MANCHESTER, ENGLAND – Results of the Trial of Atorvastatin for the Primary Prevention of Cardiovascular Events in Patients with Rheumatoid Arthritis (TRACE-RA) suggest that daily treatment with atorvastatin may have a primary protective effect on the development of cardiovascular disease in patients with rheumatoid arthritis.

There was a 34% reduction in the primary composite cardiovascular endpoint, which, although not significant, showed a trend for benefit that was similar to that seen with other statin studies in the general population, according to Dr. George Kitas, a consultant rheumatologist and director of research and development at the Dudley (England) Group NHS Foundation Trust.

“The event rate we observed was actually lower than we had calculated on,” Dr. Kitas said in an interview at the British Society for Rheumatology annual conference. The anticipated event rate was 1.8%, but the observed event rate was 0.76%, he explained. As a result, the trial was terminated early as there would not be sufficient events over the planned time course of the trial.

“However, if you correct for a couple of baseline differences, particularly smoking and ethnicity, and also for compliance, the effect on the CVD event rate is actually statistically significant,” Dr. Kitas observed.

He noted that low-density lipoprotein cholesterol (LDL-C) was lowered by a significant 1.07 mmol/L (19.26 mg/dL) in the 1,492 patients randomized to atorvastatin versus a 0.14 mmol/L (2.52 mg/dL) decrease in the 1,492 patients randomized to placebo (P < .001).

Statins are established as a means of both primary and secondary prevention of CVD in the general population, but few patients with RA were included in the seminal statin trials. The aim of TRACE-RA was therefore to look at statins as a possible means for primary prevention in patients with high-grade inflammation such as RA.

TRACE-RA was a prospective, double-blind trial of 2,986 patients with RA aged 50 years or older or who had a disease duration of more than 10 years and who had been recruited at 102 participating centers between 2007 and 2012.

Patients had been randomized to treatment with atorvastatin 40 mg/day or placebo for the primary prevention of cardiovascular events and the median follow-up was 2.53 years, with an overall 7,908 years of patient follow-up. All patients were given lifestyle advice on how to reduce their cardiovascular risk.

The primary endpoint was a composite of CVD death, nonfatal myocardial infarction, cerebrovascular accident (excluding hemorrhagic stroke), transient ischemic attack, hospitalized angina, and coronary and noncoronary revascularization. A total of 33 of these CVD events occurred in 24 atorvastatin-treated patients and 52 events occurred in 36 patients on placebo. Of these, the majority were coronary events.

Adverse event rates in the atorvastatin and placebo arms were a respective 19.7% and 19.5%. “The side effects that were observed in the statin arm were virtually identical to the side effects that were observed in the placebo arm,” Dr. Kitas noted.

“So, what we think we can say from TRACE-RA is firstly that statins are ‘safe’ in people with rheumatoid arthritis. Secondly, that they have virtually identical effects, both in terms of LDL-C reduction and in terms of hard cardiovascular events, as what one would expect with equivalent doses of statins in the general population,” Dr. Kitas said.

“In practical terms, I would suggest that we all assess our patients regularly for their cardiovascular risk and make sure that we do not hesitate to start a statin in those who fulfill criteria according to the relevant national guidelines.”

Commenting on the study, Dr. Ernest Choy of Cardiff University, Wales, said that this is the largest randomized, controlled trial to look at preventing cardiovascular mortality in patients with RA.

“The message is that cardiovascular risk can potentially be reduced by a statin, especially in high-risk patients,” Dr. Choy said, noting that it also “highlights the importance of monitoring for cardiovascular disease.”

TRACE-RA was funded by Arthritis Research UK and the British Heart Foundation. Pfizer UK provided the study medication and an unrestricted grant for the TRACE-RA biobank. Dr. Kitas had no financial conflicts of interest to disclose.


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