An updated study published in this week's PLoS Medicine gives some new information on the cardiovascular risks of non-steroidal anti-inflammatory drugs (NSAIDs) and suggests that among these commonly used drugs, naproxen and low dose ibuprofen are least likely to increase cardiovascular risk whereas diclofenac, even in doses available without prescription, elevates risk.
Using only observational studies (30 case-control studies and 21 cohort studies) because randomised controlled trials have only reported small numbers of cardiovascular events, the authors, Patricia McGettigan (Hull York Medical School, Hull, UK), and David Henry (Institute for Clinical Evaluative Sciences, Toronto, Canada) also found that the new NSAID, etoricoxib, has a high risk of cardiovascular events similar to that of drugs that have been withdrawn because of safety concerns and that new evidence on cardiovascular risk of indomethacin, an older drug, casts doubt on its continued clinical use.
The authors say: "the large sizes of the studies reviewed here, the presence of consistent dose-response relationships, and general agreement with the results of randomised trials give us confidence in the results." They add: "In our view, the results are sufficiently robust to inform clinical and regulatory decisions."
This study highlights the importance of adequately assessing drug safety in clinical trials and in an editorial the PLoS Medicine editors write: "debates continue about the best ways to meaningfully synthesize and interpret data on the possible harmful effects of drugs – for example, how passive surveillance systems (spontaneous reports of suspected adverse reactions) should be improved, whether new drugs should go through a phased launch process with enhanced safety evaluation, and the appropriateness of risk mitigation strategies for drugs with safety concerns."
The editors conclude: "However, these challenges should not detract investigators, regulators, and patients from demanding a higher safety standard for approved drugs. Higher standards will require both greater transparency – in revealing what studies are being conducted and what data have been generated – and greater willingness of funders to support new studies specifically addressing drug safety."
Article by David Henry and colleagues
Funding: No specific funding was received for this study.
Competing Interests: The authors have declared that no competing interests exist.
Citation: McGettigan P, Henry D (2011) Cardiovascular Risk with Non-Steroidal Anti-Inflammatory Drugs: Systematic Review of Population-Based Controlled Observational Studies. PLoS Med 8(9): e1001098. doi:10.1371/journal.pmed.1001098
IN YOUR COVERAGE PLEASE USE THIS URL TO PROVIDE ACCESS TO THE FREELY AVAILABLE PAPER:
http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001098
CONTACT:
Dr Patricia McGettigan
Hull York Medical School
Hull
United Kingdom
+44 7933 271 258.
patricia.mcgettigan@hyms.ac.uk
Deborah Creatura
Media Officer
ICES
Toronto
Canada
+1 416 480 4780
deborah.creatura@ices.on.ca
Editorial from the PLoS Medicine Editors
Funding: The authors are each paid a salary by the Public Library of Science, and they wrote this editorial during their salaried time.
Competing Interests: The authors' individual competing interests are at http://www.plosmedicine.org/static/editorsInterests.action. PLoS is funded partly through manuscript publication charges, but the PLoS Medicine Editors are paid a fixed salary (their salary is not linked to the number of papers published in the journal).
Citation: The PLoS Medicine Editors (2011) Why Drug Safety Should Not Take a Back Seat to Efficacy. PLoS Med 8(9): e1001097. doi:10.1371/journal.pmed.1001097
IN YOUR COVERAGE PLEASE USE THIS URL TO PROVIDE ACCESS TO THE FREELY AVAILABLE PAPER:
http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001097
(This preview lists Emma Veitch as Academic Editor for the submission. Please note that this is an error and there is no Academic Editor for this article.)
CONTACT: medicine_editors@plos.org
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PLoS Medicine