Take Your Pick: Heart/Stroke or Cancer

"Our study shows that ramipril provides no significant benefit to high-risk kidney transplant patients. We expect that this will change medical practice around the world and spare patients from taking unnecessary and potentially harmful medication."
"These studies will save lives, improve quality of life, and save the health-care system money."
Dean Fergusson, senior researcher, The Ottawa Hospital Research Institute/University of Ottawa

"We've made great strides in kidney transplants. More than 95 percent of transplants work after a year. ... But we have been less effective at improving long-term survival of the transplant patient."
"We've always seen this slow attrition of kidneys that fail for a variety of reasons. That was my interest. How can we improve things so we're not losing kidney transplant function down the road and patients having to go back on dialysis?"
"That's a major change in their quality of life and, in fact, in their survival."
Greg Knoll, lead co-researcher in drug tests, The Ottawa Hospital Research Institute

About 20,000 kidney transplants are done in Canada on an annual basis, five times that number performed in the United States, and "thousands and thousands more around the world", according to Dr. Knoll, who along with his colleague, Dr. Fergusson, both are authors of a study on the effectiveness of certain drugs in transplants, which was published in The Lancet, and Diabetes & Endocrinology, this week.

They were studying the drug ramipril. This is a drug used with success for over two decades, meant to slow the progression of kidney disease and to lower blood pressure of patients at risk of kidney failure. The assumption was made by health professionals that if the drug is useful for non-transplant patients, then it must by inference be seen as a dug that would help transplant patients.

The two researchers were concerned over kidney transplant outcomes. Acknowledging that the transplants make great strides in improving the quality of life for people in kidney failure, the need to take various pills daily to ensure the transplanted kidney will function as it should, and prevent any complications, presented additional problems. The two researchers, through a series of three new studies demonstrated that the drugs' outcomes do not produce the successes they were assumed to be useful for.

In fact, the reverse appears to occur. There are serious side-effects. Of course, there are side-effects whenever drugs are taken; these are potentials for ongoing problems. The side-effects can be minor and they can be major, and not everyone responds the same way to medications. But the doctors showed that some of those side-effects are serious enough to increase risk of death. The series of drug studies were funded by the Canadian Institutes of Health Research.

Dr. Knoll is a kidney transplant specialist. In explaining what motivated them to study the impact of these commonly used drugs, he pointed out that about 80 percent of kidney transplants remain functional by their fifth year; heaving 20 percent that do not. Over the course of the study the two researchers discovered no difference in several key markers of kidney health between those who received the drug ramipril as compared with those who took a placebo.

 "Patients who received ramipril were more likely to experience side-effects, such as low blood counts [anemia], which can contribute to transplant failure and death", explained Dr. Knoll. And of the outcome of yet another study: "We showed, in fact, that this drug was not very effective" in preventing infection in transplant patients, he commented speaking of yet another drug called levofloxacin, often used to prevent infections from a virus related to kidney transplants.

Then another study published in the British Medical Journal  and funded by the pharmaceutical giant Pfizer, looked at a drug known as sirolimus, used to suppress the immune system, to prevent transplant rejection. Immune-suppressing drugs can also elevate the risk of cancer onset. Widely thought that sirolimus, on the market for 15 years, did not do this, the drug was commonly prescribed to transplant patients who already had a higher risk of cancer.

After a large-scale analysis of sirolimus used with about six thousand kidney transplants around the world, the two researchers concluded, while the drug does lower the risk of cancer, "patients who took the drug were 43 percent more likely to die overall" from heart attacks, strokes and infections. “It’s quite astounding that in the last year, we’ve found that three drugs commonly used in kidney transplant patients either don’t work at all, or don’t work nearly as well as we thought. This shows how essential it is to conduct rigorous research to evaluate drug treatments.”