Rheumatology Advance Access originally published online on May 23, 2007
Rheumatology 2007 46(7):1209-1210; doi:10.1093/rheumatology/kem126
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LETTERS TO THE EDITOR |
Does cardiovascular risk factor profile influence prescribing of non-steroidal anti-inflammatory drugs in a rheumatoid population?
Department of Rheumatology, Royal Victoria Hospital, Belfast
Correspondence to: D.J. Armstrong. E-mail: oswald17727{at}hotmail.com
SIR, There has been much recent debate on the cardiovascular (CVS) risks associated with the long-term use of traditional non-steroidal anti-inflammatory drugs (tNSAIDs) and selective cyclo-oxygenase 2 inhibitors (coxibs), and particularly whether the increased CVS risk associated with the use of rofecoxib [1] applies equally to the other coxibs and tNSAIDs [2–4]. As discussed in the recent editorial by Singh [5], while the American FDA has taken the clear step of treating the cardiovascular risk of all anti-inflammatories as equal [6], the EMEA and MRHA have not [7, 8]. Careful selection of patients without significant CVS disease or risk factors appears vital, especially in diseases such as rheumatoid arthritis (RA) with an inherent increase in CVS disease [9, 10].
In this study, we asked whether age, disease duration or risk factors for CVS disease influenced use of tNSAIDs and coxibs among RA patients. No distinction was made between initial prescription by a rheumatologist or a general practitioner. We reviewed the charts of 176 RA patients randomly selected from our nurse-led RA cardiovascular risk clinic, noting established risk factors and by data interrogation and telephone interviews with the patients, established an exact record of current and past use of tNSAIDs and coxibs.
176 RA patients (45 male, 131 female, median age 61.0 yrs (IQR 52.3–69.0), median duration of disease 11.5 yrs (4.0–21.0) were assessed. Forty (22.7%) had never taken any NSAID or COX-2, almost all, due to a history of peptic ulcer disease and were generally prescribed codeine-based analgesia instead. Sixty three (35.8%) were currently using a tNSAID, 47 (26.7%) a coxib and 66 (37.5%) were taking no prescribed anti-inflammatory drugs. Of those patients currently receiving tNSAID therapy, 22 (34.9%) had previously taken a coxib but had been ‘switched back’ to a tNSAID following the withdrawal of rofecoxib. Of the patients who had ever taken coxib therapy, 17 had taken rofecoxib, 52 celecoxib and 31 etoricoxib. Patients currently not taking any tNSAID or coxib were significantly older (66.0 yrs (59.5–72.0) vs 60.0 yrs (50.0–66.0) P < 0.01 than those currently using either coxib or tNSAID. They also had greater disease duration.
Risk factors for cardiovascular disease were defined as hypercholesterolaemia, hypertension, diabetes mellitus, family history of CVS disease in a first-degree relative, obesity (BMI > 30), smoking and having had a past history of ischaemic heart disease or stroke. The number of patients possessing each number of risk factors, compared with their present use of any anti-inflammatory drug, tNSAID or coxib is shown in Table 1.
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Patients currently receiving no anti-inflammatory therapy had a higher number of CVS risk factors as compared with those taking either coxibs or tNSAIDs (median 3.0 vs 2.0, P = 0.06). There was, however, no significant difference between coxibs or tNSAID groups in terms of CVS risk, age, disease duration or any individual CVS risk factor.
These results underline the high frequency of cardiovascular risk factors in RA patients and the widespread use of tNSAID and coxibs in this group. The 22 patients in whom a switch back was made from coxibs to tNSAIDs represent a cross-section of the group in terms of CVS risk factors (11 had three or more risk factors, 11 had two or less), suggesting that perceived CVS risk did not always figure in the decision to change medication, even at a time when there was a perception (and indeed advice given from some sources to GPs) that tNSAIDs might be safer than coxibs. Finally, 19 of the 38 patients with four or more CVS risk factors remain on treatment with a tNSAID or coxibs.
Following this audit and in light of current opinion on the CVS risks of tNSAID and coxibs, it has been our practice to re-assess all patients on anti-inflammatory medication at routine reviews. Alternatives, such as codeine-based products, or alterations to doses of disease-modifiying drugs or corticosteroids are considered where appropriate, but entail their own problems with unwanted effects, in both the short and long term. Although we discuss the option of stopping anti-inflammatory medication until clearer guidelines are established (especially in patients who have four or more CVS risk factors), the risk for many remains very small and the quality of life gain significance. As a result, many patients opt to remain on the medication.
DJA has received honoraria from Pfizer and MSD.
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References |
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- Bresalier RS, Sandler RS, Quan H, et al. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Eng J Med (2005) 352:1092–1102.
[Abstract/Free Full Text] - Scheiman JM, Fendrick AM. Practical approaches to minimizing gastrointestinal and cardiovascular safety concerns with COX-2 inhibitors and NSAIDs. Arthritis Res Ther (2005) 7(Suppl 4):S23–9.[CrossRef][Medline]
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- Madhok R, Wu O, McKellar G, Singh G. Non-steroidal anti-inflammatory drugs—changes in prescribing may be warranted. Rheumatology (2006) 45:1458–60.
[Free Full Text] - TMT Review of cardiovascular safety of Celebrex. (January 2005) Page 8 of http://www.fda.gov/ohrms/dockets/dockets/04n0559/04N-0559_emc-00002-01.pdf.
- EMEA press release on non-selective NSAIDS. Accessed 10 January 2007. (2 August 2005) http://www.emea.eu.int/pdfs/human/press/pr/24732305en.pdf.
- MHRA release: ‘Cardiovascular safety of NSAIDs – review of the evidence’. Accessed 10 January 2007. http://www.mhra.gov.uk/home/idcplg?IdcService=GET_FILE&dID=1428&noSaveAs=0&Rendition=WEB.
- Crofford LJ, Breyer MD, Strand CV, et al. Cardiovascular effects of selective COX-2 inhibition: is there a class effect? The International COX-2 Study Group. J Rheumatol (2006) 33:1403–8.[ISI][Medline]
- Armstrong DJ. Celecoxib and CVS risk: lessons from the APC and PreSAP studies. Rheumatology. Epublished on 28 November 2006. doi:10.1093/rheumatology/kel398.
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