Topiroxostat versus allopurinol in patients with chronic heart failure complicated by hyperuricemia: A prospective, randomized, open-label, blinded-end-point clinical trial
The benefits of xanthine oxidase inhibitors to chronic heart failure (CHF) patients is controversial. We investigated the beneficial effects of a novel xanthine oxidoreductase inhibitor, topiroxostat, in patients with CHF and hyperuricemia (HU), in comparison to allopurinol. The prospective, randomi...
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| Veröffentlicht in: | PloS one 2022-01, Vol.17 (1), p.e0261445-e0261445 |
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| creator | Sakuma, Masashi Toyoda, Shigeru Arikawa, Takuo Koyabu, Yota Kato, Toru Adachi, Taichi Suwa, Hideaki Narita, Jun-Ichi Anraku, Koetsu Ishimura, Kimihiko Yamauchi, Fumitake Sato, Yasunori Inoue, Teruo |
| description | The benefits of xanthine oxidase inhibitors to chronic heart failure (CHF) patients is controversial. We investigated the beneficial effects of a novel xanthine oxidoreductase inhibitor, topiroxostat, in patients with CHF and hyperuricemia (HU), in comparison to allopurinol.
The prospective, randomized open-label, blinded-end-point study was performed in 141 patients with CHF and HU at 4 centers. Patients were randomly assigned to either topiroxostat or allopurinol group to achieve target uric acid level ≤6.0 mg/dL. According to the protocol, 140 patients were followed up for 24 weeks. Percent change in ln (N-terminal-proB-type natriuretic peptide) at week 24 (primary endpoint) was comparable between topiroxostat and allopurinol groups (1.6±8.2 versus -0.4±8.0%; P = 0.17). In the limited number of patients with heart failure with reduced ejection fraction (HFrEF) (left ventricle ejection fraction |
| doi_str_mv | 10.1371/journal.pone.0261445 |
| format | Article |
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The prospective, randomized open-label, blinded-end-point study was performed in 141 patients with CHF and HU at 4 centers. Patients were randomly assigned to either topiroxostat or allopurinol group to achieve target uric acid level ≤6.0 mg/dL. According to the protocol, 140 patients were followed up for 24 weeks. Percent change in ln (N-terminal-proB-type natriuretic peptide) at week 24 (primary endpoint) was comparable between topiroxostat and allopurinol groups (1.6±8.2 versus -0.4±8.0%; P = 0.17). In the limited number of patients with heart failure with reduced ejection fraction (HFrEF) (left ventricle ejection fraction <45%), ratio of peak early diastolic flow velocity at mitral valve leaflet to early diastolic mitral annular motion velocity (E/e') decreased in topiroxostat group, but not in allopurinol group. Urinary 8-hydroxy-2'-deoxyguanosine and L-type fatty acid-binding protein levels increased and osmolality decreased significantly in allopurinol group, while these changes were less or absent in topiroxostat group. In allopurinol group HFrEF patients, additional to the increases in these urinary marker levels, urinary creatinine levels decreased, with no change in clearance, but not in topiroxostat group.
Compared with allopurinol, topiroxostat did not show great benefits in patients with CHF and HU. However, topiroxostat might have potential advantages of reducing left ventricular end-diastolic pressure, not worsening oxidative stress in proximal renal tubule, and renoprotection over allopurinol in HFrEF patients.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0261445</identifier><identifier>PMID: 35077456</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aged ; Aged, 80 and over ; Allopurinol ; Allopurinol - administration & dosage ; Allopurinol - therapeutic use ; Biology and Life Sciences ; Biomarkers ; Biomarkers - urine ; Blood pressure ; Cardiology ; Care and treatment ; Clinical trials ; Comparative analysis ; Congestive heart failure ; Creatinine ; Deoxyguanosine ; Diastolic pressure ; Drug dosages ; Drug therapy ; Enzyme inhibitors ; Ethics ; Fatty acid-binding protein ; Fatty acids ; Female ; Flow velocity ; Gout ; Health care ; Heart failure ; Heart Failure - complications ; Heart Failure - drug therapy ; Heart Failure - metabolism ; Heart Failure - physiopathology ; Heart valves ; Hospitals ; Humans ; Hypertension ; Hyperuricemia ; Hyperuricemia - drug therapy ; Hyperuricemia - etiology ; Hyperuricemia - metabolism ; Hyperuricemia - physiopathology ; Internal medicine ; Male ; Medicine and Health Sciences ; Middle Aged ; Mitral valve ; Mortality ; Natriuretic Peptide, Brain - metabolism ; Nitriles - administration & dosage ; Nitriles - therapeutic use ; Oxidative stress ; Oxidoreductase ; Patients ; Peptide Fragments - metabolism ; Peptides ; Physical Sciences ; Preventive medicine ; Prospective Studies ; Pyridines - administration & dosage ; Pyridines - therapeutic use ; Research and Analysis Methods ; Rheumatism ; Stroke Volume - drug effects ; Testing ; Treatment Outcome ; Uric acid ; Valve leaflets ; Velocity ; Ventricle ; Xanthine oxidase ; Xanthine oxidoreductase</subject><ispartof>PloS one, 2022-01, Vol.17 (1), p.e0261445-e0261445</ispartof><rights>COPYRIGHT 2022 Public Library of Science</rights><rights>2022 Sakuma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 Sakuma et al 2022 Sakuma et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6075-a1c502cef1312bb1aeed32321538f0fd1619e277dcecdfa49434b39473f2375c3</citedby><cites>FETCH-LOGICAL-c6075-a1c502cef1312bb1aeed32321538f0fd1619e277dcecdfa49434b39473f2375c3</cites><orcidid>0000-0002-3892-0799</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8789120/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8789120/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35077456$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sakuma, Masashi</creatorcontrib><creatorcontrib>Toyoda, Shigeru</creatorcontrib><creatorcontrib>Arikawa, Takuo</creatorcontrib><creatorcontrib>Koyabu, Yota</creatorcontrib><creatorcontrib>Kato, Toru</creatorcontrib><creatorcontrib>Adachi, Taichi</creatorcontrib><creatorcontrib>Suwa, Hideaki</creatorcontrib><creatorcontrib>Narita, Jun-Ichi</creatorcontrib><creatorcontrib>Anraku, Koetsu</creatorcontrib><creatorcontrib>Ishimura, Kimihiko</creatorcontrib><creatorcontrib>Yamauchi, Fumitake</creatorcontrib><creatorcontrib>Sato, Yasunori</creatorcontrib><creatorcontrib>Inoue, Teruo</creatorcontrib><title>Topiroxostat versus allopurinol in patients with chronic heart failure complicated by hyperuricemia: A prospective, randomized, open-label, blinded-end-point clinical trial</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The benefits of xanthine oxidase inhibitors to chronic heart failure (CHF) patients is controversial. We investigated the beneficial effects of a novel xanthine oxidoreductase inhibitor, topiroxostat, in patients with CHF and hyperuricemia (HU), in comparison to allopurinol.
The prospective, randomized open-label, blinded-end-point study was performed in 141 patients with CHF and HU at 4 centers. Patients were randomly assigned to either topiroxostat or allopurinol group to achieve target uric acid level ≤6.0 mg/dL. According to the protocol, 140 patients were followed up for 24 weeks. Percent change in ln (N-terminal-proB-type natriuretic peptide) at week 24 (primary endpoint) was comparable between topiroxostat and allopurinol groups (1.6±8.2 versus -0.4±8.0%; P = 0.17). In the limited number of patients with heart failure with reduced ejection fraction (HFrEF) (left ventricle ejection fraction <45%), ratio of peak early diastolic flow velocity at mitral valve leaflet to early diastolic mitral annular motion velocity (E/e') decreased in topiroxostat group, but not in allopurinol group. Urinary 8-hydroxy-2'-deoxyguanosine and L-type fatty acid-binding protein levels increased and osmolality decreased significantly in allopurinol group, while these changes were less or absent in topiroxostat group. In allopurinol group HFrEF patients, additional to the increases in these urinary marker levels, urinary creatinine levels decreased, with no change in clearance, but not in topiroxostat group.
Compared with allopurinol, topiroxostat did not show great benefits in patients with CHF and HU. However, topiroxostat might have potential advantages of reducing left ventricular end-diastolic pressure, not worsening oxidative stress in proximal renal tubule, and renoprotection over allopurinol in HFrEF patients.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Allopurinol</subject><subject>Allopurinol - administration & dosage</subject><subject>Allopurinol - therapeutic use</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers</subject><subject>Biomarkers - urine</subject><subject>Blood pressure</subject><subject>Cardiology</subject><subject>Care and treatment</subject><subject>Clinical trials</subject><subject>Comparative analysis</subject><subject>Congestive heart failure</subject><subject>Creatinine</subject><subject>Deoxyguanosine</subject><subject>Diastolic pressure</subject><subject>Drug dosages</subject><subject>Drug therapy</subject><subject>Enzyme inhibitors</subject><subject>Ethics</subject><subject>Fatty acid-binding protein</subject><subject>Fatty acids</subject><subject>Female</subject><subject>Flow velocity</subject><subject>Gout</subject><subject>Health care</subject><subject>Heart failure</subject><subject>Heart Failure - complications</subject><subject>Heart Failure - drug therapy</subject><subject>Heart Failure - metabolism</subject><subject>Heart Failure - physiopathology</subject><subject>Heart valves</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Hyperuricemia</subject><subject>Hyperuricemia - drug therapy</subject><subject>Hyperuricemia - etiology</subject><subject>Hyperuricemia - metabolism</subject><subject>Hyperuricemia - physiopathology</subject><subject>Internal medicine</subject><subject>Male</subject><subject>Medicine and Health Sciences</subject><subject>Middle Aged</subject><subject>Mitral valve</subject><subject>Mortality</subject><subject>Natriuretic Peptide, Brain - metabolism</subject><subject>Nitriles - administration & dosage</subject><subject>Nitriles - therapeutic use</subject><subject>Oxidative stress</subject><subject>Oxidoreductase</subject><subject>Patients</subject><subject>Peptide Fragments - metabolism</subject><subject>Peptides</subject><subject>Physical Sciences</subject><subject>Preventive medicine</subject><subject>Prospective Studies</subject><subject>Pyridines - administration & dosage</subject><subject>Pyridines - therapeutic use</subject><subject>Research and Analysis Methods</subject><subject>Rheumatism</subject><subject>Stroke Volume - drug effects</subject><subject>Testing</subject><subject>Treatment Outcome</subject><subject>Uric acid</subject><subject>Valve leaflets</subject><subject>Velocity</subject><subject>Ventricle</subject><subject>Xanthine oxidase</subject><subject>Xanthine oxidoreductase</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk11rFDEUhgdRbK3-A9GAIAo76ySZSXa8EJbiR6FQ0OptyCRndlOyyTTJrF1_kz_S1N2WrvRC5mKGM8_7JuerKJ7jaoopx-8u_BictNPBO5hWhOG6bh4Uh7ilpGSkog_vfB8UT2K8qKqGzhh7XBzQpuK8bthh8fvcDyb4Kx-TTGgNIY4RSWv9MAbjvEXGoUEmAy5F9NOkJVLL4J1RaAkyJNRLY8cASPnVYI2SCTTqNmi5GSBkBwUrI9-jORqCjwOoZNYwQUE67VfmF-gJ8gO40soO7AR11jgNugSny8Ebl5DKkexqUQpG2qfFo17aCM9276Pi-6eP58dfytOzzyfH89NSsYo3pcSqqYiCHlNMug5LAE0JJTin31e9xgy3QDjXCpTuZd3WtO5oW3PaE8obRY-Kl1vfwfoodoWOgjCSVZgxmomTLaG9vBBDMCsZNsJLI_4GfFiIXB2jLAiiZF9JqThTvJ4xPOtbrDFgTlgHwHX2-rA7bexWkC_lUpB2z3T_jzNLsfBrMeOzFufuHhVvdgbBX44Qk1iZqMBa6cCP23u3jOKmzuirf9D7s9tRC5kTMK73-Vx1bSrmrK1q2s5ok6npPVR-dG66ylPZmxzfE7zdE2QmwVVayDFGcfLt6_-zZz_22dd32DyXNi2jt2My3sV9sN6CKk9jDNDfFhlX4nqpbqohrpdK7JYqy17cbdCt6GaL6B-c6yDS</recordid><startdate>20220125</startdate><enddate>20220125</enddate><creator>Sakuma, Masashi</creator><creator>Toyoda, Shigeru</creator><creator>Arikawa, Takuo</creator><creator>Koyabu, Yota</creator><creator>Kato, Toru</creator><creator>Adachi, Taichi</creator><creator>Suwa, Hideaki</creator><creator>Narita, Jun-Ichi</creator><creator>Anraku, Koetsu</creator><creator>Ishimura, Kimihiko</creator><creator>Yamauchi, Fumitake</creator><creator>Sato, Yasunori</creator><creator>Inoue, Teruo</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-3892-0799</orcidid></search><sort><creationdate>20220125</creationdate><title>Topiroxostat versus allopurinol in patients with chronic heart failure complicated by hyperuricemia: A prospective, randomized, open-label, blinded-end-point clinical trial</title><author>Sakuma, Masashi ; Toyoda, Shigeru ; Arikawa, Takuo ; Koyabu, Yota ; Kato, Toru ; Adachi, Taichi ; Suwa, Hideaki ; Narita, Jun-Ichi ; Anraku, Koetsu ; Ishimura, Kimihiko ; Yamauchi, Fumitake ; Sato, Yasunori ; Inoue, Teruo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6075-a1c502cef1312bb1aeed32321538f0fd1619e277dcecdfa49434b39473f2375c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Allopurinol</topic><topic>Allopurinol - administration & dosage</topic><topic>Allopurinol - therapeutic use</topic><topic>Biology and Life Sciences</topic><topic>Biomarkers</topic><topic>Biomarkers - urine</topic><topic>Blood pressure</topic><topic>Cardiology</topic><topic>Care and treatment</topic><topic>Clinical trials</topic><topic>Comparative analysis</topic><topic>Congestive heart failure</topic><topic>Creatinine</topic><topic>Deoxyguanosine</topic><topic>Diastolic pressure</topic><topic>Drug dosages</topic><topic>Drug therapy</topic><topic>Enzyme inhibitors</topic><topic>Ethics</topic><topic>Fatty acid-binding protein</topic><topic>Fatty acids</topic><topic>Female</topic><topic>Flow velocity</topic><topic>Gout</topic><topic>Health care</topic><topic>Heart failure</topic><topic>Heart Failure - complications</topic><topic>Heart Failure - drug therapy</topic><topic>Heart Failure - metabolism</topic><topic>Heart Failure - physiopathology</topic><topic>Heart valves</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Hypertension</topic><topic>Hyperuricemia</topic><topic>Hyperuricemia - drug therapy</topic><topic>Hyperuricemia - etiology</topic><topic>Hyperuricemia - metabolism</topic><topic>Hyperuricemia - physiopathology</topic><topic>Internal medicine</topic><topic>Male</topic><topic>Medicine and Health Sciences</topic><topic>Middle Aged</topic><topic>Mitral valve</topic><topic>Mortality</topic><topic>Natriuretic Peptide, Brain - metabolism</topic><topic>Nitriles - administration & dosage</topic><topic>Nitriles - therapeutic use</topic><topic>Oxidative stress</topic><topic>Oxidoreductase</topic><topic>Patients</topic><topic>Peptide Fragments - metabolism</topic><topic>Peptides</topic><topic>Physical Sciences</topic><topic>Preventive medicine</topic><topic>Prospective Studies</topic><topic>Pyridines - administration & dosage</topic><topic>Pyridines - therapeutic use</topic><topic>Research and Analysis Methods</topic><topic>Rheumatism</topic><topic>Stroke Volume - drug effects</topic><topic>Testing</topic><topic>Treatment Outcome</topic><topic>Uric acid</topic><topic>Valve leaflets</topic><topic>Velocity</topic><topic>Ventricle</topic><topic>Xanthine oxidase</topic><topic>Xanthine oxidoreductase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sakuma, Masashi</creatorcontrib><creatorcontrib>Toyoda, Shigeru</creatorcontrib><creatorcontrib>Arikawa, Takuo</creatorcontrib><creatorcontrib>Koyabu, Yota</creatorcontrib><creatorcontrib>Kato, Toru</creatorcontrib><creatorcontrib>Adachi, Taichi</creatorcontrib><creatorcontrib>Suwa, Hideaki</creatorcontrib><creatorcontrib>Narita, Jun-Ichi</creatorcontrib><creatorcontrib>Anraku, Koetsu</creatorcontrib><creatorcontrib>Ishimura, Kimihiko</creatorcontrib><creatorcontrib>Yamauchi, Fumitake</creatorcontrib><creatorcontrib>Sato, Yasunori</creatorcontrib><creatorcontrib>Inoue, Teruo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sakuma, Masashi</au><au>Toyoda, Shigeru</au><au>Arikawa, Takuo</au><au>Koyabu, Yota</au><au>Kato, Toru</au><au>Adachi, Taichi</au><au>Suwa, Hideaki</au><au>Narita, Jun-Ichi</au><au>Anraku, Koetsu</au><au>Ishimura, Kimihiko</au><au>Yamauchi, Fumitake</au><au>Sato, Yasunori</au><au>Inoue, Teruo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Topiroxostat versus allopurinol in patients with chronic heart failure complicated by hyperuricemia: A prospective, randomized, open-label, blinded-end-point clinical trial</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2022-01-25</date><risdate>2022</risdate><volume>17</volume><issue>1</issue><spage>e0261445</spage><epage>e0261445</epage><pages>e0261445-e0261445</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The benefits of xanthine oxidase inhibitors to chronic heart failure (CHF) patients is controversial. We investigated the beneficial effects of a novel xanthine oxidoreductase inhibitor, topiroxostat, in patients with CHF and hyperuricemia (HU), in comparison to allopurinol.
The prospective, randomized open-label, blinded-end-point study was performed in 141 patients with CHF and HU at 4 centers. Patients were randomly assigned to either topiroxostat or allopurinol group to achieve target uric acid level ≤6.0 mg/dL. According to the protocol, 140 patients were followed up for 24 weeks. Percent change in ln (N-terminal-proB-type natriuretic peptide) at week 24 (primary endpoint) was comparable between topiroxostat and allopurinol groups (1.6±8.2 versus -0.4±8.0%; P = 0.17). In the limited number of patients with heart failure with reduced ejection fraction (HFrEF) (left ventricle ejection fraction <45%), ratio of peak early diastolic flow velocity at mitral valve leaflet to early diastolic mitral annular motion velocity (E/e') decreased in topiroxostat group, but not in allopurinol group. Urinary 8-hydroxy-2'-deoxyguanosine and L-type fatty acid-binding protein levels increased and osmolality decreased significantly in allopurinol group, while these changes were less or absent in topiroxostat group. In allopurinol group HFrEF patients, additional to the increases in these urinary marker levels, urinary creatinine levels decreased, with no change in clearance, but not in topiroxostat group.
Compared with allopurinol, topiroxostat did not show great benefits in patients with CHF and HU. However, topiroxostat might have potential advantages of reducing left ventricular end-diastolic pressure, not worsening oxidative stress in proximal renal tubule, and renoprotection over allopurinol in HFrEF patients.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>35077456</pmid><doi>10.1371/journal.pone.0261445</doi><tpages>e0261445</tpages><orcidid>https://orcid.org/0000-0002-3892-0799</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2022-01, Vol.17 (1), p.e0261445-e0261445 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2622771663 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Aged Aged, 80 and over Allopurinol Allopurinol - administration & dosage Allopurinol - therapeutic use Biology and Life Sciences Biomarkers Biomarkers - urine Blood pressure Cardiology Care and treatment Clinical trials Comparative analysis Congestive heart failure Creatinine Deoxyguanosine Diastolic pressure Drug dosages Drug therapy Enzyme inhibitors Ethics Fatty acid-binding protein Fatty acids Female Flow velocity Gout Health care Heart failure Heart Failure - complications Heart Failure - drug therapy Heart Failure - metabolism Heart Failure - physiopathology Heart valves Hospitals Humans Hypertension Hyperuricemia Hyperuricemia - drug therapy Hyperuricemia - etiology Hyperuricemia - metabolism Hyperuricemia - physiopathology Internal medicine Male Medicine and Health Sciences Middle Aged Mitral valve Mortality Natriuretic Peptide, Brain - metabolism Nitriles - administration & dosage Nitriles - therapeutic use Oxidative stress Oxidoreductase Patients Peptide Fragments - metabolism Peptides Physical Sciences Preventive medicine Prospective Studies Pyridines - administration & dosage Pyridines - therapeutic use Research and Analysis Methods Rheumatism Stroke Volume - drug effects Testing Treatment Outcome Uric acid Valve leaflets Velocity Ventricle Xanthine oxidase Xanthine oxidoreductase |
| title | Topiroxostat versus allopurinol in patients with chronic heart failure complicated by hyperuricemia: A prospective, randomized, open-label, blinded-end-point clinical trial |
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