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Trial of atorvastatin for the primary prevention of cardiovascular events in patients with rheumatoid arthritis (TRACE RA): A multicenter, randomized, placebo controlled trial

Author

Kitas GD1,2, Nightingale P3, Armitage J4, Sattar N5,6, Belch JJF7, Symmons DPM2,8; TRACE RA consortium. Arthritis Rheumatol. 2019 Apr 15. doi: 10.1002/art.40892. [Epub ahead of print]

Author Information

1 Directorate of Research and Development, The Dudley Group NHS Foundation Trust, Dudley, UK.

2 Arthritis Research UK Centre for Epidemiology, University of Manchester, Manchester.

3 Wolfson Computer Laboratory, University Hospitals Birmingham, Birmingham, UK.

4 Clinical Trial Service Unit, University of Oxford, Oxford, UK.

5 Institute of Cardivascular and Medical Sciences, University of Glasgow, Glasgow.

6 Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.

7 Department of Molecular and Vascular Medicine, University of Dundee, Dundee, UK.

8 NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester NHS Foundation Trust, UK.

Abstract

OBJECTIVE: 

Rheumatoid arthritis (RA) is associated with increased cardiovascular event (CVE) risk. The impact of statins in RA is not established. We assessed whether atorvastatin is superior to placebo for the primary prevention of CVE in RA patients.

METHODS: 

Randomized, double-blind, placebo-controlled trial designed for 80% power at p<0.05 to detect a 32% CVE risk reduction based on an estimated 1.8% per annum (pa) event rate. Patients aged >50 years or with RA duration >10 years; without clinical atherosclerosis, diabetes, or myopathy; received atorvastatin 40mg daily or matching placebo. Primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, transient ischemic attack, or any arterial revascularization. Secondary/tertiary endpoints included plasma lipids and safety.

RESULTS: 

3002 patients (mean age 61 years, 74% female) were followed for a median 2.51 years (IQR 1.90-3.49) [7,827 patient-years] - early termination was due to lower than expected event rate (0.77% pa). Among patients allocated atorvastatin 24/1504 (1.6%) had a primary endpoint, compared with 36/1498 (2.4%) on placebo (hazard ratio 0.66, 95%CI 0.39-1.11, p=0.115); adjusted hazard ratio (0.60, 95%CI 0.32-1.15, p=0.127). At trial end, patients on atorvastatin had 0.77±0.04 mmol/L lower LDL-cholesterol compared to placebo (p<0.0001); CRP (mg/L) was also significantly lower on atorvastatin than placebo (2.59 (0.94-6.08) vs. 3.60 (1.47-7.49) - p<0.0001). CVE risk reduction per mmol/L LDLc reduction was 42% (95%CI -14%-70%). Adverse events in the atorvastatin (298 (19.8%)) and placebo (292 (19.5%)) groups were similar.

CONCLUSION: 

Atorvastatin 40mg daily was safe and resulted in significantly greater reduction of LDLc than placebo in patients with RA. The 40% (adjusted) CVE risk reduction is consistent with the Cholesterol Treatment Trialists' Collaboration meta-analysis of statin effects in other populations.