Oral Rapamycin Therapy in Feline Subclinical Hypertrophic Cardiomyopathy: Results of the RAPACAT Clinical Trial

Abstract: Background - Feline hypertrophic cardiomyopathy (HCM) remains a disease with little therapeutic advancement. Rapamycin modulates the mTOR pathway and prevents or reverses cardiac hypertrophy in rodent disease models. Its use in human renal allograft patients is associated with reduced cardiac wall thickness.

Hypothesis/Objectives - We sought to evaluate the effects of once-weekly, delayed-release (DR) rapamycin over 6 months on echocardiographic, biochemical, and biomarker responses in cats with subclinical, non-obstructive HCM.

Animals - Client-owned cats (n=36) with subclinical HCM

Methods - Cats enrolled in this double-blind, multicenter, randomized, placebo-controlled clinical trial were randomized to low- or high-dose DR rapamycin or placebo. Cats underwent physical examination, quality of life assessment, blood pressure, hematology, biochemistry, total T4, fructosamine, urinalysis, N-terminal pro-brain natriuretic peptide, and cardiac troponin I at baseline, days 60, 120 and 180. Echocardiograms were performed at all time points excluding day 120. Outcome variables were compared using RMANCOVA.

Results - No demographic, echocardiographic or clinicopathologic values were significantly different between study groups at baseline confirming successful randomization. At day 180, the primary study outcome variable, maximum LV myocardial wall thickness at any location, was significantly lower in the low-dose DR rapamycin group compared to placebo (p = 0.01). Oral DR rapamycin was well tolerated in all cats with no significant differences in adverse events between groups.

Conclusions and clinical importance - Results demonstrate that DR rapamycin was well tolerated and may reverse or prevent progressive LV hypertrophy in cats with subclinical HCM. A future pivotal clinical trial is warranted.