The RALES study, published in 1999, concluded that spironolactone reduce mortality in those with severe heart failure (i.e. Class IV failure). Today’s NEJM comes out with a study showing that due to the RALES study, rates of hyperkalemia and mortality from this complication increased. Taking this into account, there were no significant decreases in death from all causes.
The reason for this is that most patients with CHF are concurrently on ace-inhibitors, and the combination of this medication with spironolactone can lead to hyperkalemia.
This trial is a good example of applying clinical trial medicine to the real world. An excerpt from the editorial:
What lessons can we learn from the post-RALES experience reported by Juurlink et al. and others? First, every effort should be made to define the inclusion criteria for clinical trials as broadly, and the exclusion criteria as narrowly, as possible, so that the findings are relevant to the greatest proportion of patients in clinical practice. Second, it behooves the sponsors and leaders of trials to educate physicians about the careful use of the study treatment. For their part, physicians who prescribe the treatment must fully familiarize themselves with the way in which it was used in the trial and with the contraindications, cautions, adverse effects, and drug interactions. Guidelines may need to do more than recommend which treatments should be used; practical guidance on how to use them is also needed. Finally, we need to make more linked data sets, such as those in Ontario, accessible to interested research groups and formal post-marketing surveillance programs.