[img_inline align=”right” src=”http://padnws01.mcmaster.ca/images/McKelvie.jpg” caption=”Dr. Robert McKelvie, cardiologist and professor of medicine, and Dr. George Heckman (below), assistant professor of medicine in geriatric medicine, are questioning which patients benefit most from digoxin and what dose is most appropriate. Photos courtesy of FHS.”]McMaster University experts are adding new fuel to the on-going debate about the potential benefits of prescribing the centuries-old drug digoxin for patients suffering from heart failure.

Dr. George Heckman, an assistant professor of medicine in geriatric medicine, and cardiologist Dr. Robert McKelvie, professor of medicine, argue in the current issue (Tuesday, Feb. 27) of the Canadian Medical Association Journal (CMAJ) that a proper randomized controlled trial is needed to settle questions about which patients benefit the most from this drug, and what dose is most appropriate.

Their view is at odds with that of other researchers who say in the same CMAJ issue that digoxin should be considered for all heart failure patients — ahead of other proven therapies.

This conclusion can't be justified by the Digitalis Investigation Group (DIG) trial, the only adequately powered study to date to assess the impact of dioxin on survival in heart failure, Dr. Heckman said.

“They said if you make all sorts of statistical adjustments, it makes sense to use it, and in fact, they say you should be using it before all the other drugs like angiotensin receptor blockers for which there has been a really solid large trial to back it up,” he said. “We said, 'You can't say that because you haven't got the evidence and the evidence you've got isn't solid enough.'”

The DIG study found no significant difference in death rates between patients on digoxin and those on placebo, although those on digoxin were hospitalized less often.

The typical heart failure patient is in their mid-to-late 70s to early 80s, yet patients participating in studies to date average 65 years of age or younger. The drug appears to be more toxic in older patients.

“Before you start using digoxin for everyone, we are arguing you need a randomized controlled trial in patients who are the right age so we really know what we are dealing with,” Heckman said.

The first systemic study showing the benefits of digoxin, also known as digitalis, was reported by the English physician and botanist William Withering in 1785. However, as little as 10 years ago, the first randomized, placebo controlled trial was undertaken on this drug which is derived from the foxglove plant.

As a geriatric specialist, Heckman became interested in understanding more about the drug while diagnosing elderly patients on digoxin who had been referred to him by their family doctor because of the side effects they were experiencing, such as nausea, loss of appetite, confusion and depression.

“No one could find anything wrong, but when we stopped the digoxin, they started eating like a horse,” he explained.

Heckman said physicians are prescribing digoxin as they were taught to use it.

“What we are doing is questioning the rationale for what we are being told to do and maybe it's not based on evidence that is as sturdy as it ought to be,” he said.

McKelvie said proven therapies should continue to be prescribed because evidence supporting their use is more robust.

Although digoxin, which is not on patent, is a much cheaper drug, he said the better approach is to find ways to fund and support the use of drugs that have proven benefit.

“The inability of some heart failure patients to afford the more effective drugs is deplorable, although the ultimate remedy lies in a more equitable distribution of health care resources rather than recommendations of therapies whose evidence is less substantial,” McKelvie said.