FEBRUARY 2011 • WWW.RHEUMATOLOGYNEWS.COM ARTHRITIS 27 NSAIDs Associated With Cardiovascular Risk

BY SHERRY BOSCHERT loskeletal pain are limited, but cautioned that “cardiovascular risk needs to be tak- Time to Reevaluate NSAIDs FROM BMJ en into account when prescribing” any ach of seven NSAIDs was associ- NSAID. he cardiotoxicity of NSAIDs is are considering NSAIDs for patients ated with significantly increased The meta-analysis included any large, Tparticularly worrisome because at high risk of cardiovascular dis- Erisk for MI, stroke, or death from randomized controlled trials comparing many patients have both cardiovas- ease? Avoid COX-2 inhibitors, espe- cardiovascular disease, compared with any NSAID with other NSAIDs or place- cular disease and musculoskeletal cially in higher doses, Dr. Ray ad- placebo, in the most comprehensive bo. Data were available for naproxen, disease, Wayne A. Ray, Ph.D., noted vised. Avoid diclofenac. Remember meta-analysis of the subject so far. ibuprofen, diclofenac, celecoxib, etori- in an editorial accompanying Dr. that ibuprofen may attenuate the The relative risks with any individual coxib, rofecoxib, and lumiracoxib. The Trelle’s study (BMJ Jan. 11, antiplatelet effects of aspirin. NSAID, compared with placebo, often risk for a cardiovascular event had to in- 2011;342:c6618 [doi:10.1136/bmj. For now, naproxen seems to be were double, triple, or quadruple the risk crease by more than 30% to be consid- c6618]). the safest NSAID in terms of car- with placebo, the study found. The ab- ered significant. What Dr. Trelle’s study adds to diovascular risk. Overall, naproxen appeared the existing literature on NSAIDs is With any NSAID, consider also Major Finding: Each of seven NSAIDs was to be the least harmful NSAID the potentially powerful technique prescribing gastroprotective drugs. VIEW ON THE NEWS associated with significantly increased risk in terms of cardiovascular out- known as network meta-analysis, NSAIDs are not the only option for MI, stroke, or death from cardiovascular comes. Risks were greatest which can extract more informa- for treatment of musculoskeletal disease, compared with placebo. with ibuprofen, diclofenac, tion from the data when certain as- symptoms. Clinicians also prescribe VITALS Data Source: Network meta-analysis of 31 etoricoxib, and lumiracoxib. sumptions are met, compared with paracetamol, low-dose opioid anal- large, randomized controlled trials compar- Four NSAIDs were associat- traditional analyses, he wrote. The gesics, and newer drugs, but without ing any NSAID with other NSAIDs or place- ed with significantly increased strength of the technique is that it large-scale comparison studies, it’s bo in 116,429 patients with 117,218 pa- risk for myocardial infarction uses all of the data, but it has some impossible to tell which is best for tient-years of follow-up. (the primary outcome in the inherent weaknesses that should in- both efficacy and safety, Dr. Ray Disclosures: The Swiss National Science current analysis) in 29 of the tri- spire caution when interpreting es- wrote. “Perhaps it is time for a larg- Foundation funded the study. The investiga- als that reported 554 MIs. The timates based on indirect compar- er, more systematic evaluation of a tors reported having no conflicts of interest. relative risk for MI doubled isons, explained Dr. Ray. broader range of alternatives,” he with rofecoxib or lumiracoxib, For example, no large, placebo- suggested. solute numbers of MIs and other car- was 35% higher with celecoxib, and was controlled trials compared etoricox- diovascular outcomes were small, but 61% higher with ibuprofen, compared ib vs. placebo. Risks of etoricoxib vs. DR. WAYNE A. RAY is a professor and the network meta-analysis design of the with placebo. Evidence was lacking for placebo were estimated based on a director of pharmacoepidem- study “provides the best available evi- increased MI risk with the other three chain of direct comparisons in sep- iology at Vanderbilt University, dence on the safety of this class of NSAIDs. arate trials – etoricoxib vs. di- Nashville, Tenn. Dr. Ray has received drugs,” Dr. Sven Trelle and his associates Among secondary outcomes, stroke clofenac; diclofenac vs. rofecoxib or financial support from Pfizer, was a reported. risk increased with all NSAIDs in 26 tri- celecoxib, and finally rofecoxib or paid expert witness in a lawsuit by the Contrary to some previous reports, als that reported 377 strokes. The in- celecoxib vs. placebo. state of Texas against Merck, and is a the current study also found no sugges- creased risk was significant with four of Based on all the studies, what are paid expert in an insurance company tion that this increased cardiovascular the drugs, roughly doubling with naprox- the best strategies for clinicians who action against the maker of Prempro. risk is specific to cyclo-oxygenase-2 (COX- en and tripling with ibuprofen, di- 2) inhibitors. Therefore the use of all clofenac, etoricoxib, or lumiracoxib, NSAIDs – and the over-the-counter avail- compared with placebo. celecoxib, or lumiracoxib, and increased 28 trials, and the risk of death roughly ability of some of them – should be re- Twenty-six trials reported 312 deaths approximately fourfold with diclofenac doubled with any of the other six NSAIDs. considered, Dr. Trelle stated in a report from cardiovascular disease, accounting or etoricoxib, compared with placebo. Looking at a composite of nonfatal published online by BMJ (Jan. 11, for 46% of all deaths in the trials. All All the NSAIDs were associated with in- MI, nonfatal stroke, or cardiovascular 2011;342:c7086[doi/10.1136/bmj.c7086]). NSAIDs except naproxen were associat- creased risk for death from any cause, death in 30 trials that reported 1,091 Dr. Trelle of the University of Bern, ed with higher risk for cardiovascular compared with placebo, and the increase composite events, the risk increased with Switzerland, acknowledged that thera- death, which increased by 58% with ro- was significant for all except naproxen. all the NSAIDs and increased signifi- peutic options for chronic muscu- fecoxib, roughly doubled with ibuprofen, There were 676 deaths from any cause in cantly with all but naproxen. ■ RA Duration Affects Structural Damage, Inflammation

BY SHARON that earlier treatment tion of 3 years or less, Physical functioning was as- Major Finding: After investigators controlled WORCESTER of these patients with and 507 had a disease sessed using the Health Assess- appropriate therapy for age and sex, Spearman’s correlation co- duration of greater ment Questionnaire (HAQ), FROM THE ANNUAL SCIENTIFIC efficients showed a significant relationship MEETING OF THE AMERICAN prior to development between all measures of physical function- than 3 years. and the Physical Component

COLLEGE OF RHEUMATOLOGY of significant structur- VITALS ing and CRP level in early RA, but no corre- “We pooled data to Score and Physical Functioning al damage should dra- lation between those measures and modi- assess the relationship domain of the Short Form (SF)- ATLANTA – Physical func- matically improve the fied Total Sharp Score (mTSS). In between structural 36 Questionnaire, which assess- tioning in rheumatoid arthritis long-term physical longstanding RA, the measures of physical damage as measured es quality of life, he said. patients is affected more by in- function and disability functioning were significantly correlated by the modified Total Spearman’s correlation coef- flammation early in the disease outcomes of our pa- with mTSS and with CRP. Sharp Score, joint ficients showed a significant re- process, and more by structur- tients with rheumatoid Data Source: From a pooled analysis of space narrowing, and lationship between all three al damage as the disease pro- arthritis,” reported Dr. data from two trials of RA patients. joint erosions. We measures of physical function gresses, according to an analysis Martin J. Bergman. Disclosures: Dr. Bergman disclosed that he also looked at inflam- and C-reactive protein in early of pooled data from two large Dr. Bergman and his has received research grants and consulting mation as measured RA, but no correlation between clinical trials. colleagues studied fees or other remuneration, and/or served on by C-reactive pro- those measures and a modified “We feel that this study con- 1,415 patients from the the speakers bureau for Abbott Laboratories, tein,” said Dr. Total Sharp Score (mTSS). firms that deterioration of phys- two trials, each of Bristol-Meyers Squibb, Roche, and UCB. Bergman, who is both In patients with longstanding ical functioning as a result of which assessed the ef- on the staff of the di- RA, the measures of function RA may be driven predomi- fects of adalimumab in RA: The III trial in patients with early vision of rheumatology at Drex- were significantly correlated nantly by inflammation earlier PREMIER (Prospective Registry RA, and the DE019 trial was a el University in Philadelphia, with mTSS and with CRP – al- in the course of disease, but Evaluating Outcomes After My- randomized, placebo-controlled and chief of the division of though the latter associations over time it is driven more by ocardial Infarction: Events and trial of patients with established rheumatology at Taylor Hospi- were weaker than those seen in structural damage than it is by Recovery) trial was a double- RA. A total of 908 patients from tal of Arthritis and Rheumatol- early disease, Dr. Bergman con- inflammation. It also suggests blind, placebo-controlled phase these trials had a disease dura- ogy in Ridley Park, Pa. cluded. ■