Retrospective review of carvedilol administration in 38 dogs with preclinical chronic valvular heart disease
Introduction
Chronic valvular heart disease (CVD) is the most common etiology of both heart disease and congestive heart failure (CHF) in the dog.1 The incidence increases with age in all dogs but small breed dogs, in particular the Cavalier King Charles Spaniel (CKCS), have increased risk.2 CVD is characterized by a long preclinical period. Based on the classification scheme presented in the American College of Veterinary Internal Medicine (ACVIM) Consensus Statement guidelines on the diagnosis and treatment of CVD, dogs with preclinical CVD are categorized as Stage B.3 Prior to the onset of cardiac remodeling, dogs with preclinical CVD are classified as Stage B1. Dogs are classified as Stage B2 once remodeling has progressed to an extent that can be readily detected by radiography and/or echocardiography. Progressive remodeling and the attendant neuroendocrine activation are associated with the development of CHF (Stage C) in some but not all dogs with Stage B CVD.4, 5, 6 A timely effective therapeutic intervention in dogs with Stage B CVD has the potential to delay the onset of CHF and prolong survival.
Currently there is no definitive proof that any medication initiated in either Stage B1 or B2 CVD can delay disease progression or improve survival. This lack of convincing evidence was reflected in the ACVIM Consensus Statement guidelines on the diagnosis and treatment of CVD; although this document did comment on the potential utility of both angiotensin converting enzyme inhibitors (ACEI) and beta-blockers (BB) in a subset of Stage B dogs.3 The reported benefits of chronic beta-blockade in models of chronic mitral regurgitation (MR) are likely multi-factorial and may involve limiting the consequences of chronic adrenergic stimulation on cardiomyocytes, changes in loading conditions and reductions in cardiomyocyte work related in part to reductions in heart rate (HR), indirect systemic systolic blood pressure (BP), left ventricular (LV) contractility and potentially regurgitant volume.7, 8, 9, 10
Carvedilol is a 3rd generation non-selective BB and alpha1-blocker with ancillary antioxidant effects and thus combines the potential benefit of non-selective beta-blockade with the afterload reduction properties of an alpha1-blocker. Additionally, the ancillary antioxidant properties may decrease oxidant stress associated with progressive heart failure.11
The Texas A&M University (TAMU) cardiology service routinely offers clients the option to initiate carvedilol administration once their dog is diagnosed with early or mild preclinical CVD. Dogs with substantial remodeling that are considered to be at imminent risk of CHF are typically excluded from this option. This retrospective review reports the outcome in a case series that had carvedilol initiated for preclinical CVD.
Section snippets
Animals, material and methods
The electronic medical records data base of TAMU Veterinary Medical Teaching Hospital was searched for all canine cases of Stage B CVD that received carvedilol between Jan 2002 and Jan 2011. Fifty dogs with Stage B CVD were identified as having received carvedilol. For the purpose of this study a diagnosis of Stage B1 CVD was defined as the presence of a characteristic murmur in a preclinical dog with a vertebral heart scale (VHS) ≤10.5. Stage B2 CVD was determined by the presence of a
Statistical analysis
Continuous variables are reported as median values, 25th–75th interquartile range (IQR), minimum and maximum value [range]. For each continuous variable, follow-up data are summarized in the same manner as the baseline. Paired baseline to follow-up comparisons were performed using the Wilcoxon matched-pairs signed-ranks test for medians and an exact McNemar’s test for proportions. Parametric survival models including Weibull, exponential and gamma, were evaluated by the use of Akaike’s
Baseline
The baseline study population consisted of 38 dogs. Dogs weighed 8.5 kg (7.6–9.6) [3.0–13.8] and 14/38 (36.8%) were males. The median age of all 38 dogs was 8.6 years (7.2–10.8) [3.0–12.8]. The majority of dogs were CKCS 33/38(86.8%). There was one each of Maltese, Cocker Spaniel, Pomeranian, Miniature Poodle and small mixed-breeds. All dogs had a murmur characteristic of MR and had no current or prior signs or symptoms of CHF. Five of 38 dogs (13.2%) had a VHS ≤10.5 and were categorized as
Discussion
There is emerging interest in evaluation of chronic beta-blockade for the treatment of moderate to severe chronic primary MR in human patients. In one retrospective study the use of beta-blockade was reported to have an independent survival benefit in human patients with chronic severe MR characterized by a normal LV ejection fraction however this has not been substantiated in prospective studies.15 One small pilot study8 reported that short-term treatment (14 days) with a beta-blocker (BB)
Conclusions
This study suggests that carvedilol at an initial dose of 0.31 mg/kg PO twice daily (0.26–0.35; range 0.15–0.53) and a target dose of 1.11 mg/kg twice daily (0.81–1.32; range 0.27–2.02) is safe and well tolerated in dogs with Stage B1 and early Stage B2 (normal LVIDs and LVIDs-N) if an up titration protocol is used that involves a 50–100% increase in dose every 7–14 days until the target dose is reached. Median survival for all dogs was 48.5 months with a 95% CI of 38.3–58.6. This study suggests
Acknowledgments
The authors would like to thank Kathy Glaze for her valuable work on this project.
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