By Michael Crawford, MD, Editor
Professor of Medicine, Chief of Clinical Cardiology, University of California, San Francisco
Dr. Crawford reports no financial relationships relevant to this field of study.
SYNOPSIS: A controlled trial that included patients with arthritis on nonsteroidal anti-inflammatory drug (NSAID) therapy who were randomized to continuing NSAIDs or switching to celecoxib showed that cardiovascular and gastrointestinal event rates are low and not different on the two therapies.
SOURCE: MacDonald TM, Hawkey CJ, Ford I, et al. Randomized trial of switching from prescribed non-selective non-steroidal anti-inflammatory drugs to prescribed celecoxib: The Standard care vs. Celecoxib Outcome Trial (SCOT). Eur Heart J 2017;38:1843-1850.
COX-2 inhibitors such as celecoxib have a lower risk of bleeding events than nonsteroidal anti-inflammatory drugs (NSAIDs) but have been associated with higher risks of cardiovascular (CV) events.
However, celecoxib is more potent for relieving symptoms in patients with arthritis. Investigators from Europe conducted the Standard Care vs. Celecoxib Outcome Trial, a prospective, randomized, open-label, blinded outcome evaluation study designed to compare CV and gastrointestinal (GI) safety of continuing NSAIDs compared to switching to celecoxib in patients with osteoarthritis or rheumatoid arthritis.
The patients were > 60 years of age and free from significant CV disease. The primary endpoint was the composite of acute coronary syndrome, stroke, or CV death. Between 2008 and 2013, 7,297 patients across nine trial centers in three countries and 706 primary care practices were randomized and followed for a median of three years. Osteoarthritis was present in 94%. About 70% were taking either diclofenac or ibuprofen. The primary endpoint occurred in 278 patients (4%): 125 on celecoxib and 124 on NSAIDs, which was statistically non-inferior for celecoxib CV outcomes. More serious GI adverse events were reported on NSAIDs (1.8 vs. 1.0%; P = 0.007), but more patients on celecoxib withdrew from treatment (51% vs. 30%; P < 0.0001).
The most common reason for withdrawal from celecoxib treatment was lack of efficiency (23%). The mortality rate was not significantly different between the two therapies (35 celecoxib patients vs. 41 NSAID patients).
The authors concluded that in patients > 60 years of age who were free from CV disease and taking NSAIDs for arthritis, there was no advantage in switching to celecoxib.
This study has three important conclusions. First, GI and CV event rates on NSAIDs or celecoxib were low. Second, CV and GI event rates were not significally different between the two therapies. Third, serious adverse events also were not different between the two therapies. In fact, CV event rates were lower than expected overall (0.9%) compared to an expected rate of > 2% in older subjects without overt CV disease, but many with risks factors for it.
Prior studies reporting higher CV event rates on celecoxib were either observational or randomized, controlled trials of short duration. Also, since these prior studies, CV event rates in Europe and the United States have been decreasing, perhaps because of better risk factor control and other prophylactic therapy. Additionally, concomitant proton pump inhibitor therapy has been recommended for those on long-term NSAIDs, and 38% of the subjects in this trial took them. This may explain the low evidence of GI side effects. However, the doses of all study drugs were relatively low compared to the doses used in previous studies and those recommended for osteoarthritis therapy.
There are several caveats. Enrollment was slower than anticipated, perhaps because of the adverse publicity about NSAIDs and COX-2 inhibitors regarding CV events. Consequently, the investigators had to extend the duration of the study to achieve adequate power for the outcomes of interest. Also, withdrawal rates were high, especially for those on celecoxib.
The most common reason for stopping celecoxib was lack of efficiency. This could be because of the relatively low doses deployed (mean 170 mg per day compared to the minimum recommended dose of 200 mg daily). However, the withdrawal rates were similar to rates seen in other studies. Thus, there is no compelling reason to routinely switch patients with arthritis from NSAIDs to celecoxib.