Emulating the EPIC trial using VetCompass primary-care data: causal effects of pimobendan in UK dogs with grade IV/VI heart murmurs

PMCID: PMC12176212

PMID: 40531835

DOI: 10.1371/journal.pone.0325695

Journal: PloS one

Publication Date: 2025-6-18

Authors: Pegram C, Diaz-Ordaz K, Brodbelt DC, Chang YM, Boswood A, et al.

Key Points

• Pimobendan prescription within 6 months of grade IV heart murmur diagnosis reduced 5-year CHF cumulative incidence by 22.2%
• 5-year survival probability doubled from 9.6% to 19.8% with pimobendan treatment
• Early intervention with pimobendan may provide significant clinical benefits in managing preclinical mitral valve disease

Summary

This groundbreaking veterinary study employed target trial emulation to evaluate pimobendan's effectiveness in dogs with preclinical degenerative mitral valve disease (DMVD), demonstrating the potential of observational data analysis to replicate randomized controlled trial (RCT) findings. By analyzing 928 dogs with grade IV heart murmurs, researchers found that prescribing pimobendan within 6 months of diagnosis significantly reduced the 5-year cumulative incidence of congestive heart failure (CHF) from 56.3% to 34.1%, closely mirroring results from the original EPIC trial.

The study's innovative methodology addressed critical methodological challenges in observational research, including immortal time bias and loss to follow-up. Notably, dogs prescribed pimobendan experienced 311 fewer days of health lost to CHF within 5 years and demonstrated improved survival, with the 5-year survival probability approximately doubling from 9.6% to 19.8%. These findings suggest that early pimobendan intervention at the grade IV murmur stage could represent a clinically meaningful strategy for managing preclinical DMVD in small-breed dogs.