Drug's clinical trial success paved way to overprescribing

Despite excellent study results, side effects emerged with wider use of spironolactone. Experts say the experience illustrates the sometimes bumpy path from bench to clinical setting.

By Victoria Stagg Elliott, AMNews staff. Sept. 27, 2004.

Five years after the publication of a large trial that added a medication to the drug regimen of many heart failure patients, physicians are discovering that a good study doesn't necessarily translate into improved outcomes.

"The Randomized Aldactone Evaluation Study (RALES) was very impressive and made a major change in how we were treating heart failure," said Stephen Siegel, MD, a cardiologist and clinical assistant professor of medicine at New York University School of Medicine. "But there are differences between management in an academic, controlled environment and the usual clinical setting."

According to a paper published last month in the New England Journal of Medicine, the NEJM's 1999 publication of RALES did lead to an increase in prescribing of the drug but did not result in the study's 30% decrease in mortality rates. Hospitalization for hyperkalemia, a known side effect of the drug, increased, as did the deaths from this complication. This increase was greater than expected from the uptick in the drug's use.

The paper's authors say that the original trial was excellent and justified changing clinical practice. Still, the chain of events was far from perfect.

"This is a life-saving drug for patients with bad heart failure, and the RALES trial showed us that," said David Juurlink, MD, PhD, lead author of the latest paper and a scientist at the Institute for Clinical Evaluative Sciences in Toronto. "But a couple things went wrong."