Long-Term Sirolimus for Primary Immunosuppression in Heart Transplant Recipients
Small studies have reported superiority of sirolimus (SRL) over calcineurin inhibitor (CNI) in mitigating cardiac allograft vasculopathy (CAV) after heart transplantation (HT). However, data on the long-term effect on CAV progression and clinical outcomes are lacking. The aim of this study was to te...
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| Veröffentlicht in: | Journal of the American College of Cardiology 2018-02, Vol.71 (6), p.636-650 |
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| creator | Asleh, Rabea Briasoulis, Alexandros Kremers, Walter K. Adigun, Rosalyn Boilson, Barry A. Pereira, Naveen L. Edwards, Brooks S. Clavell, Alfredo L. Schirger, John A. Rodeheffer, Richard J. Frantz, Robert P. Joyce, Lyle D. Maltais, Simon Stulak, John M. Daly, Richard C. Tilford, Jonella Choi, Woong-Gil Lerman, Amir Kushwaha, Sudhir S. |
| description | Small studies have reported superiority of sirolimus (SRL) over calcineurin inhibitor (CNI) in mitigating cardiac allograft vasculopathy (CAV) after heart transplantation (HT). However, data on the long-term effect on CAV progression and clinical outcomes are lacking.
The aim of this study was to test the long-term safety and efficacy of conversion from CNI to SRL as maintenance therapy on CAV progression and outcomes after HT.
A cohort of 402 patients who underwent HT and were either treated with CNI alone (n = 134) or converted from CNI to SRL (n = 268) as primary immunosuppression was analyzed. CAV progression was assessed using serial coronary intravascular ultrasound during treatment with CNI (n = 99) and after conversion to SRL (n = 235) in patients who underwent at least 2 intravascular ultrasound studies.
The progression in plaque volume (2.8 ± 2.3 mm3/mm vs. 0.46 ± 1.8 mm3/mm; p < 0.0001) and plaque index (plaque volume–to–vessel volume ratio) (12.2 ± 9.6% vs. 1.1 ± 7.9%; p < 0.0001) were significantly attenuated when treated with SRL compared with CNI. Over a mean follow-up period of 8.9 years from time of HT, all-cause mortality occurred in 25.6% of the patients and was lower during treatment with SRL compared with CNI (adjusted hazard ratio: 0.47; 95% confidence interval: 0.31 to 0.70; p = 0.0002), and CAV-related events were also less frequent during treatment with SRL (adjusted hazard ratio: 0.35; 95% confidence interval: 0.21 to 0.59; p < 0.0001). Further analyses suggested more attenuation of CAV and more favorable clinical outcomes with earlier conversion to SRL (≤2 years) compared with late conversion (>2 years) after HT.
Early conversion to SRL is associated with attenuated CAV progression and with lower long-term mortality and fewer CAV-related events compared with continued CNI use.
[Display omitted] |
| doi_str_mv | 10.1016/j.jacc.2017.12.005 |
| format | Article |
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The aim of this study was to test the long-term safety and efficacy of conversion from CNI to SRL as maintenance therapy on CAV progression and outcomes after HT.
A cohort of 402 patients who underwent HT and were either treated with CNI alone (n = 134) or converted from CNI to SRL (n = 268) as primary immunosuppression was analyzed. CAV progression was assessed using serial coronary intravascular ultrasound during treatment with CNI (n = 99) and after conversion to SRL (n = 235) in patients who underwent at least 2 intravascular ultrasound studies.
The progression in plaque volume (2.8 ± 2.3 mm3/mm vs. 0.46 ± 1.8 mm3/mm; p < 0.0001) and plaque index (plaque volume–to–vessel volume ratio) (12.2 ± 9.6% vs. 1.1 ± 7.9%; p < 0.0001) were significantly attenuated when treated with SRL compared with CNI. Over a mean follow-up period of 8.9 years from time of HT, all-cause mortality occurred in 25.6% of the patients and was lower during treatment with SRL compared with CNI (adjusted hazard ratio: 0.47; 95% confidence interval: 0.31 to 0.70; p = 0.0002), and CAV-related events were also less frequent during treatment with SRL (adjusted hazard ratio: 0.35; 95% confidence interval: 0.21 to 0.59; p < 0.0001). Further analyses suggested more attenuation of CAV and more favorable clinical outcomes with earlier conversion to SRL (≤2 years) compared with late conversion (>2 years) after HT.
Early conversion to SRL is associated with attenuated CAV progression and with lower long-term mortality and fewer CAV-related events compared with continued CNI use.
[Display omitted]</description><identifier>ISSN: 0735-1097</identifier><identifier>EISSN: 1558-3597</identifier><identifier>DOI: 10.1016/j.jacc.2017.12.005</identifier><identifier>PMID: 29420960</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adult ; Aged ; Attenuation ; Biopsy ; Calcineurin ; Calcineurin inhibitors ; Calcineurin Inhibitors - administration & dosage ; cardiac allograft vasculopathy ; Cardiology ; Cardiovascular disease ; Cohort Studies ; Confidence intervals ; Conversion ; coronary intravascular ultrasound ; Drug Administration Schedule ; Female ; Follow-Up Studies ; Graft Rejection - immunology ; Graft Rejection - prevention & control ; Health risk assessment ; Heart ; Heart diseases ; Heart transplantation ; Heart Transplantation - trends ; Humans ; Immunosuppression ; Immunosuppressive Agents - administration & dosage ; Laboratories ; Male ; Middle Aged ; Mortality ; Patients ; Plaque index ; Rapamycin ; Retrospective Studies ; Signal transduction ; Sirolimus - administration & dosage ; Smooth muscle ; Time Factors ; Transplant Recipients ; Transplantation ; Transplants & implants ; Ultrasound ; Vascular diseases ; Volumetric analysis ; Wound healing</subject><ispartof>Journal of the American College of Cardiology, 2018-02, Vol.71 (6), p.636-650</ispartof><rights>2018 American College of Cardiology Foundation</rights><rights>Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.</rights><rights>Copyright Elsevier Limited Feb 13, 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c428t-8c0bc359f132449184cd811f27f23f7f3e2bd064d4915ad8a7c8c4a1f3dc436e3</citedby><cites>FETCH-LOGICAL-c428t-8c0bc359f132449184cd811f27f23f7f3e2bd064d4915ad8a7c8c4a1f3dc436e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0735109717418675$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29420960$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Asleh, Rabea</creatorcontrib><creatorcontrib>Briasoulis, Alexandros</creatorcontrib><creatorcontrib>Kremers, Walter K.</creatorcontrib><creatorcontrib>Adigun, Rosalyn</creatorcontrib><creatorcontrib>Boilson, Barry A.</creatorcontrib><creatorcontrib>Pereira, Naveen L.</creatorcontrib><creatorcontrib>Edwards, Brooks S.</creatorcontrib><creatorcontrib>Clavell, Alfredo L.</creatorcontrib><creatorcontrib>Schirger, John A.</creatorcontrib><creatorcontrib>Rodeheffer, Richard J.</creatorcontrib><creatorcontrib>Frantz, Robert P.</creatorcontrib><creatorcontrib>Joyce, Lyle D.</creatorcontrib><creatorcontrib>Maltais, Simon</creatorcontrib><creatorcontrib>Stulak, John M.</creatorcontrib><creatorcontrib>Daly, Richard C.</creatorcontrib><creatorcontrib>Tilford, Jonella</creatorcontrib><creatorcontrib>Choi, Woong-Gil</creatorcontrib><creatorcontrib>Lerman, Amir</creatorcontrib><creatorcontrib>Kushwaha, Sudhir S.</creatorcontrib><title>Long-Term Sirolimus for Primary Immunosuppression in Heart Transplant Recipients</title><title>Journal of the American College of Cardiology</title><addtitle>J Am Coll Cardiol</addtitle><description>Small studies have reported superiority of sirolimus (SRL) over calcineurin inhibitor (CNI) in mitigating cardiac allograft vasculopathy (CAV) after heart transplantation (HT). However, data on the long-term effect on CAV progression and clinical outcomes are lacking.
The aim of this study was to test the long-term safety and efficacy of conversion from CNI to SRL as maintenance therapy on CAV progression and outcomes after HT.
A cohort of 402 patients who underwent HT and were either treated with CNI alone (n = 134) or converted from CNI to SRL (n = 268) as primary immunosuppression was analyzed. CAV progression was assessed using serial coronary intravascular ultrasound during treatment with CNI (n = 99) and after conversion to SRL (n = 235) in patients who underwent at least 2 intravascular ultrasound studies.
The progression in plaque volume (2.8 ± 2.3 mm3/mm vs. 0.46 ± 1.8 mm3/mm; p < 0.0001) and plaque index (plaque volume–to–vessel volume ratio) (12.2 ± 9.6% vs. 1.1 ± 7.9%; p < 0.0001) were significantly attenuated when treated with SRL compared with CNI. Over a mean follow-up period of 8.9 years from time of HT, all-cause mortality occurred in 25.6% of the patients and was lower during treatment with SRL compared with CNI (adjusted hazard ratio: 0.47; 95% confidence interval: 0.31 to 0.70; p = 0.0002), and CAV-related events were also less frequent during treatment with SRL (adjusted hazard ratio: 0.35; 95% confidence interval: 0.21 to 0.59; p < 0.0001). Further analyses suggested more attenuation of CAV and more favorable clinical outcomes with earlier conversion to SRL (≤2 years) compared with late conversion (>2 years) after HT.
Early conversion to SRL is associated with attenuated CAV progression and with lower long-term mortality and fewer CAV-related events compared with continued CNI use.
[Display omitted]</description><subject>Adult</subject><subject>Aged</subject><subject>Attenuation</subject><subject>Biopsy</subject><subject>Calcineurin</subject><subject>Calcineurin inhibitors</subject><subject>Calcineurin Inhibitors - administration & dosage</subject><subject>cardiac allograft vasculopathy</subject><subject>Cardiology</subject><subject>Cardiovascular disease</subject><subject>Cohort Studies</subject><subject>Confidence intervals</subject><subject>Conversion</subject><subject>coronary intravascular ultrasound</subject><subject>Drug Administration Schedule</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Graft Rejection - immunology</subject><subject>Graft Rejection - prevention & control</subject><subject>Health risk assessment</subject><subject>Heart</subject><subject>Heart diseases</subject><subject>Heart transplantation</subject><subject>Heart Transplantation - trends</subject><subject>Humans</subject><subject>Immunosuppression</subject><subject>Immunosuppressive Agents - administration & dosage</subject><subject>Laboratories</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Patients</subject><subject>Plaque index</subject><subject>Rapamycin</subject><subject>Retrospective Studies</subject><subject>Signal transduction</subject><subject>Sirolimus - administration & dosage</subject><subject>Smooth muscle</subject><subject>Time Factors</subject><subject>Transplant Recipients</subject><subject>Transplantation</subject><subject>Transplants & implants</subject><subject>Ultrasound</subject><subject>Vascular diseases</subject><subject>Volumetric analysis</subject><subject>Wound healing</subject><issn>0735-1097</issn><issn>1558-3597</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM9q3DAQh0VJaDZpX6CHYMglFzsz8j8ZeimhyQYWErLbs9DKoyCztlzJDvRt8ix5smi7aQ899DQD882PHx9jXxAyBKyuuqxTWmccsM6QZwDlB7bAshRpXjb1EVtAnZcpQlOfsNMQOgCoBDYf2QlvCg5NBQu2XrnhKd2Q75O19W5n-zkkxvnkwdte-V-vL3d9Pw8uzOPoKQTrhsQOyZKUn15fNl4NYdypIe6PpO1oaZjCJ3Zs1C7Q5_d5xn7cfN9cL9PV_e3d9bdVqgsuplRo2OrY1GDOi6JBUehWIBpeG56b2uTEty1URRtvpWqFqrXQhUKTt7rIK8rP2OUhd_Tu50xhkr0NmnaxD7k5SA6AUFVNIyJ68Q_audkPsd1vqkRRAo8UP1DauxA8GTkeLEgEuVcuO7lXLvfKJXIZlcen8_foedtT-_flj-MIfD0AFF08W_Iy6OhJU2s96Um2zv4v_w1Z35Rp</recordid><startdate>20180213</startdate><enddate>20180213</enddate><creator>Asleh, Rabea</creator><creator>Briasoulis, Alexandros</creator><creator>Kremers, Walter K.</creator><creator>Adigun, Rosalyn</creator><creator>Boilson, Barry A.</creator><creator>Pereira, Naveen L.</creator><creator>Edwards, Brooks S.</creator><creator>Clavell, Alfredo L.</creator><creator>Schirger, John A.</creator><creator>Rodeheffer, Richard J.</creator><creator>Frantz, Robert P.</creator><creator>Joyce, Lyle D.</creator><creator>Maltais, Simon</creator><creator>Stulak, John M.</creator><creator>Daly, Richard C.</creator><creator>Tilford, Jonella</creator><creator>Choi, Woong-Gil</creator><creator>Lerman, Amir</creator><creator>Kushwaha, Sudhir S.</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><scope>6I.</scope><scope>AAFTH</scope><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>7T5</scope><scope>7TK</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>20180213</creationdate><title>Long-Term Sirolimus for Primary Immunosuppression in Heart Transplant Recipients</title><author>Asleh, Rabea ; Briasoulis, Alexandros ; Kremers, Walter K. ; Adigun, Rosalyn ; Boilson, Barry A. ; Pereira, Naveen L. ; Edwards, Brooks S. ; Clavell, Alfredo L. ; Schirger, John A. ; Rodeheffer, Richard J. ; Frantz, Robert P. ; Joyce, Lyle D. ; Maltais, Simon ; Stulak, John M. ; Daly, Richard C. ; Tilford, Jonella ; Choi, Woong-Gil ; Lerman, Amir ; Kushwaha, Sudhir S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c428t-8c0bc359f132449184cd811f27f23f7f3e2bd064d4915ad8a7c8c4a1f3dc436e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Attenuation</topic><topic>Biopsy</topic><topic>Calcineurin</topic><topic>Calcineurin inhibitors</topic><topic>Calcineurin Inhibitors - administration & dosage</topic><topic>cardiac allograft vasculopathy</topic><topic>Cardiology</topic><topic>Cardiovascular disease</topic><topic>Cohort Studies</topic><topic>Confidence intervals</topic><topic>Conversion</topic><topic>coronary intravascular ultrasound</topic><topic>Drug Administration Schedule</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Graft Rejection - immunology</topic><topic>Graft Rejection - prevention & control</topic><topic>Health risk assessment</topic><topic>Heart</topic><topic>Heart diseases</topic><topic>Heart transplantation</topic><topic>Heart Transplantation - trends</topic><topic>Humans</topic><topic>Immunosuppression</topic><topic>Immunosuppressive Agents - administration & dosage</topic><topic>Laboratories</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Mortality</topic><topic>Patients</topic><topic>Plaque index</topic><topic>Rapamycin</topic><topic>Retrospective Studies</topic><topic>Signal transduction</topic><topic>Sirolimus - administration & dosage</topic><topic>Smooth muscle</topic><topic>Time Factors</topic><topic>Transplant Recipients</topic><topic>Transplantation</topic><topic>Transplants & implants</topic><topic>Ultrasound</topic><topic>Vascular diseases</topic><topic>Volumetric analysis</topic><topic>Wound healing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Asleh, Rabea</creatorcontrib><creatorcontrib>Briasoulis, Alexandros</creatorcontrib><creatorcontrib>Kremers, Walter K.</creatorcontrib><creatorcontrib>Adigun, Rosalyn</creatorcontrib><creatorcontrib>Boilson, Barry A.</creatorcontrib><creatorcontrib>Pereira, Naveen L.</creatorcontrib><creatorcontrib>Edwards, Brooks S.</creatorcontrib><creatorcontrib>Clavell, Alfredo L.</creatorcontrib><creatorcontrib>Schirger, John A.</creatorcontrib><creatorcontrib>Rodeheffer, Richard J.</creatorcontrib><creatorcontrib>Frantz, Robert P.</creatorcontrib><creatorcontrib>Joyce, Lyle D.</creatorcontrib><creatorcontrib>Maltais, Simon</creatorcontrib><creatorcontrib>Stulak, John M.</creatorcontrib><creatorcontrib>Daly, Richard C.</creatorcontrib><creatorcontrib>Tilford, Jonella</creatorcontrib><creatorcontrib>Choi, Woong-Gil</creatorcontrib><creatorcontrib>Lerman, Amir</creatorcontrib><creatorcontrib>Kushwaha, Sudhir S.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</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>Asleh, Rabea</au><au>Briasoulis, Alexandros</au><au>Kremers, Walter K.</au><au>Adigun, Rosalyn</au><au>Boilson, Barry A.</au><au>Pereira, Naveen L.</au><au>Edwards, Brooks S.</au><au>Clavell, Alfredo L.</au><au>Schirger, John A.</au><au>Rodeheffer, Richard J.</au><au>Frantz, Robert P.</au><au>Joyce, Lyle D.</au><au>Maltais, Simon</au><au>Stulak, John M.</au><au>Daly, Richard C.</au><au>Tilford, Jonella</au><au>Choi, Woong-Gil</au><au>Lerman, Amir</au><au>Kushwaha, Sudhir S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Long-Term Sirolimus for Primary Immunosuppression in Heart Transplant Recipients</atitle><jtitle>Journal of the American College of Cardiology</jtitle><addtitle>J Am Coll Cardiol</addtitle><date>2018-02-13</date><risdate>2018</risdate><volume>71</volume><issue>6</issue><spage>636</spage><epage>650</epage><pages>636-650</pages><issn>0735-1097</issn><eissn>1558-3597</eissn><abstract>Small studies have reported superiority of sirolimus (SRL) over calcineurin inhibitor (CNI) in mitigating cardiac allograft vasculopathy (CAV) after heart transplantation (HT). However, data on the long-term effect on CAV progression and clinical outcomes are lacking.
The aim of this study was to test the long-term safety and efficacy of conversion from CNI to SRL as maintenance therapy on CAV progression and outcomes after HT.
A cohort of 402 patients who underwent HT and were either treated with CNI alone (n = 134) or converted from CNI to SRL (n = 268) as primary immunosuppression was analyzed. CAV progression was assessed using serial coronary intravascular ultrasound during treatment with CNI (n = 99) and after conversion to SRL (n = 235) in patients who underwent at least 2 intravascular ultrasound studies.
The progression in plaque volume (2.8 ± 2.3 mm3/mm vs. 0.46 ± 1.8 mm3/mm; p < 0.0001) and plaque index (plaque volume–to–vessel volume ratio) (12.2 ± 9.6% vs. 1.1 ± 7.9%; p < 0.0001) were significantly attenuated when treated with SRL compared with CNI. Over a mean follow-up period of 8.9 years from time of HT, all-cause mortality occurred in 25.6% of the patients and was lower during treatment with SRL compared with CNI (adjusted hazard ratio: 0.47; 95% confidence interval: 0.31 to 0.70; p = 0.0002), and CAV-related events were also less frequent during treatment with SRL (adjusted hazard ratio: 0.35; 95% confidence interval: 0.21 to 0.59; p < 0.0001). Further analyses suggested more attenuation of CAV and more favorable clinical outcomes with earlier conversion to SRL (≤2 years) compared with late conversion (>2 years) after HT.
Early conversion to SRL is associated with attenuated CAV progression and with lower long-term mortality and fewer CAV-related events compared with continued CNI use.
[Display omitted]</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>29420960</pmid><doi>10.1016/j.jacc.2017.12.005</doi><tpages>15</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 | Adult Aged Attenuation Biopsy Calcineurin Calcineurin inhibitors Calcineurin Inhibitors - administration & dosage cardiac allograft vasculopathy Cardiology Cardiovascular disease Cohort Studies Confidence intervals Conversion coronary intravascular ultrasound Drug Administration Schedule Female Follow-Up Studies Graft Rejection - immunology Graft Rejection - prevention & control Health risk assessment Heart Heart diseases Heart transplantation Heart Transplantation - trends Humans Immunosuppression Immunosuppressive Agents - administration & dosage Laboratories Male Middle Aged Mortality Patients Plaque index Rapamycin Retrospective Studies Signal transduction Sirolimus - administration & dosage Smooth muscle Time Factors Transplant Recipients Transplantation Transplants & implants Ultrasound Vascular diseases Volumetric analysis Wound healing |
| title | Long-Term Sirolimus for Primary Immunosuppression in Heart Transplant Recipients |
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