August 19, 2014

expert reaction to study investigating two antibiotics and risk of cardiac deaths

A paper in the British Medical Journal reported an association between use of the antibiotic clarithromycin and a small increased risk of cardiac deaths. The authors suggest that more research should be carried out before changing prescription practices. A before the headlines analysis accompanied this roundup.

Prof Kevin McConway, Professor of Applied Statistics, The Open University, said:

“It’s important to realise that the researchers are not calling for clinicians to stop prescribing clarithromycin, but instead for more data from different populations of patients, to see whether or not their finding can be confirmed. They have good reasons for that cautious conclusion.

“One important point is that, even though they studied most of the courses of treatment with these antibiotics in the whole of Denmark for a 15 year period, there still were rather few deaths from heart disease while the drugs were being taken. That tells us two things. First, the risk of such a death when taking one of these antibiotics is very small. Second, even in this huge study, there were too few deaths to get a very precise figure for how much greater the cardiac death rate was on clarithromycin than on penicillin V. On the researchers’ own analysis, the cardiac death rate on clarithromycin could plausibly be anywhere between 8% and 185% higher than the rate on penicillin V. So they concluded that the death rate was higher on clarithromycin, but they couldn’t be very sure how much higher. And in any case a death rate that’s just a bit higher than a very small death rate will still be very small.

“The researchers point out in their paper that they did not have the right data to investigate all the possible differences between the patients on the different drugs, that might affect their chances of death from heart disease. For instance, they had no data on smoking or on obesity – if for some reason the patients on clarithromycin were more likely to be obese, or smoked more, that could explain some of the difference in death rates. Big differences of this sort between the groups might not be very likely, but they would not have to be very big to raise the possibility at least that the death rate is not actually higher on clarithromycin.

“This is, in my view, a good study with good use of statistics. But, because of limitations I’ve mentioned (and others), the researchers rightly don’t go further than calling for further studies to clarify the position. Since in any case the cardiac death rate while on these drugs is very small, this isn’t a risk that I personally would worry about anyway.”

Dr Mike Knapton, Associate Medical Director, British Heart Foundation, said:

“All medications can come with side effects, which is why your doctor will always weigh up the risks before prescribing drugs to patients.

“Health professionals already know to exercise caution when prescribing clarithromycin in patients who have, or may be pre-disposed to Long QT syndrome – a condition that can cause sudden cardiac death. This study shows that they should continue to follow that advice.

“More research is now needed to understand the effect of this antibiotic on the wider population. The bottom line is no one should be taking antibiotics unless they absolutely have to and doctors should give careful consideration before prescribing them. If you are taking clarithromycin at the moment, you should not stop without discussing this further with your GP.”

Dr R Andrew Seaton, Consultant in Infectious Diseases and General Medicine, NHS Greater Glasgow and Clyde Health Board, said:

“This paper looks at two antibiotics that, as well as killing bacteria, are known to prolong the electrical activity of the heart muscle during each beat (the QT interval).  It was already known that clarithromycin should be used with caution in people with conditions that are associated with prolonging the QTc (the QT interval corrected for heart rate) or who are already receiving other drugs which may be associated with prolongation of the QTc (see www.qtdrugs.org).

“The use of clarithromycin along with other drugs which have the potential to inhibit its metabolism (which may in turn potentiate the effect on QTc prolongation) should also be avoided.

“Clarithromycin is used to treat bacterial upper and lower respiratory tract infections.  As we have all heard recently, antibiotics can be overused and may be unnecessarily prescribed – in conditions where antibiotics are required, alternatives to clarithromycin should be considered when other risk factors for QTc prolongation (including clarithromycin metabolism inhibiting drugs, and certain heart conditions) are evident.”

Dr Tim Chico, Reader in Cardiovascular Medicine and consultant cardiologist, University of Sheffield, said:

“It would be a mistake to conclude that this study proves clarithromycin increases the risk of cardiac death. A slightly higher number of patients died while or soon after taking clarithromycin compared with penicillin but this may have been due to other differences between these patients, who the study authors acknowledge were different in several important ways. There are many good reasons to avoid unnecessary use of antibiotics such as trying to reduce development of bacteria that are resistant to treatment but I do not think that this study calls for a change in whether patients are prescribed clarithromycin.”

‘Use of clarithromycin and roxithromycin and risk of cardiac death: cohort study’ by Henrik Svanström et al. published in the BMJ on Tuesday 19 August 2014.

Declared interests

None declared