perspec tives COX inhibitors increase the risk of cardiovascular events in patients who receive these drugs for prolonged periods of time at higher doses.2–4 However, we object to the conclusion that any dose of nonselective COX inhibitors increases the risk of infarction and death in a healthy population. We doubt that the data support the contention that the intake of COX-2 selective inhibitors increases the cardiovascular death rate in a healthy elderly population. Such unfounded allegations may lead to dangerous decisions, e.g., the substitution of COX inhibitors with opioids for osteoarthrosis, headache, and posttrauma pain.5 Conflict of Interest K.B. is a speaker for Bayer, GSK, Merck, Novartis, Pfizer, and Sanofi. B.R. has received research support from MSD Sharp & Dohme and GSK. © 2009 ASCPT
1. Fosbøl, E.L. et al. Risk of myocardial infarction and death associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) among healthy individuals: a nationwide cohort study. Clin. Pharmacol. Ther. 85, 190–197 (2009). 2. Bresalier, R.S. et al. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N. Engl. J. Med. 352, 1092–1102 (2005). 3. Solomon, S.D. et al. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N. Engl. J. Med. 352, 1071–1080 (2005). 4. Kearney, P.M., Baigent, C., Godwin, J., Halls, H., Emberson, J.R. & Patrono, C. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ 332, 1302–1308 (2006). 5. Shorr, R.I., Griffin, M.R., Daugherty, J.R. & Ray, W.A. Opioid analgesics and the risk of hip fracture in the elderly: codeine and propoxyphene. J. Gerontol. 47, M111–M115 (1992). 1Department of Experimental and Clinical Pharmacology and Toxicology, Friedrich Alexander University of Erlangen–Nuremberg, Erlangen, Germany. Correspondence: K Brune (
[email protected])
Advance online publication 6 May 2009. doi:10.1038/clpt.2009.65
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No Obvious Extra Cardiovascular Risk Associated With Low-Dose NSAIDs N Moore1
5.
To the Editor: The large study by Fosbøl et al. on the risk of myocardial infarction (MI) and death associated with the use of various nonsteroidal anti-inflammatory drugs (NSAIDs)1 seems impressive, but there are many discrepancies, contradictions, and approximations that make it difficult to grasp the real meaning of the results or their validity. 1. Tables 2–4 contain a number of errors that make the data uninterpretable. For example, there are more deaths than combined events for certain drugs and populations. 2. The “healthy” populations are clearly skewed. The authors seem to have eliminated as unhealthy many young women, presumably because they had been hospitalized for childbirth or were prescribed contraceptives. The more strictly selected population B (supposedly even healthier) is older, contains more men, and has twice the death rate of population A! 3. Exposure periods are poorly explained. In Table 2, median treatment exposure to low-dose ibuprofen is given as 14 days, whereas the total exposure time (98,893 person-years in 301,001 persons) yields a mean exposure time of 120 days. Is this because of some very long treatments or repeated short treatment episodes? Values for different drugs vary from 59 to 120 days—inconsistent with reported exposure in the same population in another report2 and with other studies. What is the median delay between exposure to NSAIDs and death (see comment 7)? 4. Most outcomes are unspecifiedcause death. MIs account for
