Purinergic P2Y Receptor Antagonists - pharmacokinetics</topic><topic>Thiophenes - administration & dosage</topic><topic>Thiophenes - pharmacokinetics</topic><topic>Treatment Outcome</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>ANGIOLILLO, Dominick J</creatorcontrib><creatorcontrib>CURZEN, Nicholas</creatorcontrib><creatorcontrib>GURBEL, Paul</creatorcontrib><creatorcontrib>VAITKUS, Paul</creatorcontrib><creatorcontrib>LIPKIN, Fred</creatorcontrib><creatorcontrib>WEI LI</creatorcontrib><creatorcontrib>JAKUBOWSKI, Joseph A</creatorcontrib><creatorcontrib>ZETTLER, Marjorie</creatorcontrib><creatorcontrib>EFFRON, Mark B</creatorcontrib><creatorcontrib>TRENK, Dietmar</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of the American College of Cardiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>ANGIOLILLO, Dominick J</au><au>CURZEN, Nicholas</au><au>GURBEL, Paul</au><au>VAITKUS, Paul</au><au>LIPKIN, Fred</au><au>WEI LI</au><au>JAKUBOWSKI, Joseph A</au><au>ZETTLER, Marjorie</au><au>EFFRON, Mark B</au><au>TRENK, Dietmar</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacodynamic Evaluation of Switching From Ticagrelor to Prasugrel in Patients With Stable Coronary Artery Disease: Results of the SWAP-2 Study (Switching Anti Platelet-2)</atitle><jtitle>Journal of the American College of Cardiology</jtitle><addtitle>J Am Coll Cardiol</addtitle><date>2014-04-22</date><risdate>2014</risdate><volume>63</volume><issue>15</issue><spage>1500</spage><epage>1509</epage><pages>1500-1509</pages><issn>0735-1097</issn><eissn>1558-3597</eissn><coden>JACCDI</coden><abstract>The goal of this study was to evaluate the pharmacodynamic effects of switching patients from ticagrelor to prasugrel.
Clinicians may need to switch between more potent P2Y12 inhibitors because of adverse effects or switch to the use of a once-daily dosing regimen due to compliance issues.
After a 3- to 5-day run-in phase with a ticagrelor 180-mg loading dose (LD) followed by a ticagrelor 90-mg twice-daily maintenance dose (MD), aspirin-treated patients (N = 110) with stable coronary artery disease were randomized to continue ticagrelor or switch to prasugrel 10-mg once-daily MD, with or without a 60-mg LD. Pharmacodynamic assessments were defined according to P2Y12 reaction unit (PRU) (P2Y12 assay) and platelet reactivity index (vasodilator-stimulated phosphoprotein phosphorylation assay) at baseline (before and after the run-in phase) and 2, 4, 24, and 48 h and 7 days after randomization.
Platelet reactivity was significantly greater at 24 and 48 h after switching to prasugrel versus continued therapy with ticagrelor, although to a lesser extent in those receiving an LD. Mean PRU remained significantly higher in the combined prasugrel groups versus the ticagrelor group (least-squares mean difference: 46 [95% confidence interval 25 to 67]) and did not meet the primary noninferiority endpoint (upper limit of the confidence interval ≤45), although PRU in the prasugrel cohort was lower at 7 days than at 24 or 48 h. Accordingly, rates of high on-treatment platelet reactivity were higher at 24 and 48 h in both prasugrel groups. At 7 days, there was no difference in high on-treatment platelet reactivity rate between the combined prasugrel and ticagrelor groups.
Compared with continued ticagrelor therapy, switching from ticagrelor to prasugrel therapy was associated with an increase in platelet reactivity that was partially mitigated by the administration of an LD.</abstract><cop>New York, NY</cop><pub>Elsevier</pub><pmid>24333493</pmid><doi>10.1016/j.jacc.2013.11.032</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elsevier ScienceDirect Journals; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adenosine - administration & dosage Adenosine - analogs & derivatives Adenosine - pharmacokinetics Adolescent Adult Aged Biological and medical sciences Blood Platelets - drug effects Cardiology. Vascular system Coronary Artery Disease - drug therapy Coronary Artery Disease - metabolism Coronary heart disease Dose-Response Relationship, Drug Double-Blind Method Female Follow-Up Studies Heart Humans Male Medical sciences Middle Aged Piperazines - administration & dosage Piperazines - pharmacokinetics Platelet Function Tests Prasugrel Hydrochloride Purinergic P2Y Receptor Antagonists - administration & dosage Purinergic P2Y Receptor Antagonists - pharmacokinetics Thiophenes - administration & dosage Thiophenes - pharmacokinetics Treatment Outcome Young Adult |
| title | Pharmacodynamic Evaluation of Switching From Ticagrelor to Prasugrel in Patients With Stable Coronary Artery Disease: Results of the SWAP-2 Study (Switching Anti Platelet-2) |
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