pet connection

I spent Thursday at a day-long cardiology workshop in Chicago sponsored by Boehringer Ingelheim, the maker of pimobendan, also known as Vetmedin. As some of you may know, my Cavalier Darcy died two years ago of congestive heart failure caused by mitral valve disease, so I was pleased to be able to attend the presentation of the results of their three-year study on pimobendan’s benefits. Full disclosure: although pimobendan was not approved in the U.S. at the time Darcy’s health started going south (it gained FDA approval several months after she died), we had access to it and it clearly improved her quality of life.

The QUEST–Quality of life and Extension of Survival Time–study was funded by BI but was designed, run and reported by 32 independent cardiologists at 28 different centers in Europe, Canada and Australia (the U.S. was excluded because the drug wasn’t approved here). The researchers retained the right to publish the results, no matter what they were. The study population was 252 dogs, making it the largest veterinary cardiology study ever run. That didn’t sound like many to me, but apparently it’s huge, considering that some canine studies have as few as six or 10 dogs. I noticed that when I was reviewing the roundup of studies on the benefits and drawbacks of spay/neuter surgery compiled by Margaret V. Root Kustritz that was published late last year in the Journal of the AVMA, and it was confirmed by Ruth MacPete, a San Diego veterinarian/pet writer who was also in attendance.

“The large sample size enabled a valid, comprehensive and robust data set,” said Michael O’Grady, DVM, an internal medicine specialist at Ontario Veterinary College at the University of Guelph in Canada, one of the study’s lead investigators and a presenter at the workshop. “It’s the most robust statistical analysis to date of any cardiac study.” Results were published in the September/October 2008 issue of the peer-reviewed Journal of Veterinary Internal Medicine.

CHF caused by MVD most commonly affects older small-breed dogs, including Cavalier King Charles Spaniels, Poodles, Chihuahuas and Dachshunds, as well as some older large-breed dogs. Dogs used in the study were older than 5 years, weighed between 5 and 20 kilograms (11 to 44 pounds), had a moderate to high-intensity heart murmur, showed echocardiographic evidence of mitral valve disease, and had clinical signs of congestive heart failure–difficulty breathing, exercise intolerance, coughing.

The single blinded randomized trial began in October 2003 and ended in October 2006. One group of dogs received pimobendan, while the other received the commonly prescribed benazepril hydrochloride. Owners knew which drug their dog received, but investigators, study monitors and the sponsor did not. Treatment with diuretics and digoxin–standard therapy for heart failure–was permitted throughout the study.

The study had three possible end points: sudden cardiac death, euthanasia as a result of cardiac disease, or treatment failure. At the end of the study, 25 dogs were still alive. Of those, 14 had taken pimobendan. The median survival time for the entire study population was 188 days, meaning that half of all the dogs lived longer than 188 days and half lived fewer than 188 days. Dogs taking benazepril had a median survival time of 140 days, while those on pimobendan had a median survival time of 267 days, an extension of 91 percent.

“Dogs in the study that lived longer had a greater chance of dying from non-cardiac causes,” Dr. O’Grady said.

Not related to the study was a discussion by Sonya Gordon, DVM, assistant professor of cardiology at Texas A&M, about a new test to identify circulating biomarkers that can help to diagnose heart failure in dogs and cats as well as what stage it’s in. One of the difficulties with congestive heart failure is that its signs can be subtle or can come on suddenly. That’s what happened with Darcy. But increases in a hormone called B-type natriuretic peptide (also known as N-terminal pro b-type natriuretic peptide, or NT-proBNP) correlate to the amount of stretch or stress in the ventricle. A test that came out last year measures levels of NT-proBNP and has potential as a screening test for pets that seem healthy but are at risk for heart disease, such as Cavaliers with heart murmurs or Maine Coons, which are prone to hypertrophic cardiomyopathy.

Those test results can also be used to stage the severity of heart disease and titration of heart failure medication such as Lasix, which relieves congestion. Determining the appropriate amount of Lasix for Darcy gave us fits, and trying to reduce it to a level that would return her appetite to normal was ultimately what tipped her over into heart failure. I felt horribly guilty about that until I later interviewed John Rush, a board-certified cardiologist at Cummings School of Veterinary Medicine at Tufts University in Grafton, Massachusetts, just a few weeks before Darcy died. He said it’s often difficult to determine an effective dose.

“If you don’t give enough, then you see more signs of heart failure, which is coughing and shortness of breath. If you give too much, they no longer have signs of cough, difficulty breathing and shortness of breath, but they may become weak, lethargic and have a reduced appetite. They may have a rise in their kidney values–the blood urea nitrogen (BUN) and creatinine–and those are generally reversible in most dogs with a reduction in dose of diuretics. So you’re looking for the dose of furosemide that causes them not to show signs of shortness of breath or difficulty breathing, but is not so much that they become weak and lethargic.”

The last time we took Bella to her cardiologist, I asked whether it was time to start her on pimobendan. She didn’t know if it was recommended for dogs that aren’t yet in heart failure, so I asked again at the workshop. The answer? “We don’t know yet.”

That’s just one of the questions still to be answered. What’s the impact of pimobendan and benazepril used together? Should pimobendan be started before heart failure? Would it delay onset of heart failure? Can it help large-breed dogs? A report on how pimobendan affects quality of life is yet to come. In our experience, it gave Darcy five good months out of six.

The conclusion to the JAVMA article reads:

“This study provides compelling evidence that treatment of small to medium-sized dogs, between 5 and 20 kg body weight, suffering from CHF secondary to MMVD with pimobendan in combination with standard therapy lengthens time to death, euthanasia or treatment failure compared with treatment with benazepril plus standard therapy.”

It’s a start.