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I read with great interest the recently published EULAR recommendations for the management of early arthritis.(1) However, I would like to add a few words of comment regarding the use of analgesicsin patients with cardiovascular (CV) and gastrointestinal (GI) risk
factors. In my opinion the rational choice for such patients is the use ofaspirin combined with a proton-pump inhibitor.
First, both coxibs and traditional NSAIDs should not be prescribed in patients at higher CV risk. On the contrary, there is good evidence that analgesic doses of aspirin (up to 1500mg) are associated with protection
from CV events.(2,3) Furthermore, aspirin dose or its higher lifetime use is not significantly associated with hypertension(4) or renal toxicity.(5,6) Importantly, a recent meta- analysis of 24 randomised controlled trials found no evidence of dose- responsiveness for bleeds
over a wide range of doses (50 to 1500 mg/day).(7) Indeed, aspirin in doses commonly used in practice, seems to have an excellent safety profile.(8)
Second, recent evidence suggest that not only NSAIDs but also acetaminophen can raise cardiovascular risk.(9) High acetaminophen use may also increase the risk of hypertension(4) and a decrease of renal function.(5) Interestingly, increased acetaminophen use has now been linked to increased prevalence of asthma and chronic obstructive pulmonarydisease, and with lowered lung function.(10) Surprisingly, a recent case-control study showed that acetaminophen (>2 g per day) was ssociated
with a greater risk of GI perforation or bleed(11) and one cohort study reported a dose-response relationship between acetaminophen and dyspepsia.(12) It appears that regular use of acetaminophen is also associated with symptoms of severe diverticular disease, particularly bleeding.(13)
Lastly, compelling evidence suggests that both aspirin and other NSAIDs are superior to acetaminophen for improving moderate-to-severe painin patients with osteoarthritis(14,15,16) and rheumatoid arthritis.(17)
Likewise, in acute pain states aspirin provides significant and more rapidanalgesia than acetaminophen.(18)
1. Combe B, Landewe R, Lukas C, Bolosiu HD, Breedveld F, Dougados M, et al. EULAR recommendations for the management of early arthritis: report of a task force of the European Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 2007;66:34-45. Epub 2006 Jan 5.
2. Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ
3. Johnson ES, Lanes SF, Wentworth CE 3rd, Satterfield MH, Abebe BL, Dicker LW.A metaregression analysis of the dose-response effect of aspirin on stroke. Arch Intern Med 1999;159:1248-53.
4. Forman JP, Stampfer MJ, Curhan GC. Non-narcotic analgesic dose andrisk of incident hypertension in US women. Hypertension 2005;46:500-7.
5. Curhan GC, Knight EL, Rosner B, Hankinson SE, Stampfer MJ. Lifetime nonnarcotic analgesic use and decline in renal function in women. Arch Intern Med 2004;164:1519-24.
6. Dubach UC, Rosner B, Sturmer T. An epidemiologic study of abuse of analgesic drugs. Effects of phenacetin and salicylate on mortality and cardiovascular morbidity (1968 to 1987) N Engl J Med 1991;324:155-60.
7. Derry S, Loke YK. Risk of gastrointestinal haemorrhage with long term use of aspirin: meta-analysis. BMJ 2000;321:1183-7.
8. Fries JF, Ramey DR, Singh G, Morfeld D, Bloch DA, Raynauld JP. A reevaluation of aspirin therapy in rheumatoid arthritis. Arch Intern Med 1993;153:2465-71.
9. Chan AT, Manson JE, Albert CM, Chae CU, Rexrode KM, Curhan GC, et al. Nonsteroidal antiinflammatory drugs, acetaminophen, and the risk of cardiovascular events. Circulation 2006;113:1578-87.
10. McKeever TM, Lewis SA, Smit HA, Burney P, Britton JR, Cassano PA. The association of acetaminophen, aspirin, and ibuprofen with respiratory disease and lung function. Am J Respir Crit Care Med 2005;171:966-71.
11. Garcia Rodriguez LA, Hernandez-Diaz S. Relative risk of upper gastrointestinal complications among users of acetaminophen and nonsteroidal anti-inflammatory drugs. Epidemiology 2001;12:570-6.
12. Rahme E, Pettitt D, LeLorier J. Determinants and sequelae associated with utilization of acetaminophen versus traditional nonsteroidal antiinflammatory drugs in an elderly population. Arthritis Rheum 2002;46:3046-54.
13. Aldoori WH, Giovannucci EL, Rimm EB, Wing AL, Willett WC. Use of acetaminophen and nonsteroidal anti-inflammatory drugs: a prospective study and the risk of symptomatic diverticular disease in men. Arch Fam Med 1998;7:255-60.
14. Lee C, Straus WL, Balshaw R, Barlas S, Vogel S, Schnitzer TJ. A comparison of the efficacy and safety of nonsteroidal antiinflammatory agents versus acetaminophen in the treatment of osteoarthritis: a meta-analysis. Arthritis Rheum 2004;51:746-54.
15. Towheed TE, Maxwell L, Judd MG, Catton M, Hochberg MC, Wells G. Acetaminophen for osteoarthritis. Cochrane Database Syst Rev 2006;(1):CD004257.
16. Zhang W, Jones A, Doherty M. Does paracetamol (acetaminophen) reduce the pain of osteoarthritis? A meta-analysis of randomised controlled trials. Ann Rheum Dis 2004;63:901-7.
17. Wienecke T, Gotzsche PC. Paracetamol versus nonsteroidal anti-inflammatory drugs for rheumatoid arthritis. Cochrane Database Syst Rev 2004;(1):CD003789.
18. Seymour RA, Hawkesford JE, Sykes J, Stillings M, Hill CM. An investigation into the comparative efficacy of soluble aspirin and solid paracetamol in postoperative pain after third molar surgery. Br Dent J 2003;194:153-7.
Conflict of Interest:
Dr. Pijak has received speaker fees and travel assistance from Fournier.