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Body fluid regulation via chronic inhibition of sodium–glucose cotransporter-2 in patients with heart failure: a post hoc analysis of the CANDLE trial
Background In patients with chronic heart failure (CHF) and type 2 diabetes (T2D), sodium–glucose cotransporter-2 (SGLT2) inhibition improves cardiorenal outcomes, but details of the effects on distinct subsets of body fluid volume remain incomplete. Methods This was a post hoc analysis of patients...
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| Published in: | Clinical research in cardiology 2023, Vol.112 (1), p.87-97 |
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| container_title | Clinical research in cardiology |
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| creator | Fujiki, Shinya Tanaka, Atsushi Imai, Takumi Shimabukuro, Michio Uehara, Hiroki Nakamura, Ikuko Matsunaga, Kazuo Suzuki, Makoto Kashimura, Takeshi Minamino, Tohru Inomata, Takayuki Node, Koichi |
| description | Background
In patients with chronic heart failure (CHF) and type 2 diabetes (T2D), sodium–glucose cotransporter-2 (SGLT2) inhibition improves cardiorenal outcomes, but details of the effects on distinct subsets of body fluid volume remain incomplete.
Methods
This was a post hoc analysis of patients with CHF and T2D in the CANDLE trial (UMIN000017669), an investigator-initiated, multi-center, randomized open-label trial that compared the effect of canagliflozin (100 mg,
n
= 113) with glimepiride (starting dose: 0.5 mg,
n
= 120) on changes in N-terminal pro-brain natriuretic peptide. The estimated plasma volume (ePV, calculated with the Straus formula) and estimated extracellular volume (eEV, determined by the body surface area) were compared between treatment groups at weeks 4, 12, and 24.
Results
Among 233 patients analyzed, 166 (71.2%) had an ejection fraction (EF) > 50%. Reductions in ePV and eEV were observed only in the canagliflozin group until week 12 (change from baseline at week 12, ePV; − 7.63%; 95% confidence interval [CI], − 10.71 to − 4.55%,
p
|
| doi_str_mv | 10.1007/s00392-022-02049-4 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2679699250</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2766576216</sourcerecordid><originalsourceid>FETCH-LOGICAL-c375t-8917536102cbc79c2646fb0263f268c257adc6cc51273a2e5f991884c357b84a3</originalsourceid><addsrcrecordid>eNp9kbtuFDEUhkcIRELgBSiQJRqaIb57TBeWQCKtoIHa8ng8O46848EX0Ha8Q5o8H0-CN5sEiYLCsmV_57fO-ZrmJYJvEYTiNEFIJG4h3i9IZUsfNceo46iFXOLHD-eOHjXPUrqCkCFI6NPmiDCBJSXwuLl5H4YdGH1xA4h2U7zOLszgh9PATDHMzgA3T653t9dhBCkMrmx__7re-GJCssCEHPWclhCzjS2uOFhqiJ1zAj9dnsBkdcxg1M6XaN8BDZaQMpiCAXrWfpdc2ufmyYLV2ecP63OQo9P-efNk1D7ZF3f7SfPt4_nX1UW7_vLpcnW2bg0RLLedRIIRjiA2vRHSYE752EPMyYh5ZzATejDcGIawIBpbNkqJuo6aOoK-o5qcNG8OuUsM34tNWW1dMtZ7PdtQksJcSC4lZrCir_9Br0KJtYdKCc6Z4BjxSuEDZWJIKdpRLdFtddwpBNXemzp4U9WbuvWmaC16dRdd-q0dHkruRVWAHIBUn-aNjX___k_sH1DqpG4</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2766576216</pqid></control><display><type>article</type><title>Body fluid regulation via chronic inhibition of sodium–glucose cotransporter-2 in patients with heart failure: a post hoc analysis of the CANDLE trial</title><source>Springer Link</source><creator>Fujiki, Shinya ; Tanaka, Atsushi ; Imai, Takumi ; Shimabukuro, Michio ; Uehara, Hiroki ; Nakamura, Ikuko ; Matsunaga, Kazuo ; Suzuki, Makoto ; Kashimura, Takeshi ; Minamino, Tohru ; Inomata, Takayuki ; Node, Koichi</creator><creatorcontrib>Fujiki, Shinya ; Tanaka, Atsushi ; Imai, Takumi ; Shimabukuro, Michio ; Uehara, Hiroki ; Nakamura, Ikuko ; Matsunaga, Kazuo ; Suzuki, Makoto ; Kashimura, Takeshi ; Minamino, Tohru ; Inomata, Takayuki ; Node, Koichi ; CANDLE Trial Investigators ; the CANDLE Trial Investigators</creatorcontrib><description>Background
In patients with chronic heart failure (CHF) and type 2 diabetes (T2D), sodium–glucose cotransporter-2 (SGLT2) inhibition improves cardiorenal outcomes, but details of the effects on distinct subsets of body fluid volume remain incomplete.
Methods
This was a post hoc analysis of patients with CHF and T2D in the CANDLE trial (UMIN000017669), an investigator-initiated, multi-center, randomized open-label trial that compared the effect of canagliflozin (100 mg,
n
= 113) with glimepiride (starting dose: 0.5 mg,
n
= 120) on changes in N-terminal pro-brain natriuretic peptide. The estimated plasma volume (ePV, calculated with the Straus formula) and estimated extracellular volume (eEV, determined by the body surface area) were compared between treatment groups at weeks 4, 12, and 24.
Results
Among 233 patients analyzed, 166 (71.2%) had an ejection fraction (EF) > 50%. Reductions in ePV and eEV were observed only in the canagliflozin group until week 12 (change from baseline at week 12, ePV; − 7.63%; 95% confidence interval [CI], − 10.71 to − 4.55%,
p
< 0.001, eEV; − 123.15 mL; 95% CI, − 190.38 to − 55.92 mL,
p
< 0.001). While ePV stopped falling after week 12, eEV continued to fall until week 24 ([change from baseline at week 24] − [change from baseline at week 12], ePV; 1.01%; 95%CI, − 2.30–4.32%,
p
= 0.549, eEV; − 125.15 mL; 95% CI, − 184.35 to − 65.95 mL,
p
< 0.001).
Conclusions
Maintenance of a modest reduction in ePV and continuous removal of eEV via chronic SGLT2 inhibition suggests that favorable body fluid regulation contributes to the cardiorenal benefits of SGLT2 inhibitors in patients with CHF, irrespective of EF.
Trial Registration
UMIN000017669.
Graphical abstract</description><identifier>ISSN: 1861-0684</identifier><identifier>EISSN: 1861-0692</identifier><identifier>DOI: 10.1007/s00392-022-02049-4</identifier><identifier>PMID: 35729430</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Body Fluids ; Brain natriuretic peptide ; Canagliflozin - therapeutic use ; Cardiology ; Chronic Disease ; Congestive heart failure ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 2 - complications ; Diabetes Mellitus, Type 2 - drug therapy ; Failure analysis ; Glucose ; Glucosides - pharmacology ; Heart failure ; Heart Failure - drug therapy ; Humans ; Medicine ; Medicine & Public Health ; Na+/glucose cotransporter ; Original Paper ; Sodium ; Sodium-Glucose Transporter 2 ; Sodium-Glucose Transporter 2 Inhibitors - therapeutic use</subject><ispartof>Clinical research in cardiology, 2023, Vol.112 (1), p.87-97</ispartof><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany 2022</rights><rights>2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.</rights><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany 2022.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-8917536102cbc79c2646fb0263f268c257adc6cc51273a2e5f991884c357b84a3</citedby><cites>FETCH-LOGICAL-c375t-8917536102cbc79c2646fb0263f268c257adc6cc51273a2e5f991884c357b84a3</cites><orcidid>0000-0002-9412-1254</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35729430$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fujiki, Shinya</creatorcontrib><creatorcontrib>Tanaka, Atsushi</creatorcontrib><creatorcontrib>Imai, Takumi</creatorcontrib><creatorcontrib>Shimabukuro, Michio</creatorcontrib><creatorcontrib>Uehara, Hiroki</creatorcontrib><creatorcontrib>Nakamura, Ikuko</creatorcontrib><creatorcontrib>Matsunaga, Kazuo</creatorcontrib><creatorcontrib>Suzuki, Makoto</creatorcontrib><creatorcontrib>Kashimura, Takeshi</creatorcontrib><creatorcontrib>Minamino, Tohru</creatorcontrib><creatorcontrib>Inomata, Takayuki</creatorcontrib><creatorcontrib>Node, Koichi</creatorcontrib><creatorcontrib>CANDLE Trial Investigators</creatorcontrib><creatorcontrib>the CANDLE Trial Investigators</creatorcontrib><title>Body fluid regulation via chronic inhibition of sodium–glucose cotransporter-2 in patients with heart failure: a post hoc analysis of the CANDLE trial</title><title>Clinical research in cardiology</title><addtitle>Clin Res Cardiol</addtitle><addtitle>Clin Res Cardiol</addtitle><description>Background
In patients with chronic heart failure (CHF) and type 2 diabetes (T2D), sodium–glucose cotransporter-2 (SGLT2) inhibition improves cardiorenal outcomes, but details of the effects on distinct subsets of body fluid volume remain incomplete.
Methods
This was a post hoc analysis of patients with CHF and T2D in the CANDLE trial (UMIN000017669), an investigator-initiated, multi-center, randomized open-label trial that compared the effect of canagliflozin (100 mg,
n
= 113) with glimepiride (starting dose: 0.5 mg,
n
= 120) on changes in N-terminal pro-brain natriuretic peptide. The estimated plasma volume (ePV, calculated with the Straus formula) and estimated extracellular volume (eEV, determined by the body surface area) were compared between treatment groups at weeks 4, 12, and 24.
Results
Among 233 patients analyzed, 166 (71.2%) had an ejection fraction (EF) > 50%. Reductions in ePV and eEV were observed only in the canagliflozin group until week 12 (change from baseline at week 12, ePV; − 7.63%; 95% confidence interval [CI], − 10.71 to − 4.55%,
p
< 0.001, eEV; − 123.15 mL; 95% CI, − 190.38 to − 55.92 mL,
p
< 0.001). While ePV stopped falling after week 12, eEV continued to fall until week 24 ([change from baseline at week 24] − [change from baseline at week 12], ePV; 1.01%; 95%CI, − 2.30–4.32%,
p
= 0.549, eEV; − 125.15 mL; 95% CI, − 184.35 to − 65.95 mL,
p
< 0.001).
Conclusions
Maintenance of a modest reduction in ePV and continuous removal of eEV via chronic SGLT2 inhibition suggests that favorable body fluid regulation contributes to the cardiorenal benefits of SGLT2 inhibitors in patients with CHF, irrespective of EF.
Trial Registration
UMIN000017669.
Graphical abstract</description><subject>Body Fluids</subject><subject>Brain natriuretic peptide</subject><subject>Canagliflozin - therapeutic use</subject><subject>Cardiology</subject><subject>Chronic Disease</subject><subject>Congestive heart failure</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Diabetes Mellitus, Type 2 - complications</subject><subject>Diabetes Mellitus, Type 2 - drug therapy</subject><subject>Failure analysis</subject><subject>Glucose</subject><subject>Glucosides - pharmacology</subject><subject>Heart failure</subject><subject>Heart Failure - drug therapy</subject><subject>Humans</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Na+/glucose cotransporter</subject><subject>Original Paper</subject><subject>Sodium</subject><subject>Sodium-Glucose Transporter 2</subject><subject>Sodium-Glucose Transporter 2 Inhibitors - therapeutic use</subject><issn>1861-0684</issn><issn>1861-0692</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNp9kbtuFDEUhkcIRELgBSiQJRqaIb57TBeWQCKtoIHa8ng8O46848EX0Ha8Q5o8H0-CN5sEiYLCsmV_57fO-ZrmJYJvEYTiNEFIJG4h3i9IZUsfNceo46iFXOLHD-eOHjXPUrqCkCFI6NPmiDCBJSXwuLl5H4YdGH1xA4h2U7zOLszgh9PATDHMzgA3T653t9dhBCkMrmx__7re-GJCssCEHPWclhCzjS2uOFhqiJ1zAj9dnsBkdcxg1M6XaN8BDZaQMpiCAXrWfpdc2ufmyYLV2ecP63OQo9P-efNk1D7ZF3f7SfPt4_nX1UW7_vLpcnW2bg0RLLedRIIRjiA2vRHSYE752EPMyYh5ZzATejDcGIawIBpbNkqJuo6aOoK-o5qcNG8OuUsM34tNWW1dMtZ7PdtQksJcSC4lZrCir_9Br0KJtYdKCc6Z4BjxSuEDZWJIKdpRLdFtddwpBNXemzp4U9WbuvWmaC16dRdd-q0dHkruRVWAHIBUn-aNjX___k_sH1DqpG4</recordid><startdate>2023</startdate><enddate>2023</enddate><creator>Fujiki, Shinya</creator><creator>Tanaka, Atsushi</creator><creator>Imai, Takumi</creator><creator>Shimabukuro, Michio</creator><creator>Uehara, Hiroki</creator><creator>Nakamura, Ikuko</creator><creator>Matsunaga, Kazuo</creator><creator>Suzuki, Makoto</creator><creator>Kashimura, Takeshi</creator><creator>Minamino, Tohru</creator><creator>Inomata, Takayuki</creator><creator>Node, Koichi</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M7Z</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-9412-1254</orcidid></search><sort><creationdate>2023</creationdate><title>Body fluid regulation via chronic inhibition of sodium–glucose cotransporter-2 in patients with heart failure: a post hoc analysis of the CANDLE trial</title><author>Fujiki, Shinya ; Tanaka, Atsushi ; Imai, Takumi ; Shimabukuro, Michio ; Uehara, Hiroki ; Nakamura, Ikuko ; Matsunaga, Kazuo ; Suzuki, Makoto ; Kashimura, Takeshi ; Minamino, Tohru ; Inomata, Takayuki ; Node, Koichi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-8917536102cbc79c2646fb0263f268c257adc6cc51273a2e5f991884c357b84a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Body Fluids</topic><topic>Brain natriuretic peptide</topic><topic>Canagliflozin - therapeutic use</topic><topic>Cardiology</topic><topic>Chronic Disease</topic><topic>Congestive heart failure</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>Diabetes Mellitus, Type 2 - complications</topic><topic>Diabetes Mellitus, Type 2 - drug therapy</topic><topic>Failure analysis</topic><topic>Glucose</topic><topic>Glucosides - pharmacology</topic><topic>Heart failure</topic><topic>Heart Failure - drug therapy</topic><topic>Humans</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Na+/glucose cotransporter</topic><topic>Original Paper</topic><topic>Sodium</topic><topic>Sodium-Glucose Transporter 2</topic><topic>Sodium-Glucose Transporter 2 Inhibitors - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fujiki, Shinya</creatorcontrib><creatorcontrib>Tanaka, Atsushi</creatorcontrib><creatorcontrib>Imai, Takumi</creatorcontrib><creatorcontrib>Shimabukuro, Michio</creatorcontrib><creatorcontrib>Uehara, Hiroki</creatorcontrib><creatorcontrib>Nakamura, Ikuko</creatorcontrib><creatorcontrib>Matsunaga, Kazuo</creatorcontrib><creatorcontrib>Suzuki, Makoto</creatorcontrib><creatorcontrib>Kashimura, Takeshi</creatorcontrib><creatorcontrib>Minamino, Tohru</creatorcontrib><creatorcontrib>Inomata, Takayuki</creatorcontrib><creatorcontrib>Node, Koichi</creatorcontrib><creatorcontrib>CANDLE Trial Investigators</creatorcontrib><creatorcontrib>the CANDLE Trial Investigators</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Biochemistry Abstracts 1</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical research in cardiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fujiki, Shinya</au><au>Tanaka, Atsushi</au><au>Imai, Takumi</au><au>Shimabukuro, Michio</au><au>Uehara, Hiroki</au><au>Nakamura, Ikuko</au><au>Matsunaga, Kazuo</au><au>Suzuki, Makoto</au><au>Kashimura, Takeshi</au><au>Minamino, Tohru</au><au>Inomata, Takayuki</au><au>Node, Koichi</au><aucorp>CANDLE Trial Investigators</aucorp><aucorp>the CANDLE Trial Investigators</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Body fluid regulation via chronic inhibition of sodium–glucose cotransporter-2 in patients with heart failure: a post hoc analysis of the CANDLE trial</atitle><jtitle>Clinical research in cardiology</jtitle><stitle>Clin Res Cardiol</stitle><addtitle>Clin Res Cardiol</addtitle><date>2023</date><risdate>2023</risdate><volume>112</volume><issue>1</issue><spage>87</spage><epage>97</epage><pages>87-97</pages><issn>1861-0684</issn><eissn>1861-0692</eissn><abstract>Background
In patients with chronic heart failure (CHF) and type 2 diabetes (T2D), sodium–glucose cotransporter-2 (SGLT2) inhibition improves cardiorenal outcomes, but details of the effects on distinct subsets of body fluid volume remain incomplete.
Methods
This was a post hoc analysis of patients with CHF and T2D in the CANDLE trial (UMIN000017669), an investigator-initiated, multi-center, randomized open-label trial that compared the effect of canagliflozin (100 mg,
n
= 113) with glimepiride (starting dose: 0.5 mg,
n
= 120) on changes in N-terminal pro-brain natriuretic peptide. The estimated plasma volume (ePV, calculated with the Straus formula) and estimated extracellular volume (eEV, determined by the body surface area) were compared between treatment groups at weeks 4, 12, and 24.
Results
Among 233 patients analyzed, 166 (71.2%) had an ejection fraction (EF) > 50%. Reductions in ePV and eEV were observed only in the canagliflozin group until week 12 (change from baseline at week 12, ePV; − 7.63%; 95% confidence interval [CI], − 10.71 to − 4.55%,
p
< 0.001, eEV; − 123.15 mL; 95% CI, − 190.38 to − 55.92 mL,
p
< 0.001). While ePV stopped falling after week 12, eEV continued to fall until week 24 ([change from baseline at week 24] − [change from baseline at week 12], ePV; 1.01%; 95%CI, − 2.30–4.32%,
p
= 0.549, eEV; − 125.15 mL; 95% CI, − 184.35 to − 65.95 mL,
p
< 0.001).
Conclusions
Maintenance of a modest reduction in ePV and continuous removal of eEV via chronic SGLT2 inhibition suggests that favorable body fluid regulation contributes to the cardiorenal benefits of SGLT2 inhibitors in patients with CHF, irrespective of EF.
Trial Registration
UMIN000017669.
Graphical abstract</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>35729430</pmid><doi>10.1007/s00392-022-02049-4</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-9412-1254</orcidid></addata></record> |
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| identifier | ISSN: 1861-0684 |
| ispartof | Clinical research in cardiology, 2023, Vol.112 (1), p.87-97 |
| issn | 1861-0684 1861-0692 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2679699250 |
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| subjects | Body Fluids Brain natriuretic peptide Canagliflozin - therapeutic use Cardiology Chronic Disease Congestive heart failure Diabetes mellitus (non-insulin dependent) Diabetes Mellitus, Type 2 - complications Diabetes Mellitus, Type 2 - drug therapy Failure analysis Glucose Glucosides - pharmacology Heart failure Heart Failure - drug therapy Humans Medicine Medicine & Public Health Na+/glucose cotransporter Original Paper Sodium Sodium-Glucose Transporter 2 Sodium-Glucose Transporter 2 Inhibitors - therapeutic use |
| title | Body fluid regulation via chronic inhibition of sodium–glucose cotransporter-2 in patients with heart failure: a post hoc analysis of the CANDLE trial |
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