Background/Purpose: Patients with rheumatoid arthritis (RA) are at increased risk for cardiovascular disease (CVD) compared to the general population, both due to classical and novel risk factors. It remains unclear whether primary prevention strategies for CVD are effective in high grade inflammatory conditions such as RA and there are no previous, CVD outcome statin trials in patients with RA. TRACE RA was designed to assess whether atorvastatin 40mg daily is superior to placebo for the primary prevention of CVD events in patients with RA.

Methods: Prospective, randomised, double-blind, placebo-controlled, UK multicentre trial in RA patients aged >50 years or RA duration >10 years; without known atherosclerotic disease, diabetes, myopathy; not taking statins. All patients were given lifestyle advice.  Primary endpoint: a composite of CVD death, non-fatal myocardial infarction, cerebrovascular accident (excl. haemorrhagic stroke), transient ischaemic attack, revascularisation. Secondary endpoints included safety outcomes and lipid changes. The trial was designed to have 80% power at p<0.05 to detect a 32% risk reduction with atorvastatin based on 1.8% annual event rate, using intention to treat analysis. Cox regression stratified by centre, Fisher’s exact test, Mann-Whitney test or Kendall’s tau-b were used for analysis, as appropriate.

Results: Trial duration: August 2007-December 2012.  2986 patients from 102 centres were randomised and followed for a median of 2.53 years (IQR 1.94-3.50), providing 7,908 patient-years of follow-up. Atorvastatin and placebo groups did not differ at baseline for age, sex, weight, BMI, RA duration, activity, severity and seropositivity, blood pressure, lipid and glucose levels, family history of CVD or diabetes. Current smoking was higher in the atorvastatin group (18.4% vs 14.5%, p=0.019) and there were also significant differences in NSAID use, ethnicity and EQ5D. Reduction in LDL-c levels was significantly greater in the atorvastatin group compared to placebo (-1.07 vs – 0.14 mmol/l, p<0.001); the magnitude of LDL-c reduction reflected reported compliance. In the atorvastatin group 24 patients had a CVD event, compared to 36 in the placebo (hazard ratio 0.66, 95% confidence interval 0.39-1.11, p=0.119). After adjustment for baseline differences, compliance and non-study statin use, hazard ratio was 0.54 (0.30-0.99), p=0.045.  Number and type of any reported adverse events were similar: 294(19.7%) in the atorvastatin and 292(19.5%) in the placebo group, p=0.927.  Due to a lower (0.76% pa) than anticipated event rate, the trial was terminated early.  

Conclusion: Treatment with Atorvastatin 40mg daily resulted in significantly greater reduction of LDL-c compared to placebo. The 34% (unadjusted) risk reduction for a major CVD event compared to placebo, although not statistically significant due to early termination of the trial, is in line with the Cholesterol Treatment Trialists’ Collaboration meta-analysis of the effect of statins in other populations.  Statin therapy was safe in patients with RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/trial-of-atorvastatin-for-the-primary-prevention-of-cardiovascular-events-in-patients-with-rheumatoid-arthritis/