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Rapid and high-dose titration of epoprostenol improves pulmonary hemodynamics and clinical outcomes in patients with idiopathic and heritable pulmonary arterial hypertension
Abstract Background Intravenous epoprostenol is an effective treatment for idiopathic and heritable pulmonary arterial hypertension. We aimed to clarify factors that determine the survival of patients with severe pulmonary hypertension who received epoprostenol treatment. Methods This is a retrospec...
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Published in: | Journal of cardiology 2016-12, Vol.68 (6), p.542-547 |
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description | Abstract Background Intravenous epoprostenol is an effective treatment for idiopathic and heritable pulmonary arterial hypertension. We aimed to clarify factors that determine the survival of patients with severe pulmonary hypertension who received epoprostenol treatment. Methods This is a retrospective observational study consisting of 46 patients with idiopathic and heritable pulmonary arterial hypertension in World Health Organization (WHO) functional class III or IV and undergoing intravenous epoprostenol treatment. We compared the following factors between survivors and non-survivors: clinical characteristics, exercise capacity, hemodynamics, interval between diagnosis and treatment initiation, concomitant pulmonary arterial hypertension-targeted drugs, maximum dose of epoprostenol, and the speed of up-titration. We defined a rapid increase group as those receiving epoprostenol ≥20 ng/kg/min at 3 months and ≥45 ng/kg/min at 1 year of treatment. Results Thirty-two patients (70%) survived and 14 patients died during an average follow-up period of 2100 days. Mean pulmonary artery pressure, concomitant pulmonary arterial hypertension-targeted drugs, and the maximum epoprostenol dose were comparable between the two subsets of patients. WHO functional class III was more common than class IV, and the 6-min walking distance was longer in the survivor than the non-survivor group. The survivors typically showed a rapid increase in epoprostenol dose during the first year of treatment. This rapid increase group was associated with a continuous reduction in mean pulmonary artery pressure during the follow-up period, whereas the slow increase group showed no reduction in mean pulmonary artery pressure after 6 months of treatment. The 9.5-year survival rate was also significantly better in the rapid increase group compared with the slow increase group (100% vs. 64%, p = 0.022). Conclusions In idiopathic and heritable pulmonary arterial hypertension patients, a rapid increase in epoprostenol dose soon after the initiation of treatment seems to be important to achieve a continuous reduction in mean pulmonary artery pressure and to improve survival. |
doi_str_mv | 10.1016/j.jjcc.2015.11.012 |
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We aimed to clarify factors that determine the survival of patients with severe pulmonary hypertension who received epoprostenol treatment. Methods This is a retrospective observational study consisting of 46 patients with idiopathic and heritable pulmonary arterial hypertension in World Health Organization (WHO) functional class III or IV and undergoing intravenous epoprostenol treatment. We compared the following factors between survivors and non-survivors: clinical characteristics, exercise capacity, hemodynamics, interval between diagnosis and treatment initiation, concomitant pulmonary arterial hypertension-targeted drugs, maximum dose of epoprostenol, and the speed of up-titration. We defined a rapid increase group as those receiving epoprostenol ≥20 ng/kg/min at 3 months and ≥45 ng/kg/min at 1 year of treatment. Results Thirty-two patients (70%) survived and 14 patients died during an average follow-up period of 2100 days. Mean pulmonary artery pressure, concomitant pulmonary arterial hypertension-targeted drugs, and the maximum epoprostenol dose were comparable between the two subsets of patients. WHO functional class III was more common than class IV, and the 6-min walking distance was longer in the survivor than the non-survivor group. The survivors typically showed a rapid increase in epoprostenol dose during the first year of treatment. This rapid increase group was associated with a continuous reduction in mean pulmonary artery pressure during the follow-up period, whereas the slow increase group showed no reduction in mean pulmonary artery pressure after 6 months of treatment. The 9.5-year survival rate was also significantly better in the rapid increase group compared with the slow increase group (100% vs. 64%, p = 0.022). Conclusions In idiopathic and heritable pulmonary arterial hypertension patients, a rapid increase in epoprostenol dose soon after the initiation of treatment seems to be important to achieve a continuous reduction in mean pulmonary artery pressure and to improve survival.</description><identifier>ISSN: 0914-5087</identifier><identifier>EISSN: 1876-4738</identifier><identifier>DOI: 10.1016/j.jjcc.2015.11.012</identifier><identifier>PMID: 27005767</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Adult ; Antihypertensive Agents - administration & dosage ; Cardiovascular ; Dose titration ; Dose-Response Relationship, Drug ; Epoprostenol ; Epoprostenol - administration & dosage ; Familial Primary Pulmonary Hypertension - drug therapy ; Familial Primary Pulmonary Hypertension - mortality ; Female ; Follow-Up Studies ; Humans ; Infusions, Intravenous ; Male ; Pulmonary arterial hypertension ; Pulmonary artery pressure ; Retrospective Studies ; Survival ; Walk Test</subject><ispartof>Journal of cardiology, 2016-12, Vol.68 (6), p.542-547</ispartof><rights>Japanese College of Cardiology</rights><rights>2015 Japanese College of Cardiology</rights><rights>Copyright © 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c479t-e1f877238b27d5b35414e797c80dcab02f21c6a05510c61e1b608a7f56e2f15f3</citedby><cites>FETCH-LOGICAL-c479t-e1f877238b27d5b35414e797c80dcab02f21c6a05510c61e1b608a7f56e2f15f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27005767$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tokunaga, Naoto, MD</creatorcontrib><creatorcontrib>Ogawa, Aiko, MD, PhD</creatorcontrib><creatorcontrib>Ito, Hiroshi, MD, PhD, FJCC</creatorcontrib><creatorcontrib>Matsubara, Hiromi, MD, PhD</creatorcontrib><title>Rapid and high-dose titration of epoprostenol improves pulmonary hemodynamics and clinical outcomes in patients with idiopathic and heritable pulmonary arterial hypertension</title><title>Journal of cardiology</title><addtitle>J Cardiol</addtitle><description>Abstract Background Intravenous epoprostenol is an effective treatment for idiopathic and heritable pulmonary arterial hypertension. We aimed to clarify factors that determine the survival of patients with severe pulmonary hypertension who received epoprostenol treatment. Methods This is a retrospective observational study consisting of 46 patients with idiopathic and heritable pulmonary arterial hypertension in World Health Organization (WHO) functional class III or IV and undergoing intravenous epoprostenol treatment. We compared the following factors between survivors and non-survivors: clinical characteristics, exercise capacity, hemodynamics, interval between diagnosis and treatment initiation, concomitant pulmonary arterial hypertension-targeted drugs, maximum dose of epoprostenol, and the speed of up-titration. We defined a rapid increase group as those receiving epoprostenol ≥20 ng/kg/min at 3 months and ≥45 ng/kg/min at 1 year of treatment. Results Thirty-two patients (70%) survived and 14 patients died during an average follow-up period of 2100 days. Mean pulmonary artery pressure, concomitant pulmonary arterial hypertension-targeted drugs, and the maximum epoprostenol dose were comparable between the two subsets of patients. WHO functional class III was more common than class IV, and the 6-min walking distance was longer in the survivor than the non-survivor group. The survivors typically showed a rapid increase in epoprostenol dose during the first year of treatment. This rapid increase group was associated with a continuous reduction in mean pulmonary artery pressure during the follow-up period, whereas the slow increase group showed no reduction in mean pulmonary artery pressure after 6 months of treatment. The 9.5-year survival rate was also significantly better in the rapid increase group compared with the slow increase group (100% vs. 64%, p = 0.022). Conclusions In idiopathic and heritable pulmonary arterial hypertension patients, a rapid increase in epoprostenol dose soon after the initiation of treatment seems to be important to achieve a continuous reduction in mean pulmonary artery pressure and to improve survival.</description><subject>Adult</subject><subject>Antihypertensive Agents - administration & dosage</subject><subject>Cardiovascular</subject><subject>Dose titration</subject><subject>Dose-Response Relationship, Drug</subject><subject>Epoprostenol</subject><subject>Epoprostenol - administration & dosage</subject><subject>Familial Primary Pulmonary Hypertension - drug therapy</subject><subject>Familial Primary Pulmonary Hypertension - mortality</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Humans</subject><subject>Infusions, Intravenous</subject><subject>Male</subject><subject>Pulmonary arterial hypertension</subject><subject>Pulmonary artery pressure</subject><subject>Retrospective Studies</subject><subject>Survival</subject><subject>Walk Test</subject><issn>0914-5087</issn><issn>1876-4738</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><recordid>eNp9kt-K1TAQxoso7tnVF_BCculNayZtkxZEkEVdYUHwz3VIk6lNbZPapLuch_IdTT27Il54NcPwzS-Z-SbLngEtgAJ_ORbjqHXBKNQFQEGBPcgO0AieV6JsHmYH2kKV17QRZ9l5CCOlnLYNf5ydMUFpLbg4ZD8_qcUaopwhg_025MYHJNHGVUXrHfE9wcUvqw8RnZ-InVN-g4Es2zR7p9YjGXD25ujUbHX4zdGTdVarifgtaj8nsXVkSTx0MZBbGwdijfWpMlh9ehlXG1U34V9YtcZUTZThuGDKXUj_eZI96tUU8OldvMi-vnv75fIqv_74_sPlm-tcV6KNOULfCMHKpmPC1F1ZV1ChaIVuqNGqo6xnoLmidQ1Uc0DoOG2U6GuOrIe6Ly-yFydumvbHhiHK2QaN06Qc-i1IaBjnvK1KnqTsJNVpSWHFXi6rndMEEqjcbZKj3G2Su00SQCabUtPzO_7WzWj-tNz7kgSvTgJMU95YXGXQaX8ajV1RR2m8_T__9T_t96Z8xyOG0W-rS_uTIAOTVH7eD2W_E6gpLVMofwH10L3P</recordid><startdate>20161201</startdate><enddate>20161201</enddate><creator>Tokunaga, Naoto, MD</creator><creator>Ogawa, Aiko, MD, PhD</creator><creator>Ito, Hiroshi, MD, PhD, FJCC</creator><creator>Matsubara, Hiromi, MD, PhD</creator><general>Elsevier Ltd</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>7X8</scope></search><sort><creationdate>20161201</creationdate><title>Rapid and high-dose titration of epoprostenol improves pulmonary hemodynamics and clinical outcomes in patients with idiopathic and heritable pulmonary arterial hypertension</title><author>Tokunaga, Naoto, MD ; Ogawa, Aiko, MD, PhD ; Ito, Hiroshi, MD, PhD, FJCC ; Matsubara, Hiromi, MD, PhD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c479t-e1f877238b27d5b35414e797c80dcab02f21c6a05510c61e1b608a7f56e2f15f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Antihypertensive Agents - administration & dosage</topic><topic>Cardiovascular</topic><topic>Dose titration</topic><topic>Dose-Response Relationship, Drug</topic><topic>Epoprostenol</topic><topic>Epoprostenol - administration & dosage</topic><topic>Familial Primary Pulmonary Hypertension - drug therapy</topic><topic>Familial Primary Pulmonary Hypertension - mortality</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Humans</topic><topic>Infusions, Intravenous</topic><topic>Male</topic><topic>Pulmonary arterial hypertension</topic><topic>Pulmonary artery pressure</topic><topic>Retrospective Studies</topic><topic>Survival</topic><topic>Walk Test</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tokunaga, Naoto, MD</creatorcontrib><creatorcontrib>Ogawa, Aiko, MD, PhD</creatorcontrib><creatorcontrib>Ito, Hiroshi, MD, PhD, FJCC</creatorcontrib><creatorcontrib>Matsubara, Hiromi, MD, PhD</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>MEDLINE - Academic</collection><jtitle>Journal of cardiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tokunaga, Naoto, MD</au><au>Ogawa, Aiko, MD, PhD</au><au>Ito, Hiroshi, MD, PhD, FJCC</au><au>Matsubara, Hiromi, MD, PhD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Rapid and high-dose titration of epoprostenol improves pulmonary hemodynamics and clinical outcomes in patients with idiopathic and heritable pulmonary arterial hypertension</atitle><jtitle>Journal of cardiology</jtitle><addtitle>J Cardiol</addtitle><date>2016-12-01</date><risdate>2016</risdate><volume>68</volume><issue>6</issue><spage>542</spage><epage>547</epage><pages>542-547</pages><issn>0914-5087</issn><eissn>1876-4738</eissn><abstract>Abstract Background Intravenous epoprostenol is an effective treatment for idiopathic and heritable pulmonary arterial hypertension. We aimed to clarify factors that determine the survival of patients with severe pulmonary hypertension who received epoprostenol treatment. Methods This is a retrospective observational study consisting of 46 patients with idiopathic and heritable pulmonary arterial hypertension in World Health Organization (WHO) functional class III or IV and undergoing intravenous epoprostenol treatment. We compared the following factors between survivors and non-survivors: clinical characteristics, exercise capacity, hemodynamics, interval between diagnosis and treatment initiation, concomitant pulmonary arterial hypertension-targeted drugs, maximum dose of epoprostenol, and the speed of up-titration. We defined a rapid increase group as those receiving epoprostenol ≥20 ng/kg/min at 3 months and ≥45 ng/kg/min at 1 year of treatment. Results Thirty-two patients (70%) survived and 14 patients died during an average follow-up period of 2100 days. Mean pulmonary artery pressure, concomitant pulmonary arterial hypertension-targeted drugs, and the maximum epoprostenol dose were comparable between the two subsets of patients. WHO functional class III was more common than class IV, and the 6-min walking distance was longer in the survivor than the non-survivor group. The survivors typically showed a rapid increase in epoprostenol dose during the first year of treatment. This rapid increase group was associated with a continuous reduction in mean pulmonary artery pressure during the follow-up period, whereas the slow increase group showed no reduction in mean pulmonary artery pressure after 6 months of treatment. The 9.5-year survival rate was also significantly better in the rapid increase group compared with the slow increase group (100% vs. 64%, p = 0.022). Conclusions In idiopathic and heritable pulmonary arterial hypertension patients, a rapid increase in epoprostenol dose soon after the initiation of treatment seems to be important to achieve a continuous reduction in mean pulmonary artery pressure and to improve survival.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>27005767</pmid><doi>10.1016/j.jjcc.2015.11.012</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adult Antihypertensive Agents - administration & dosage Cardiovascular Dose titration Dose-Response Relationship, Drug Epoprostenol Epoprostenol - administration & dosage Familial Primary Pulmonary Hypertension - drug therapy Familial Primary Pulmonary Hypertension - mortality Female Follow-Up Studies Humans Infusions, Intravenous Male Pulmonary arterial hypertension Pulmonary artery pressure Retrospective Studies Survival Walk Test |
title | Rapid and high-dose titration of epoprostenol improves pulmonary hemodynamics and clinical outcomes in patients with idiopathic and heritable pulmonary arterial hypertension |
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