Clinical Trials of Angiotensin Receptor Neprilysin Inhibitor (ARNI) Treatments for Canine Heart Diseases.

Angiotensin receptor neprilysin inhibitors (ARNI), sacubitril valsartan sodium hydrate tablets (Enresto tablets), have novel mechanisms for inhibitions of simultaneously neprilysin (NEP) and angiotensin II type 1 receptors via renin-angiotensin-aldosterone system (RAAS). In this study, we report here the effects of ARNI on treatments for dogs with chronic heart diseases that regular cardiovascular therapeutics could not maintain cardiac performance.
We administered Enrestﾂｮ tablets at 0.7-3.3 mg/kg bid PO to 7 dogs, 8-17 years old, (6 with heart failures due to valvular heart diseases and 1 with an arrhythmia). They have were already treated with several drugs such as pimobendan, ARBs, angiotensin-converting enzyme inhibitors (ACEI), furosemide, and isosorbide. Concomitant medications were determined by individual symptoms and ACEIs were excluded.

Two patients suffered from pulmonary edema at late stage of heart failures due to severe valvular dysfunctions. Treatments of Enrest improved the quality of life at 16 and 29 days. One patient with exercise intolerance and respiratory failure was able to walk and had a 48-day improvement in quality of life after treatments with Enrest. The remaining three patients with valvular diseases, two with 30-day follow-up and one with 6-month follow-up, have been still alive with Enrest therapeutics.

In recent years, new drugs for cardiovascular diseases such as ARNI, SGLT2 inhibitors and sGC stimulants have been launched in the medicine. In small animal medicine, mitral valve myxomatous degeneration is a representative heart disease associated with aging, and that exhibiting severe left atrial enlargement, cardiogenic cough and pulmonary edema.

In this trial, we used Enresto tablets in 7 dogs with chronic heart diseases and these treatments enabled　patients to increase life expectancy and significant efficacy. Through the present trials, we suggest that ARNI will be a very effective drug of the treatment for canine chronic heart diseases, because the pharmacological effects could be expected to prolong canine life expectancy, preventing myocardial fibrosis and remodeling. In the future, we expect that early therapeutic intervention using ARNI will be helpful for canine cardiovascular diseases associated with aging.


Angiotensin receptor neprilysin inhibitors
ARNI
Enresto
sacubitril valsartan sodium hydrate
dog
veterinary medicine