BMJ 2015;350:h1186 doi: 10.1136/bmj.h1186 (Published 3 March 2015)
Page 1 of 2
Research News
RESEARCH NEWS True risks of paracetamol may be underestimated, say researchers Jacqui Wise London
A systematic review of paracetamol’s efficacy and tolerability in individual conditions is necessary because the true risks of taking the drug may have been underestimated, a UK team of researchers writes in the Annals of the Rheumatic Diseases.1
Philip Conaghan, professor at the Leeds Institute of Rheumatic and Musculoskeletal Medicine, and colleagues carried out a systematic literature review to assess the adverse event profile of paracetamol. All of the eight studies that met the inclusion criteria were cohort studies. The researchers found a dose related link between paracetamol and increasing incidence of mortality and cardiovascular, gastrointestinal, and renal adverse events, although the overall risks of these problems remained small. Of two studies that showed mortality one found a dose response and reported an increased relative rate of mortality from 0.95 (95% confidence interval 0.92 to 0.98) to 1.63 (1.58 to 1.68) for increasing standard doses of paracetamol when comparing patients who had had paracetamol prescribed with those who had not.
Of four studies that reported cardiovascular adverse events all showed a dose response, and one reported an increased risk ratio of all cardiovascular adverse events from 1.19 (0.81 to 1.75) to 1.68 (1.10 to 2.57). One study showing gastrointestinal adverse events reported a dose response with increased relative rate of adverse events or bleeds from 1.11 (1.04 to 1.18) to 1.49 (1.34 to 1.66). Finally, of four studies showing renal adverse events three reported a dose response—one reporting a change in the estimated glomerular filtration rate from 1.40 to 2.19. The main limitations of the research are the low number of studies and the quality of the available evidence. All of the studies were observational, and people who need long term paracetamol often have multiple medical problems that need other analgesics and drugs.
epidemiology at Queen Mary University of London, said, “There are a number of reasons why the authors’ conclusions should be treated with caution; whilst they acknowledge limitations in their paper I found the press release (which contains some ‘cherry picked’ results) a little misleading. “Firstly, the UK mortality study had two main limitations: this cohort study only looked at data for prescribed paracetamol, whereas we know most paracetamol is bought and taken without prescription. Also, there was limited information about the people taking the paracetamol and their health, which meant there were confounding factors that couldn’t be accounted for in the analysis. “Secondly, the Danish mortality study concluded that associations between paracetamol use and a variety of causes of death were largely explained by ‘confounding by indication,’ which means that the apparent link between long term paracetamol use and these health outcomes may be more likely to be explained by the conditions or symptoms for which the paracetamol is being taken.
“Thirdly, the majority of the studies showed similar associations with ibuprofen (e.g. findings for cardiovascular disease and hypertension), so the results were not specific for paracetamol. “And fourthly, the authors do not discuss mechanisms by which paracetamol might be causally linked to the diverse outcomes studied.”
Shaheen concluded, “Given these limitations, this systematic review does not strengthen the weak evidence for harmful causal effects of paracetamol suggested by the component cohort studies. However, further rigorous research into possible detrimental effects of this commonly used drug would be prudent.”
“Every prescribing decision involves a calculation of risk versus benefit, a trade-off of efficacy versus tolerability,” the researchers wrote. “However, when analgesic benefit is uncertain, as has been recently suggested for paracetamol in the treatment of osteoarthritis joint pain and low back pain, more careful consideration of its usage is required.” They concluded, “Given its high usage and availability as an over-the-counter analgesic, a systematic review of paracetamol’s efficacy and tolerability in individual conditions is warranted.” But one expert said that the article should be treated with caution. Seif Shaheen, clinical professor of respiratory For personal use only: See rights and reprints http://www.bmj.com/permissions
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BMJ 2015;350:h1186 doi: 10.1136/bmj.h1186 (Published 3 March 2015)
Page 2 of 2
RESEARCH NEWS
1
Roberts E, Delgado Nunes V, Buckner S, Latchem S, Constanti M, Miller P, et al. Paracetamol: not as safe as we thought? A systematic literature review of observational studies. Ann Rheum Dis 2015; doi:10.1136/annrheumdis-2014-206914.
For personal use only: See rights and reprints http://www.bmj.com/permissions
Cite this as: BMJ 2015;350:h1136 © BMJ Publishing Group Ltd 2015
Subscribe: http://www.bmj.com/subscribe
Page 1 of 2
Research News
RESEARCH NEWS True risks of paracetamol may be underestimated, say researchers Jacqui Wise London
A systematic review of paracetamol’s efficacy and tolerability in individual conditions is necessary because the true risks of taking the drug may have been underestimated, a UK team of researchers writes in the Annals of the Rheumatic Diseases.1
Philip Conaghan, professor at the Leeds Institute of Rheumatic and Musculoskeletal Medicine, and colleagues carried out a systematic literature review to assess the adverse event profile of paracetamol. All of the eight studies that met the inclusion criteria were cohort studies. The researchers found a dose related link between paracetamol and increasing incidence of mortality and cardiovascular, gastrointestinal, and renal adverse events, although the overall risks of these problems remained small. Of two studies that showed mortality one found a dose response and reported an increased relative rate of mortality from 0.95 (95% confidence interval 0.92 to 0.98) to 1.63 (1.58 to 1.68) for increasing standard doses of paracetamol when comparing patients who had had paracetamol prescribed with those who had not.
Of four studies that reported cardiovascular adverse events all showed a dose response, and one reported an increased risk ratio of all cardiovascular adverse events from 1.19 (0.81 to 1.75) to 1.68 (1.10 to 2.57). One study showing gastrointestinal adverse events reported a dose response with increased relative rate of adverse events or bleeds from 1.11 (1.04 to 1.18) to 1.49 (1.34 to 1.66). Finally, of four studies showing renal adverse events three reported a dose response—one reporting a change in the estimated glomerular filtration rate from 1.40 to 2.19. The main limitations of the research are the low number of studies and the quality of the available evidence. All of the studies were observational, and people who need long term paracetamol often have multiple medical problems that need other analgesics and drugs.
epidemiology at Queen Mary University of London, said, “There are a number of reasons why the authors’ conclusions should be treated with caution; whilst they acknowledge limitations in their paper I found the press release (which contains some ‘cherry picked’ results) a little misleading. “Firstly, the UK mortality study had two main limitations: this cohort study only looked at data for prescribed paracetamol, whereas we know most paracetamol is bought and taken without prescription. Also, there was limited information about the people taking the paracetamol and their health, which meant there were confounding factors that couldn’t be accounted for in the analysis. “Secondly, the Danish mortality study concluded that associations between paracetamol use and a variety of causes of death were largely explained by ‘confounding by indication,’ which means that the apparent link between long term paracetamol use and these health outcomes may be more likely to be explained by the conditions or symptoms for which the paracetamol is being taken.
“Thirdly, the majority of the studies showed similar associations with ibuprofen (e.g. findings for cardiovascular disease and hypertension), so the results were not specific for paracetamol. “And fourthly, the authors do not discuss mechanisms by which paracetamol might be causally linked to the diverse outcomes studied.”
Shaheen concluded, “Given these limitations, this systematic review does not strengthen the weak evidence for harmful causal effects of paracetamol suggested by the component cohort studies. However, further rigorous research into possible detrimental effects of this commonly used drug would be prudent.”
“Every prescribing decision involves a calculation of risk versus benefit, a trade-off of efficacy versus tolerability,” the researchers wrote. “However, when analgesic benefit is uncertain, as has been recently suggested for paracetamol in the treatment of osteoarthritis joint pain and low back pain, more careful consideration of its usage is required.” They concluded, “Given its high usage and availability as an over-the-counter analgesic, a systematic review of paracetamol’s efficacy and tolerability in individual conditions is warranted.” But one expert said that the article should be treated with caution. Seif Shaheen, clinical professor of respiratory For personal use only: See rights and reprints http://www.bmj.com/permissions
Subscribe: http://www.bmj.com/subscribe
BMJ 2015;350:h1186 doi: 10.1136/bmj.h1186 (Published 3 March 2015)
Page 2 of 2
RESEARCH NEWS
1
Roberts E, Delgado Nunes V, Buckner S, Latchem S, Constanti M, Miller P, et al. Paracetamol: not as safe as we thought? A systematic literature review of observational studies. Ann Rheum Dis 2015; doi:10.1136/annrheumdis-2014-206914.
For personal use only: See rights and reprints http://www.bmj.com/permissions
Cite this as: BMJ 2015;350:h1136 © BMJ Publishing Group Ltd 2015
Subscribe: http://www.bmj.com/subscribe
