"[Heart failure in horses is] just not very common, but when they get it, it’s severe … a lot of times [they] die a terrible death of pulmonary edema, and they basically drown on the fluid in their lungs,” says Dr. Tiago Afonso, a specialist in large animal internal medicine at the Western College of Veterinary Medicine (WCVM).
“There are not a lot of options [available] in horses at the moment.”
Compared to cardiology-focused research targeting dogs and humans, there are very few peer-reviewed research studies that focus on the equine heart. Fortunately, studies recently published by Afonso and other researchers in the past few years have shone some light on important aspects of heart failure management in this species.
Medications such as angiotensin-converting enzyme (ACE) inhibitors are successfully used in treating heart failure in people and dogs. Previous research conducted by Afonso has shown promising results with the ACE inhibitor benazepril in horses. However, this medication is cost-prohibitive in most countries outside of the United States, and there are important knowledge gaps on the effects of ACE-inhibiting drugs in horses.
Now, Afonso’s goal is to test an affordable option to benazepril. He, along with large animal medical resident Dr. Nicole van der Vossen, are investigating two different ACE inhibitor medications and their effects on a marker of heart failure in the horses’ urine.
“If we’re treating horses with heart failure, most of the cases will be due to a leaking valve,” says van der Vossen, whose research is part of her Master of Science (MSc) program.
She adds that veterinary and human surgical specialists can perform surgery to replace leaking valves in people — but that option isn’t available for equine patients.
Instead of replacing the valve, veterinarians can use ACE inhibitors to extend the quality and duration of a horse’s life. ACE inhibitors prevent the creation of angiotensin II, a peptide hormone that causes vasoconstriction and encourages the release of aldosterone (a steroid hormone that regulates salt and water balance in the body) in the bloodstream.
“Those two [angiotensin II and aldosterone] together will increase blood pressure and blood volume, and so you actually compensate for your failing heart,” says van der Vossen.
These compensatory mechanisms work simultaneously — similar to squeezing the tip of a garden hose and opening the water faucet all the way. The water will reach larger distances, but with the faucet pushing more water through the squeezed-up hose, there’s tremendous strain on the system. In the long run, the system will fail.
This scenario is what happens with the heart — a muscle that will become weakened over time. If high concentrations of angiotensin II and aldosterone continue for too long, there will be negative effects on the body.
ACE inhibitors aim to control the effects of these compensatory mechanisms, decreasing the strain that’s placed on the body’s cardiovascular system. While the ACE inhibitor cannot fix the heart failure, it can slow the disease’s progression and help to lengthen a horse’s life.
Unfortunately, ACE inhibitors are quite expensive for Canadian horse owners. Drug therapies can potentially cost thousands of dollars per month, and they are needed for the rest of the horse’s life. Previous research has shown that an ACE inhibitor called benazepril is the most promising medication in managing heart failure in horses. However, the drug is very expensive outside of the United States.
Ramipril, another ACE inhibitor, is more affordable and Afonso believes that it’s the second-best option to benazepril. The two drugs have never been directly compared to one another at equivalent dosages in an equine-focused study.
The WCVM preliminary study will evaluate whether ramipril has similar effects to benazepril on the parameters of interest, when administered at a similar dosage level. Afonso and van der Vossen will compare these two ACE inhibitors, along with a placebo drug (the study’s control), using a treatment protocol with six healthy mares enrolled in the project.
The team will administer the drugs in a randomized order and then compare the drugs’ efficacy by evaluating the horses’ blood and urine samples.
“We want to make sure that benazepril inhibits that enzyme better than water,” says Afonso. “And then we want to make sure that ramipril, the cheaper one [drug], inhibits the enzyme better than water, and as well as benazepril.”
Depending on their results, the researchers may be able to identify ramipril as a promising alternative to benazepril, its more expensive sibling, for managing congestive heart failure in horses.
“I’m hoping that we can prove that ramipril works as well as benazepril, and if we do manage to show significant [positive] results, then I’m very much hoping that we would [be] able to investigate this on more horses,” says van der Vossen.
Jessica Colby of Montmartre, Sask., is a University of Regina journalism student. She worked at the WCVM as a summer research communications intern in 2021.