I happened to notice recently a report in a French newspaper of a study just published in the British Medical Journal, a study that had purportedly shown an increased incidence of cardiac death in people who took an antibiotic called clarithromycin. As I had myself taken this drug a couple of times in my life (though not, of course, quite as prescribed, because no one ever takes drugs quite as prescribed), I felt a certain personal interest in the question.
I needn’t have worried because the paper, from Denmark, claimed that the increased risk of cardiac death occurred only while the patient was taking the drug, not afterwards. But the closer I looked at the paper, the more darkness it seemed to shed on what doctors ought to do.
Denmark is a small country with a population of about 5.5 million, but it has the best health records in the world. This means that statisticians are able to churn out comparisons as Danish dairy farmers churn out butter.
The authors (not one of them a clinician) compared the death rates from cardiac disease of people who had taken either penicillin V, clarithromycin, or roxithromycin, both while they were taking it and for 30 days after they had finished taking it. The results of 4,355,309 courses of penicillin, 160,297 course of clarithromycin and 588,988 courses of roxithromycin in Danish adults between the ages of 40 and 74 were compared.
The authors found that the number of cardiac deaths was the same with all three antibiotics in the month after the course was completed, but slightly more than twice as high in those taking clarithromycin as those taking pencicillin V or roxithromycin. The excess of deaths in absolute numbers among those taking clarithromycin was 37 per million courses of clarithromycin. This may sound small, but since clarithromycin is one of the most commonly used antibiotics in the world, it might mean that there are large numbers of avoidable deaths through people taking clarithromycin. At least, this is what the authors suggest.
Unfortunately, matters are much less clear than the above figures might suggest, though the French newspaper took them at face value.
In the first place, the difference in the number of cardiac deaths between clarithromycin and roxithromycin did not achieve statistical significance; in other words there was a more than 5 percent chance that the difference between the outcomes of the two drugs was itself the product of chance.
In the second place, the medical indications for using penicillin V on the one hand, and clarithromycin or roxithromycin on the other, are not the same, though there is a little overlap. The authors tried to correct for this, but could not do so entirely.
If the patient populations of those taking penicillin V and clarithromycin or roxithromycin were not the same, then any conclusions to be drawn from a comparison would be so tentative as to be useless. Incidentally, one of the indications for using clarithromycin is allergy to penicillin.
It is an elementary scientific principle in this context that like should, as far as possible, be compared with like. It was in fact already known that drugs like clarithromycin have cardiac side effects. But what doctors want to know is whether there are safer alternatives to clarithromycin in the conditions for which it is indicated, for which in most cases penicillin V is not. This paper, then, despite the huge numbers of cases involved, is almost useless, adding not so much to knowledge as to confusion.
The principle lesson to be learned is that you should not believe what you read about medicine in the newspapers. On the other hand, everything else in the newspapers is perfectly reliable, the unadorned truth…