Treatment of dogs with compensated myxomatous mitral valve disease with spironolactone—a pilot study
Spironolactone improves outcome in dogs with advanced myxomatous mitral valve disease (MMVD). Its efficacy in preclinical MMVD is unknown. The hypothesis was the administration of spironolactone to dogs with compensated MMVD demonstrating risk factors for poorer prognosis will decrease the rate of d...
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Veröffentlicht in: | Journal of veterinary cardiology 2017-08, Vol.19 (4), p.325-338 |
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creator | Hezzell, M.J. Boswood, A. López-Alvarez, J. Lötter, N. Elliott, J. |
description | Spironolactone improves outcome in dogs with advanced myxomatous mitral valve disease (MMVD). Its efficacy in preclinical MMVD is unknown. The hypothesis was the administration of spironolactone to dogs with compensated MMVD demonstrating risk factors for poorer prognosis will decrease the rate of disease progression. The aim was to provide pilot data to evaluate preliminary effects and sample size calculation for a definitive clinical trial.
Twenty-five client-owned dogs with MMVD with at least one of the following; left atrial to aortic ratio (LA:Ao) ≥ 1.5, normalized left ventricular internal diameter in diastole ≥ 1.6), N-terminal pro-B-type natriuretic peptide (NT-proBNP) > 550 pmol/L, cardiac troponin I > 0.025 ng/mL.
Prospective, single-center, equally randomized, placebo-controlled, double-blinded, parallel grouped pilot study. No dogs were receiving medications for cardiac disease before the enrollment.
Twelve dogs received placebo; 13 received spironolactone. One dog in the spironolactone group died suddenly, 1 developed congestive heart failure, and 2 received suboptimal spironolactone doses. At enrollment, NT-proBNP was significantly higher in the spironolactone group (p=0.005). Left atrial to aortic ratio (p=0.002) and left ventricular internal diameter in diastole (p=0.005) increased over time in the placebo group, but not the spironolactone group; the change did not differ significantly between groups. The change in biomarker concentrations did not differ significantly between groups; there was a tendency toward an increase in NT-proBNP over time in the placebo group. Enrollment of 76 dogs would be necessary to demonstrate a difference in the change in LA:Ao over 6 months between the groups.
Preliminary results support undertaking a larger clinical trial of treatment of dogs with preclinical MMVD with spironolactone. |
doi_str_mv | 10.1016/j.jvc.2017.06.001 |
format | Article |
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Twenty-five client-owned dogs with MMVD with at least one of the following; left atrial to aortic ratio (LA:Ao) ≥ 1.5, normalized left ventricular internal diameter in diastole ≥ 1.6), N-terminal pro-B-type natriuretic peptide (NT-proBNP) > 550 pmol/L, cardiac troponin I > 0.025 ng/mL.
Prospective, single-center, equally randomized, placebo-controlled, double-blinded, parallel grouped pilot study. No dogs were receiving medications for cardiac disease before the enrollment.
Twelve dogs received placebo; 13 received spironolactone. One dog in the spironolactone group died suddenly, 1 developed congestive heart failure, and 2 received suboptimal spironolactone doses. At enrollment, NT-proBNP was significantly higher in the spironolactone group (p=0.005). Left atrial to aortic ratio (p=0.002) and left ventricular internal diameter in diastole (p=0.005) increased over time in the placebo group, but not the spironolactone group; the change did not differ significantly between groups. The change in biomarker concentrations did not differ significantly between groups; there was a tendency toward an increase in NT-proBNP over time in the placebo group. Enrollment of 76 dogs would be necessary to demonstrate a difference in the change in LA:Ao over 6 months between the groups.
Preliminary results support undertaking a larger clinical trial of treatment of dogs with preclinical MMVD with spironolactone.</description><identifier>ISSN: 1760-2734</identifier><identifier>EISSN: 1875-0834</identifier><identifier>DOI: 10.1016/j.jvc.2017.06.001</identifier><identifier>PMID: 28734620</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; Canine ; Dog Diseases - drug therapy ; Dogs ; Female ; Heart Valve Diseases - drug therapy ; Heart Valve Diseases - veterinary ; Male ; Mitral Valve - drug effects ; Mitral Valve - physiopathology ; Pilot Projects ; Preclinical disease ; Prospective Studies ; Spironolactone - therapeutic use ; Therapy</subject><ispartof>Journal of veterinary cardiology, 2017-08, Vol.19 (4), p.325-338</ispartof><rights>2017 Elsevier B.V.</rights><rights>Copyright © 2017 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c396t-bef6ae1320db50e9ae5152b02f308d32da7d2f994e0747b8a9fba40fe1a209d63</citedby><cites>FETCH-LOGICAL-c396t-bef6ae1320db50e9ae5152b02f308d32da7d2f994e0747b8a9fba40fe1a209d63</cites><orcidid>0000-0003-1890-6161</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jvc.2017.06.001$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28734620$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hezzell, M.J.</creatorcontrib><creatorcontrib>Boswood, A.</creatorcontrib><creatorcontrib>López-Alvarez, J.</creatorcontrib><creatorcontrib>Lötter, N.</creatorcontrib><creatorcontrib>Elliott, J.</creatorcontrib><title>Treatment of dogs with compensated myxomatous mitral valve disease with spironolactone—a pilot study</title><title>Journal of veterinary cardiology</title><addtitle>J Vet Cardiol</addtitle><description>Spironolactone improves outcome in dogs with advanced myxomatous mitral valve disease (MMVD). Its efficacy in preclinical MMVD is unknown. The hypothesis was the administration of spironolactone to dogs with compensated MMVD demonstrating risk factors for poorer prognosis will decrease the rate of disease progression. The aim was to provide pilot data to evaluate preliminary effects and sample size calculation for a definitive clinical trial.
Twenty-five client-owned dogs with MMVD with at least one of the following; left atrial to aortic ratio (LA:Ao) ≥ 1.5, normalized left ventricular internal diameter in diastole ≥ 1.6), N-terminal pro-B-type natriuretic peptide (NT-proBNP) > 550 pmol/L, cardiac troponin I > 0.025 ng/mL.
Prospective, single-center, equally randomized, placebo-controlled, double-blinded, parallel grouped pilot study. No dogs were receiving medications for cardiac disease before the enrollment.
Twelve dogs received placebo; 13 received spironolactone. One dog in the spironolactone group died suddenly, 1 developed congestive heart failure, and 2 received suboptimal spironolactone doses. At enrollment, NT-proBNP was significantly higher in the spironolactone group (p=0.005). Left atrial to aortic ratio (p=0.002) and left ventricular internal diameter in diastole (p=0.005) increased over time in the placebo group, but not the spironolactone group; the change did not differ significantly between groups. The change in biomarker concentrations did not differ significantly between groups; there was a tendency toward an increase in NT-proBNP over time in the placebo group. Enrollment of 76 dogs would be necessary to demonstrate a difference in the change in LA:Ao over 6 months between the groups.
Preliminary results support undertaking a larger clinical trial of treatment of dogs with preclinical MMVD with spironolactone.</description><subject>Animals</subject><subject>Canine</subject><subject>Dog Diseases - drug therapy</subject><subject>Dogs</subject><subject>Female</subject><subject>Heart Valve Diseases - drug therapy</subject><subject>Heart Valve Diseases - veterinary</subject><subject>Male</subject><subject>Mitral Valve - drug effects</subject><subject>Mitral Valve - physiopathology</subject><subject>Pilot Projects</subject><subject>Preclinical disease</subject><subject>Prospective Studies</subject><subject>Spironolactone - therapeutic use</subject><subject>Therapy</subject><issn>1760-2734</issn><issn>1875-0834</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1uFDEQhS1ERELgAGyQl2y6Kdv9K1Yo4k-KlE1YW9V2GTzqbje2Z2B2OQQn5CQ4msAytalS6b2nqo-xVwJqAaJ7u6t3B1NLEH0NXQ0gnrALMfRtBYNqnpa576CSvWrO2fOUdgBqkNA_Y-dyKMtOwgVzt5EwL7RmHhy34VviP33-zk1YNloTZrJ8Of4KC-awT3zxOeLMDzgfiFufCBOdDGnzMaxhRpPDSn_ufiPf_BwyT3lvjy_YmcM50cuHfsm-fvxwe_W5ur759OXq_XVl1NjlaiLXIQklwU4t0IjUilZOIJ2CwSppsbfSjWND0Df9NODoJmzAkUAJo-3UJXtzyt1i-LGnlPXik6F5xpXK_VqMUolSrSpScZKaGFKK5PQW_YLxqAXoe7x6pwtefY9XQ6cL3uJ5_RC_nxay_x3_eBbBu5OAypMHT1En42k1ZH0kk7UN_pH4v5zGjlE</recordid><startdate>201708</startdate><enddate>201708</enddate><creator>Hezzell, M.J.</creator><creator>Boswood, A.</creator><creator>López-Alvarez, J.</creator><creator>Lötter, N.</creator><creator>Elliott, J.</creator><general>Elsevier 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>7X8</scope><orcidid>https://orcid.org/0000-0003-1890-6161</orcidid></search><sort><creationdate>201708</creationdate><title>Treatment of dogs with compensated myxomatous mitral valve disease with spironolactone—a pilot study</title><author>Hezzell, M.J. ; Boswood, A. ; López-Alvarez, J. ; Lötter, N. ; Elliott, J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c396t-bef6ae1320db50e9ae5152b02f308d32da7d2f994e0747b8a9fba40fe1a209d63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Canine</topic><topic>Dog Diseases - drug therapy</topic><topic>Dogs</topic><topic>Female</topic><topic>Heart Valve Diseases - drug therapy</topic><topic>Heart Valve Diseases - veterinary</topic><topic>Male</topic><topic>Mitral Valve - drug effects</topic><topic>Mitral Valve - physiopathology</topic><topic>Pilot Projects</topic><topic>Preclinical disease</topic><topic>Prospective Studies</topic><topic>Spironolactone - therapeutic use</topic><topic>Therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hezzell, M.J.</creatorcontrib><creatorcontrib>Boswood, A.</creatorcontrib><creatorcontrib>López-Alvarez, J.</creatorcontrib><creatorcontrib>Lötter, N.</creatorcontrib><creatorcontrib>Elliott, J.</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>Journal of veterinary cardiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hezzell, M.J.</au><au>Boswood, A.</au><au>López-Alvarez, J.</au><au>Lötter, N.</au><au>Elliott, J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Treatment of dogs with compensated myxomatous mitral valve disease with spironolactone—a pilot study</atitle><jtitle>Journal of veterinary cardiology</jtitle><addtitle>J Vet Cardiol</addtitle><date>2017-08</date><risdate>2017</risdate><volume>19</volume><issue>4</issue><spage>325</spage><epage>338</epage><pages>325-338</pages><issn>1760-2734</issn><eissn>1875-0834</eissn><abstract>Spironolactone improves outcome in dogs with advanced myxomatous mitral valve disease (MMVD). Its efficacy in preclinical MMVD is unknown. The hypothesis was the administration of spironolactone to dogs with compensated MMVD demonstrating risk factors for poorer prognosis will decrease the rate of disease progression. The aim was to provide pilot data to evaluate preliminary effects and sample size calculation for a definitive clinical trial.
Twenty-five client-owned dogs with MMVD with at least one of the following; left atrial to aortic ratio (LA:Ao) ≥ 1.5, normalized left ventricular internal diameter in diastole ≥ 1.6), N-terminal pro-B-type natriuretic peptide (NT-proBNP) > 550 pmol/L, cardiac troponin I > 0.025 ng/mL.
Prospective, single-center, equally randomized, placebo-controlled, double-blinded, parallel grouped pilot study. No dogs were receiving medications for cardiac disease before the enrollment.
Twelve dogs received placebo; 13 received spironolactone. One dog in the spironolactone group died suddenly, 1 developed congestive heart failure, and 2 received suboptimal spironolactone doses. At enrollment, NT-proBNP was significantly higher in the spironolactone group (p=0.005). Left atrial to aortic ratio (p=0.002) and left ventricular internal diameter in diastole (p=0.005) increased over time in the placebo group, but not the spironolactone group; the change did not differ significantly between groups. The change in biomarker concentrations did not differ significantly between groups; there was a tendency toward an increase in NT-proBNP over time in the placebo group. Enrollment of 76 dogs would be necessary to demonstrate a difference in the change in LA:Ao over 6 months between the groups.
Preliminary results support undertaking a larger clinical trial of treatment of dogs with preclinical MMVD with spironolactone.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>28734620</pmid><doi>10.1016/j.jvc.2017.06.001</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0003-1890-6161</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Animals Canine Dog Diseases - drug therapy Dogs Female Heart Valve Diseases - drug therapy Heart Valve Diseases - veterinary Male Mitral Valve - drug effects Mitral Valve - physiopathology Pilot Projects Preclinical disease Prospective Studies Spironolactone - therapeutic use Therapy |
title | Treatment of dogs with compensated myxomatous mitral valve disease with spironolactone—a pilot study |
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