Statin therapy is not associated with improved outcomes after heart transplantation in children and adolescents
Background Although used routinely, the pleiotropic benefits of statins remain understudied in children after heart transplantation. We hypothesized that statin therapy would reduce the incidence of rejection, cardiac allograft vasculopathy (CAV) and post-transplant lymphoproliferative disease (PTLD...
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| Veröffentlicht in: | The Journal of heart and lung transplantation 2016-04, Vol.35 (4), p.457-465 |
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| container_title | The Journal of heart and lung transplantation |
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| creator | Greenway, Steven C., MS, MD, FRCPC Butts, Ryan, MD Naftel, David C., PhD Pruitt, Elizabeth, MSPH Kirklin, James K., MD Larsen, Ingrid, BScN Urschel, Simon, MD Knecht, Kenneth, MD Law, Yuk, MD |
| description | Background Although used routinely, the pleiotropic benefits of statins remain understudied in children after heart transplantation. We hypothesized that statin therapy would reduce the incidence of rejection, cardiac allograft vasculopathy (CAV) and post-transplant lymphoproliferative disease (PTLD). Methods This study was a retrospective review of 964 pediatric (ages 5 to 18 years) heart transplant recipients in the multicenter Pediatric Heart Transplant Study registry from 2001 to 2012. Patients were excluded if they were undergoing re-transplantation, survived |
| doi_str_mv | 10.1016/j.healun.2015.10.040 |
| format | Article |
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We hypothesized that statin therapy would reduce the incidence of rejection, cardiac allograft vasculopathy (CAV) and post-transplant lymphoproliferative disease (PTLD). Methods This study was a retrospective review of 964 pediatric (ages 5 to 18 years) heart transplant recipients in the multicenter Pediatric Heart Transplant Study registry from 2001 to 2012. Patients were excluded if they were undergoing re-transplantation, survived <1 year post-transplant, or had missing data regarding statin use. The effects of statins beyond the first year were estimated by Kaplan-Meier and Cox regression multivariable analysis for freedom from PTLD, rejection requiring treatment, any severity of CAV, and survival. Results Statin use was variable among participating centers with only 30% to 35% of patients ≥10 years of age started on a statin at <1 year post-transplant. After the first year post-transplant, statin-treated children (average age at transplant 13.24 ± 3.29 years) had significantly earlier rejection (HR 1.42, 95% CI 1.11 to 1.82, p = 0.006) compared with untreated children (transplanted at 12 ± 3.64 years) after adjusting for conventional risk factors for rejection. Freedom from PTLD, CAV and overall survival up to 5 years post-transplant were not affected by statin use, although the number of events was small. Conclusions Statin therapy did not confer a survival benefit and was not associated with delayed onset of PTLD or CAV. Early (<1 year post-transplant) statin therapy was associated with increased later frequency of rejection. These findings suggest that a prospective trial evaluating statin therapy in pediatric heart transplant recipients is warranted.</description><identifier>ISSN: 1053-2498</identifier><identifier>EISSN: 1557-3117</identifier><identifier>DOI: 10.1016/j.healun.2015.10.040</identifier><identifier>PMID: 26746989</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adolescent ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Graft Rejection - drug therapy ; Graft Rejection - epidemiology ; Graft Survival ; Heart Transplantation ; HMG-CoA reductase inhibitors ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use ; Incidence ; Male ; pediatric heart transplantation ; PTLD ; Registries ; rejection ; Retrospective Studies ; Risk Factors ; statin ; Surgery ; Survival Rate - trends ; Time Factors ; United Kingdom - epidemiology ; United States - epidemiology ; vasculopathy</subject><ispartof>The Journal of heart and lung transplantation, 2016-04, Vol.35 (4), p.457-465</ispartof><rights>2016</rights><rights>Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c463t-4b6481fb01cb33711a3ff82d107c85eb2b855d4e5c1fd37d6c6249482b5166bd3</citedby><cites>FETCH-LOGICAL-c463t-4b6481fb01cb33711a3ff82d107c85eb2b855d4e5c1fd37d6c6249482b5166bd3</cites><orcidid>0000-0002-4228-4473 ; 0000-0001-6626-9027</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.healun.2015.10.040$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26746989$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Greenway, Steven C., MS, MD, FRCPC</creatorcontrib><creatorcontrib>Butts, Ryan, MD</creatorcontrib><creatorcontrib>Naftel, David C., PhD</creatorcontrib><creatorcontrib>Pruitt, Elizabeth, MSPH</creatorcontrib><creatorcontrib>Kirklin, James K., MD</creatorcontrib><creatorcontrib>Larsen, Ingrid, BScN</creatorcontrib><creatorcontrib>Urschel, Simon, MD</creatorcontrib><creatorcontrib>Knecht, Kenneth, MD</creatorcontrib><creatorcontrib>Law, Yuk, MD</creatorcontrib><title>Statin therapy is not associated with improved outcomes after heart transplantation in children and adolescents</title><title>The Journal of heart and lung transplantation</title><addtitle>J Heart Lung Transplant</addtitle><description>Background Although used routinely, the pleiotropic benefits of statins remain understudied in children after heart transplantation. We hypothesized that statin therapy would reduce the incidence of rejection, cardiac allograft vasculopathy (CAV) and post-transplant lymphoproliferative disease (PTLD). Methods This study was a retrospective review of 964 pediatric (ages 5 to 18 years) heart transplant recipients in the multicenter Pediatric Heart Transplant Study registry from 2001 to 2012. Patients were excluded if they were undergoing re-transplantation, survived <1 year post-transplant, or had missing data regarding statin use. The effects of statins beyond the first year were estimated by Kaplan-Meier and Cox regression multivariable analysis for freedom from PTLD, rejection requiring treatment, any severity of CAV, and survival. Results Statin use was variable among participating centers with only 30% to 35% of patients ≥10 years of age started on a statin at <1 year post-transplant. After the first year post-transplant, statin-treated children (average age at transplant 13.24 ± 3.29 years) had significantly earlier rejection (HR 1.42, 95% CI 1.11 to 1.82, p = 0.006) compared with untreated children (transplanted at 12 ± 3.64 years) after adjusting for conventional risk factors for rejection. Freedom from PTLD, CAV and overall survival up to 5 years post-transplant were not affected by statin use, although the number of events was small. Conclusions Statin therapy did not confer a survival benefit and was not associated with delayed onset of PTLD or CAV. Early (<1 year post-transplant) statin therapy was associated with increased later frequency of rejection. These findings suggest that a prospective trial evaluating statin therapy in pediatric heart transplant recipients is warranted.</description><subject>Adolescent</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Graft Rejection - drug therapy</subject><subject>Graft Rejection - epidemiology</subject><subject>Graft Survival</subject><subject>Heart Transplantation</subject><subject>HMG-CoA reductase inhibitors</subject><subject>Humans</subject><subject>Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use</subject><subject>Incidence</subject><subject>Male</subject><subject>pediatric heart transplantation</subject><subject>PTLD</subject><subject>Registries</subject><subject>rejection</subject><subject>Retrospective Studies</subject><subject>Risk Factors</subject><subject>statin</subject><subject>Surgery</subject><subject>Survival Rate - trends</subject><subject>Time Factors</subject><subject>United Kingdom - epidemiology</subject><subject>United States - epidemiology</subject><subject>vasculopathy</subject><issn>1053-2498</issn><issn>1557-3117</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUFv1DAQhS0EakvpP0DIRy5ZPHbsZC9IqKKlUiUOBYmb5dgTrZfEXmynaP89jrZw4NKT7dGbN28-E_IW2AYYqA_7zQ7NtIQNZyBracNa9oJcgJRdIwC6l_XOpGh4u-3Pyeuc94wxLiQ_I-dcda3a9tsLEh-KKT7QssNkDkfqMw2xUJNztN4UdPS3Lzvq50OKj_UVl2LjjJmasWCiNUIqtCQT8mEyYfWKgVY_u_OTSxioCY4aFyfMFkPJb8ir0UwZr57OS_L95vO36y_N_dfbu-tP941tlShNO6i2h3FgYAchOgAjxrHnDlhne4kDH3opXYvSwuhE55RVdc-254MEpQYnLsn7k2_N_WvBXPTsa4KphsS4ZA1dt2WcKSGqtD1JbYo5Jxz1IfnZpKMGplfUeq9PqPWKeq1W1LXt3dOEZZjR_Wv6y7YKPp4EWPd89Jh0th6DRecT2qJd9M9N-N_ATj54a6afeMS8j0sKlaEGnblm-mH97vW3QVYT6H6IP5wyqGs</recordid><startdate>20160401</startdate><enddate>20160401</enddate><creator>Greenway, Steven C., MS, MD, FRCPC</creator><creator>Butts, Ryan, MD</creator><creator>Naftel, David C., PhD</creator><creator>Pruitt, Elizabeth, MSPH</creator><creator>Kirklin, James K., MD</creator><creator>Larsen, Ingrid, BScN</creator><creator>Urschel, Simon, MD</creator><creator>Knecht, Kenneth, MD</creator><creator>Law, Yuk, MD</creator><general>Elsevier Inc</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>7X8</scope><orcidid>https://orcid.org/0000-0002-4228-4473</orcidid><orcidid>https://orcid.org/0000-0001-6626-9027</orcidid></search><sort><creationdate>20160401</creationdate><title>Statin therapy is not associated with improved outcomes after heart transplantation in children and adolescents</title><author>Greenway, Steven C., MS, MD, FRCPC ; Butts, Ryan, MD ; Naftel, David C., PhD ; Pruitt, Elizabeth, MSPH ; Kirklin, James K., MD ; Larsen, Ingrid, BScN ; Urschel, Simon, MD ; Knecht, Kenneth, MD ; Law, Yuk, MD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c463t-4b6481fb01cb33711a3ff82d107c85eb2b855d4e5c1fd37d6c6249482b5166bd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adolescent</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Graft Rejection - drug therapy</topic><topic>Graft Rejection - epidemiology</topic><topic>Graft Survival</topic><topic>Heart Transplantation</topic><topic>HMG-CoA reductase inhibitors</topic><topic>Humans</topic><topic>Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use</topic><topic>Incidence</topic><topic>Male</topic><topic>pediatric heart transplantation</topic><topic>PTLD</topic><topic>Registries</topic><topic>rejection</topic><topic>Retrospective Studies</topic><topic>Risk Factors</topic><topic>statin</topic><topic>Surgery</topic><topic>Survival Rate - trends</topic><topic>Time Factors</topic><topic>United Kingdom - epidemiology</topic><topic>United States - epidemiology</topic><topic>vasculopathy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Greenway, Steven C., MS, MD, FRCPC</creatorcontrib><creatorcontrib>Butts, Ryan, MD</creatorcontrib><creatorcontrib>Naftel, David C., PhD</creatorcontrib><creatorcontrib>Pruitt, Elizabeth, MSPH</creatorcontrib><creatorcontrib>Kirklin, James K., MD</creatorcontrib><creatorcontrib>Larsen, Ingrid, BScN</creatorcontrib><creatorcontrib>Urschel, Simon, MD</creatorcontrib><creatorcontrib>Knecht, Kenneth, MD</creatorcontrib><creatorcontrib>Law, Yuk, MD</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of heart and lung transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Greenway, Steven C., MS, MD, FRCPC</au><au>Butts, Ryan, MD</au><au>Naftel, David C., PhD</au><au>Pruitt, Elizabeth, MSPH</au><au>Kirklin, James K., MD</au><au>Larsen, Ingrid, BScN</au><au>Urschel, Simon, MD</au><au>Knecht, Kenneth, MD</au><au>Law, Yuk, MD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Statin therapy is not associated with improved outcomes after heart transplantation in children and adolescents</atitle><jtitle>The Journal of heart and lung transplantation</jtitle><addtitle>J Heart Lung Transplant</addtitle><date>2016-04-01</date><risdate>2016</risdate><volume>35</volume><issue>4</issue><spage>457</spage><epage>465</epage><pages>457-465</pages><issn>1053-2498</issn><eissn>1557-3117</eissn><abstract>Background Although used routinely, the pleiotropic benefits of statins remain understudied in children after heart transplantation. We hypothesized that statin therapy would reduce the incidence of rejection, cardiac allograft vasculopathy (CAV) and post-transplant lymphoproliferative disease (PTLD). Methods This study was a retrospective review of 964 pediatric (ages 5 to 18 years) heart transplant recipients in the multicenter Pediatric Heart Transplant Study registry from 2001 to 2012. Patients were excluded if they were undergoing re-transplantation, survived <1 year post-transplant, or had missing data regarding statin use. The effects of statins beyond the first year were estimated by Kaplan-Meier and Cox regression multivariable analysis for freedom from PTLD, rejection requiring treatment, any severity of CAV, and survival. Results Statin use was variable among participating centers with only 30% to 35% of patients ≥10 years of age started on a statin at <1 year post-transplant. After the first year post-transplant, statin-treated children (average age at transplant 13.24 ± 3.29 years) had significantly earlier rejection (HR 1.42, 95% CI 1.11 to 1.82, p = 0.006) compared with untreated children (transplanted at 12 ± 3.64 years) after adjusting for conventional risk factors for rejection. Freedom from PTLD, CAV and overall survival up to 5 years post-transplant were not affected by statin use, although the number of events was small. Conclusions Statin therapy did not confer a survival benefit and was not associated with delayed onset of PTLD or CAV. Early (<1 year post-transplant) statin therapy was associated with increased later frequency of rejection. These findings suggest that a prospective trial evaluating statin therapy in pediatric heart transplant recipients is warranted.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>26746989</pmid><doi>10.1016/j.healun.2015.10.040</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-4228-4473</orcidid><orcidid>https://orcid.org/0000-0001-6626-9027</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | The Journal of heart and lung transplantation, 2016-04, Vol.35 (4), p.457-465 |
| issn | 1053-2498 1557-3117 |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Adolescent Child Child, Preschool Female Follow-Up Studies Graft Rejection - drug therapy Graft Rejection - epidemiology Graft Survival Heart Transplantation HMG-CoA reductase inhibitors Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use Incidence Male pediatric heart transplantation PTLD Registries rejection Retrospective Studies Risk Factors statin Surgery Survival Rate - trends Time Factors United Kingdom - epidemiology United States - epidemiology vasculopathy |
| title | Statin therapy is not associated with improved outcomes after heart transplantation in children and adolescents |
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