Celecoxib, Nonselective NSAID CV Risk Similar in Primary-Care Setting: SCOT Published

Larry Hand

October 13, 2016

DUNDEE, SCOTLAND — In a trial conducted in three European countries, switching arthritis patients with no known cardiovascular disease from conventional nonsteroidal anti-inflammatory drugs (NSAIDs) to the cyclooxygenase-2 (COX-2) inhibitor celecoxib did not provide any advantage to patients in primary care[1].

Cardiovascular events were infrequent and similar between celecoxib and non–COX-selective NSAIDs among patients >60 years old during a median follow-up of 3 years in the Standard Care vs Celecoxib Outcomes Trial (SCOT).

"Our study results suggested that for patients with no history of cardiovascular disease, it is probably acceptably safe to take many of the NSAIDs," senior author Dr Isla Mackenzie (University of Dundee and Ninwells Hospital, Scotland) told heartwire from Medscape.

"In individual patients, the choice of whether to use these drugs will always be a balance of the benefits in terms of symptom control and the possible risks of adverse effects. Patients should be given the information and helped to reach informed decisions in consultation with their physicians," she said.

Lead author Dr Thomas M MacDonald (University of Dundee, Scotland) told heartwire , "I think toxicity is related to where you are on the dose-response curve. Potent NSAIDs equal good pain relief but have a bit more CV toxicity."

The results were published online October 4, 2016 in the European Heart Journal and had been presented in preliminary form at the European Society of Cardiology (ESC) 2015 Congress.

As covered then by heartwire , some observers knocked the SCOT results for being statistically weak, in part due to a low event rate in a cohort at low CV risk to begin with.

Also, when MacDonald presented the results live at the meeting last year, he observed that Pfizer withdrew support after it concluded that there would be no significant difference between the COX-2 inhibitor and the other agents. "It would have been good if this trial had had more patients and follow-up for longer," he said.

The trial entered 7297 patients in the UK, Denmark, and the Netherlands between January 29, 2008 and March 27, 2013 across nine trial centers and 706 primary-care practices. Patients with osteoarthritis or rheumatoid arthritis taking the prescribed NSAIDs diclofenac or ibuprofen were randomized to switch to celecoxib (n=3647) or continue the NSAID (n=3650).

A total of 249 patients experienced 278 CV events included in the primary end point, the composite of hospitalization for nonfatal MI or other biomarker-positive acute coronary syndrome, nonfatal stroke, or CV death. The rates came to 1.14 per 100 patient-years in the intention-to-treat (ITT) analysis for celecoxib patients and to 1.10 per 100 patient-years for NSAID patients (hazard ratio 1.04, 95% CI 0.81–1.33; P=0.75).

Just over half (50.9%) in the celecoxib group withdrew from the randomized therapy and 30.2% of the NSAID group withdrew from therapy (P <0.0001). Of the celecoxib group, 23.3% cited lack of efficacy as the reason, compared with 9.7% for the NSAID group, while 17.3% of celecoxib patients and 14.1% of NSAID patients cited adverse events.

In the on-treatment analysis, 35 patients in the celecoxib group and 41 in the nonselective-NSAID group died (hazard ratio 1.20, 95% CI 0.76–1.88, P<0.43), while 99 deaths occurred in the celecoxib group and 111 occurred in the NSAID group in the ITT analysis (HR 0.92, 95% CI; P<0.56).

More nonserious adverse events occurred in the celecoxib group compared with the NSAID group (22% vs. 16.1%, P<0.001).

"The move to reduce NSAID prescribing has resulted in lots of patients taking opiates. In the US, this has resulted in a lot of problems. NSAIDs seem okay, at least in those without CV disease," MacDonald told heartwire.

"More research should be done into the relative effectiveness of different NSAIDs related to their risks of adverse events, so that patients can make informed choices balancing pain control and relief of symptoms with the risk of adverse events," MacKenzie said.

Pfizer funded the SCOT and reimbursed the University of Dundee for MacDonald's and MacKenzie's time spent on the trial. MacDonald reported honoraria for lectures and consulting fees from NiCox, Novartis, and AstraZeneca related to NSAIDs. Other disclosures are listed in the article.

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