March 17, 2017

Is ibuprofen killing you?

The Herald story starts off

Commonly bought over-the-counter painkillers including ibuprofen have been linked to a significant increased risk of cardiac arrest.

The research paper is here (but paywalled).

First, it’s important to remember that “significant” in this context means “detectable” rather than “important.” The risk was higher by about 30%, but cardiac arrest is fairly rare.  With ten years of complete data from Denmark (about 5.5 million people) the researchers accumulated 30,000 cardiac arrests: that’s about five cases per ten thousand people per year.

As usual, this is observational data looking at correlations; the harmful effect, if it’s real, is too small to see reliably in clinical trials.  The researchers used a clever study design where they compared use of painkillers in a cardiac-arrest patient both with the same patient at times in the past and with different patients at the same time.  Differences between people that are constant over time (like smoking) will cancel out of the analysis; differences over time that are constant between people (like season) will also cancel out.  The design doesn’t cancel out non-constant factors like starting an exercise programme that leaves your muscles and joints sore.  It’s not unreasonable that a risk difference this small could be explained by confounding factors.

There’s something more important wrong with the story, though. You might wonder how people who have cardiac arrest get asked about their painkiller use. They didn’t; the study used prescription data.  For many of the painkillers, prescription is the only source; in particular, that’s the case for diclofenac (Voltaren), where the apparent risk increase in the study was a bit larger.

Ibuprofen, however, is available over the counter in Denmark, just as it is here. It’s available in fairly small packages, and is labelled for short-term use, just as it is here. Over-the-counter sale is what the story is basically about, but the study didn’t look at over-the-counter use at all.


Thomas Lumley (@tslumley) is Professor of Biostatistics at the University of Auckland. His research interests include semiparametric models, survey sampling, statistical computing, foundations of statistics, and whatever methodological problems his medical collaborators come up with. He also blogs at Biased and Inefficient See all posts by Thomas Lumley »