NSAID safety concern eased by SCOT trial

Results from a trial assessing cardiovascular risk with NSAIDs and COX-2 inhibitors are reassuring for rheumatologists and their patients but are unlikely to change clinical practice, an expert says.

The Standard care versus Celecoxib Outcome Trial (SCOT) randomised trial of over 7,000 arthritis patients aged over 60 with no history of heart disease found no increased risk of cardiovascular events with long-term use of either NSAIDs or COX-2 inhibitors.

The findings are “strong evidence” for the safety of these medications overall, in light of recent debate about whether COX-2 inhibitors might carry less gastrointestinal risk but more cardiovascular risk compared to non-selective NSAIDs (nsNSAIDs), said Professor Thomas M MacDonald from the University of Dundee in Scotland who presented the results during a HotLine session at the European Society of Cardiology conference last week.

“We found no difference between nsNSAIDs and celecoxib, with low cardiovascular and upper gastrointestinal adverse event rates overall,” he said.

“In our view, it seems unlikely that another trial of nsNSAIDs versus COX2 inhibitors in subjects free from cardiovascular disease will ever be done due to the low event rates in this population.”

However according to some reports the trial wasn’t set up statistically to provide reliably strong results, at least enough to have an effect on clinical practice guidelines.

Pfizer’s decision to pull out of the trial early due to parity between the two types of anti-inflammatory drugs may have complicated interpretation of the trial, it was suggested.

Speaking to the limbic Philip Conaghan Professor of Musculoskeletal Medicine at the Leeds Musculoskeletal Biomedical Research Unit in the UK said the results of the trial are reassuring for rheumatologists and their patients, as it suggests current selection as to whom should have these drugs results in good long-term outcomes.

“The results are unlikely to change clinical practice, as the cardiovascular side-effects identified in previous studies and meta-analyses mean doctor consideration of patient risk before starting such therapy remains essential,” he said.

Latest advice from the TGA states that doctors should avoid using prescription NSAIDs in patients with heart disease and proceed “with caution” in patients with cardiovascular risk factors.

The SCOT trial randomly assigned patients to either continue their nsNSAID or switch to celecoxib. 

None of the patients had “established cardiovascular disease” but many had risk factors – almost half were hypertensive, a third had elevated cholesterol, and a fifth were on statins.

The primary endpoint was a cardiovascular composite of hospitalisation for non-fatal myocardial infarction, hospitalisation for other biomarker positive acute coronary syndrome, non-fatal stroke or cardiovascular death.

The main secondary outcome was hospitalisation or death for upper gastrointestinal ulcer complications such as bleeding, perforation or obstruction.

The study found no significant differences between groups for any of the outcomes, with the cardiovascular outcome occurring in 1.8 % of the celecoxib group and 2.2% of the nsNSAID group (hazard ratio1.12; P=0.50).

Ulcer-related upper gastrointestinal complications were also uncommon in both groups.

Serious adverse reactions occurred at a similar rate (5.2% in the celecoxib group versus 5.8% in the nsNSAID group).

There were significantly more non-serious adverse reactions in the celecoxib group than the nsNSAID group (22% versus 16.1%, P<0.001) and significantly more patients withdrew from celecoxib compared to nsNSAID treatment (50.9% versus 30.2%, P< 0.0001).

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