Treatment of dogs with compensated myxomatous mitral valve disease with spironolactone—a pilot study

Hezzell, Melanie J; Boswood, Adrian; López-Alvarez, Jordi; Lotter, Nicola; Elliott, Jonathan

doi:10.1016/j.jvc.2017.06.001

Cited by 6 publications

(8 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This is presumably due to displacement of aldosterone from mineralocorticoid receptors by spironolactone and subsequently increased circulating aldosterone concentrations. This is consistent with previous studies showing increased circulating serum [24] and urine [7,13,26] aldosterone concentrations with spironolactone treatment in dogs. In another study using low dose spironolactone at a median dose of 0.52 mg/kg/day, there was no increase in circulating plasma aldosterone.…”

Section: Discussionsupporting

confidence: 93%

“…[11] Due to the documented survival bene t of MRA treatment in patients with CHF and the recognized importance of ABT in cardiovascular disease pathology, the most recent consensus guidelines from the American College of Veterinary Internal Medicine (ACVIM) recommend treatment with spironolactone at a dosage of 2.0 mg/kg by mouth every 12-24 hours for aldosterone antagonism in stage C MMVD. [12] However, despite the demonstrated clinical bene t of spironolactone in canine CHF [2,3,13,14], it remains unknown exactly how spironolactone affects the classical and alternative arms of the RAAS pathway.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Comprehensive characterization of the effect of mineralocorticoid receptor antagonism with spironolactone on the renin-angiotensin-aldosterone system in healthy dogs.

Masters

Ward

Guillot³

et al. 2023

Preprint

View full text Add to dashboard Cite

Objective – To characterize the dose-exposure-response effect of spironolactone on biomarkers of the classical and alternative arms of the renin-angiotensin-aldosterone system (RAAS) in healthy dogs. Animals – Ten healthy purpose-bred Beagle dogs. Procedures – Study dogs were randomly allocated to 2 spironolactone dosing groups (2 mg/kg PO q24hr, 4 mg/kg PO q24hr). The dogs received 7-day courses of spironolactone followed by a 14-day washout period in a crossover (AB/BA) design. Angiotensin peptides and aldosterone were measured in serum using equilibrium analysis, and plasma canrenone and 7-α-thiomethyl spironolactone (TMS) were quantified via liquid chromatography-mass spectrometry/mass spectroscopy (LC-MS/MS). Study results were compared before and after dosing and between groups. Results – Following spironolactone treatment, dogs had a significant increase in serum aldosterone concentration (P = 0.07), with no statistical differences between dosing groups. Significant increases in angiotensin II (P = 0.09), angiotensin I (P = 0.08), angiotensin 1–5 (P = 0.08), and a surrogate marker for plasma renin activity (P = 0.06) were detected compared to baseline following spironolactone treatment during the second treatment period only. Overall, changes from baseline did not significantly differ between spironolactone dosages. RAAS analytes were weakly correlated (R < 0.4) with spironolactone dosage and plasma canrenone or plasma TMS. There were no adverse clinical or biochemical effects seen at any spironolactone dosage during treatment. Conclusions – Treatment with spironolactone increased serum aldosterone concentration in healthy dogs and impacted other biomarkers of the classical and alternative arms of the RAAS. There was no difference in effect on the RAAS between 2 and 4 mg/kg/day dosing. Dosage of 4 mg/kg/day was safe and well-tolerated in healthy dogs.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Comprehensive characterization of the effect of mineralocorticoid receptor antagonism with spironolactone on the renin-angiotensin-aldosterone system in healthy dogs.

Masters

Ward

Guillot³

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…(Class III, LOE: weak) Spironolactone also is not recommended for routine use to delay the onset of heart failure in dogs. Clinical trials addressing the efficacy of spironolactone for the treatment of dogs in Stage B2 have not been published as of this writing (2019), although a pilot study suggests this approach should be used (Class IIb, LOE: expert opinion). No other pharmacologic treatments for Stage B were recommended by a majority of panelists. A few panelists considered the use of the following medications for patients in advanced Stage B2 under specific circumstances: beta blockers, amlodipine.…”

Section: Guidelines For Diagnosis and Treatment Of Mmvdmentioning

confidence: 99%

ACVIM consensus guidelines for the diagnosis and treatment of myxomatous mitral valve disease in dogs

Keene

Atkins

Bonagura

et al. 2019

Veterinary Internal Medicne

491

880

View full text Add to dashboard Cite

This report, issued by the ACVIM Specialty of Cardiology consensus panel, revises guidelines for the diagnosis and treatment of myxomatous mitral valve disease (MMVD, also known as endocardiosis and degenerative or chronic valvular heart disease) in dogs, originally published in 2009. Updates were made to diagnostic, as well as medical, surgical, and dietary treatment recommendations. The strength of these recommendations was based on both the quantity and quality of available evidence supporting diagnostic and therapeutic decisions. Management of MMVD before the onset of clinical signs of heart failure has changed substantially compared with the 2009 guidelines, and new strategies to diagnose and treat advanced heart failure and pulmonary hypertension are reviewed.

show abstract

“…Bei je 20 Hunden mit MKE im Stadium B2 führte die Gabe von Spironolacton im Vergleich zum Plazebo zu einer geringeren Zunahme von enddiastolischem Diameter, Vorhofgröße und NT-proBNP-Konzentration (38). In einer weiteren kleinen Studie an 54 Hunden mit MKE ergab sich eine Korrelation zwischen erhöhten Aldosteronwerten und schnellerer Progression der Erkrankung sowie verringerter Überlebenswahrscheinlichkeit (37…”

Section: Hemmer Des Angiotensin-konvertierenden Enzymsunclassified

Therapie der Mitralklappenendokardiose beim Hund – ein Update

Hungerbühler¹,

Henrich²

2017

Tierarztl Prax Ausg K

View full text Add to dashboard Cite

ZusammenfassungAnhand von Anamnese, Signalement, Auskultations- und Röntgenbefund lässt sich bei Hunden die Verdachtsdiagnose der Mitralklappenendokardiose stellen. Die definitive Diagnosestellung und die genaue Bestimmung des Schweregrades erfordern jedoch eine radiologische Größenbeurteilung des Herzens und eine echokardiographische Evaluierung. Mithilfe der Anzeichen der Volumenbelastung kann so zwischen den Stadien B1 und B2 unterschieden werden. Im Stadium A und B1 bedarf es keiner Therapie, eine halbjährliche bis jährliche kardiologische Kontrolle sollte vorgenommen werden, um die Progression der Erkrankung zu beurteilen. Hinsichtlich der Behandlung im Stadium B2 bestand 2009 noch kein Konsens, doch ist heutzutage aufgrund der EPIC-Studie bei diesen Patienten die lebensverlängernde Wirkung von Pimobendan bewiesen. Nach den Resultaten überwiegend experimenteller Studien, in denen sich bei Gabe eines Hemmers des Angiotensin-konvertierenden Enzyms (ACE-H) ein Aldosteron-Escape-Mechanismus ergab, könnte die Hemmung des Renin-Angiotensin-Aldosteron-Systems durch Kombination von ACE-H und Spironolacton ebenfalls schon im Stadium B2 ein vielversprechender Therapieansatz sein. Für eine endgültige Entscheidung bleibt jedoch die DELAY-Stu die abzuwarten. Bei Hunden im akut lebensbedrohlichen dekompensierten Stadium C3 muss zunächst eine Stabilisierung mittels Steigerung der Diurese, positiv inotropen Medikamenten (Pimobendan) und Sauerstoffsubstitution erfolgen. Eine kontinuierliche Kontrolle der wichtigsten Vitalparameter ist durchzuführen. Anhand dieser Befunde wird die Therapie, insbesondere die Dosierung des Diuretikums, angepasst. Daher ist diese Behandlung nur unter intensivme dizinischer Betreuung möglich. Zur Therapie im chronischen Stadium C 1/2 wird das Vierfach-Therapieprotokoll bestehend aus Furosemid, Pimobendan, ACE-H und Spironolacton angeraten. Das Schleifendiuretikum Torasemid stellt dabei eine Alternative zu Furosemid dar. Hunde im Stadium D (trotz medikamentöser Therapie weiterhin refraktäres Herzversagen) sind schwierig zu stabilisieren und haben eine schlechte Prognose. Zur Stabilisierung finden üblicherweise Methoden Anwendung, die bislang nicht evidenzbasiert untersucht wurden.

show abstract

Treatment of dogs with compensated myxomatous mitral valve disease with spironolactone—a pilot study

Cited by 6 publications

References 29 publications

Comprehensive characterization of the effect of mineralocorticoid receptor antagonism with spironolactone on the renin-angiotensin-aldosterone system in healthy dogs.

Comprehensive characterization of the effect of mineralocorticoid receptor antagonism with spironolactone on the renin-angiotensin-aldosterone system in healthy dogs.

ACVIM consensus guidelines for the diagnosis and treatment of myxomatous mitral valve disease in dogs

Therapie der Mitralklappenendokardiose beim Hund – ein Update

Contact Info

Product

Resources

About