Big data from VetCompass reaffirms value of Pimobendan in management of canine heart disease
A new VetCompass study from the 91做厙 (91做厙) has confirmed the findings of previous studies, showing positive outcomes for pimobendan treatment in dogs with heart disease. The results – using a successful application of “target trial emulation,” – showed pimobendan prescription within six months of a newly diagnosed grade IV/VI heart murmur in dogs delayed the onset of congestive heart failure (CHF) and improved survival compared to not prescribing the medication.
The study mirrors the findings of the landmark Evaluation of Pimobendan in Cardiomegaly (EPIC) trial conducted by the 91做厙. That randomised controlled trial (RCT) previously demonstrated benefits of pimobendan in dogs with preclinical degenerative mitral valve disease (DMVD) (Boswood et al., 2016). DMVD affects approximately 1 in 28 dogs in England, with Cavalier King Charles Spaniels, King Charles Spaniels, Whippets, Poodles and Yorkshire Terriers at greatest risk (Mattin et al., 2015).
However, it is difficult to carry out RCTs in veterinary medicine due to financial, time, and ethical constraints. Consequently, to solve this serious issue, the VetCompass team undertook a ground-breaking new approach. This replicated the same structure as a RCT but used real-world, anonymised clinical records from more than 100,000 dogs under first opinion veterinary care in the UK in 2016.
The original EPIC trial, a multicentre, double-blinded, placebo-controlled study, found that pimobendan significantly delayed the onset of CHF and improved survival in dogs with stage B2 DMVD. Specifically, pimobendan extended the median time to a composite endpoint of CHF, cardiac-related death, or euthanasia by 462 days - with median overall survival 1,059 days in treated dogs compared to 902 days in untreated dogs.
The VetCompass study aimed to emulate aspects of the EPIC trial. Specifically, the new study aimed to determine whether pimobendan prescription within six months of first detecting a grade IV/VI heart murmur in dogs led to a delay in CHF or cardiac-related death and a longer time to death, compared with no pimobendan prescription.
The new emulated trial included a sample of 928 dogs with an adult bodyweight ≤ 15kg and > six years of age on 1st January 2016. Of these, 178 (19.2%) dogs were prescribed pimobendan within six months of first grade IV murmur diagnosis and 750 (80.8%) dogs were not prescribed pimobendan within six months of first grade IV murmur diagnosis. In the analysis, complex statistical methods balanced the two groups for a range of other differences between the groups including age, breed, insurance status, chronic comorbidities, diagnostic tests performed and veterinary group. This effectively meant that the only difference between the two groups was that one group was prescribed pimobendan, while the other was not.
Dogs prescribed pimobendan had a median age of 9.9 years - younger than the median age of dogs not prescribed pimobendan (10.6 years). After adjustment to balance this difference, the key study findings included:
- Risk of CHF at five years was 34.1% in dogs prescribed pimobendan, compared to 56.3% in dogs not prescribed pimobendan.
- Survival at five years was 19.8% in dogs prescribed pimobendan, compared to 9.6% in dogs not prescribed pimobendan.
- Dogs prescribed pimobendan had 311 fewer days of health lost to CHF within five years.
- Adjusted mean survival time was 1,051 days in dogs prescribed pimobendan versus 905 days in dogs not prescribed pimobendan.
This study is ground-breaking for two main reasons. Firstly, by demonstrating that target trial emulation can replicate findings from RCTs, this opens the door to more of these VetCompass ‘RCTs’ that can help shape the future of evidence generation within veterinary research. And secondly, from a clinical perspective, the current findings suggest that the presence of a grade IV murmur in dogs with a presumed diagnosis of preclinical DMVD may offer an appropriate point at which to begin pimobendan therapy.
Study authors Dr Camilla Pegram, Lecturer of Veterinary Epidemiology at the 91做厙, and Dr Dan O’Neill, Associate Professor of Companion Animal Epidemiology at the 91做厙, said:
“This study showcases how target trial emulation within VetCompass can generate robust, clinically meaningful evidence, particularly in situations where randomised controlled trials ma