A multicenter, randomized, placebo‐controlled trial of atorvastatin for the primary prevention of cardiovascular events in patients with rheumatoid arthritis

Kitas, G. D. et al. (2019) A multicenter, randomized, placebo‐controlled trial of atorvastatin for the primary prevention of cardiovascular events in patients with rheumatoid arthritis. Arthritis and Rheumatology, 71(9), pp. 1437-1449. (doi:10.1002/art.40892) (PMID:30983166) (PMCID:PMC6771601)

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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 CVEs in RA patients. Methods: A randomized, double‐blind, placebo‐controlled trial was designed to detect a 32% CVE risk reduction based on an estimated 1.6% per annum event rate with 80% power at P < 0.05. RA patients age >50 years or with a disease duration of >10 years who did not have clinical atherosclerosis, diabetes, or myopathy received atorvastatin 40 mg daily or matching placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, transient ischemic attack, or any arterial revascularization. Secondary and tertiary end points included plasma lipids and safety. Results: A total of 3,002 patients (mean age 61 years; 74% female) were followed up for a median of 2.51 years (interquartile range [IQR] 1.90, 3.49 years) (7,827 patient‐years). The study was terminated early due to a lower than expected event rate (0.70% per annum). Of the 1,504 patients receiving atorvastatin, 24 (1.6%) experienced a primary end point, compared with 36 (2.4%) of the 1,498 receiving placebo (hazard ratio [HR] 0.66 [95% confidence interval (95% CI) 0.39, 1.11]; P = 0.115 and adjusted HR 0.60 [95% CI 0.32, 1.15]; P = 0.127). At trial end, patients receiving atorvastatin had a mean ± SD low‐density lipoprotein (LDL) cholesterol level 0.77 ± 0.04 mmoles/liter lower than those receiving placebo (P < 0.0001). C‐reactive protein level was also significantly lower in the atorvastatin group than the placebo group (median 2.59 mg/liter [IQR 0.94, 6.08] versus 3.60 mg/liter [IQR 1.47, 7.49]; P < 0.0001). CVE risk reduction per mmole/liter reduction in LDL cholesterol was 42% (95% CI −14%, 70%). The rates of adverse events in the atorvastatin group (n = 298 [19.8%]) and placebo group (n = 292 [19.5%]) were similar. Conclusion: Atorvastatin 40 mg daily is safe and results in a significantly greater reduction of LDL cholesterol level than placebo in patients with RA. The 34% CVE risk reduction is consistent with the Cholesterol Treatment Trialists’ Collaboration meta‐analysis of statin effects in other populations.

Item Type:Articles
Additional Information:Supported by Arthritis Research UK (grants 16514 and 19704) and the British Heart Foundation (grant SP/06/001).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Macfarlane, Professor Peter and Sturrock, Professor Roger and Cobbe, Professor Stuart and Siebert, Dr Stefan and Stott J, Professor David and Sattar, Professor Naveed and Lowe, Professor Gordon
Authors: Kitas, G. D., Nightingale, P., Armitage, J., Sattar, N., Belch, J. J. F., Symmons, D. P. M., Kitas, G., Belch, J., Symmons, D., Williams, H., Vasishta, S., Storey, R., Nightingale, P., Bruce, I., Durrington, P., McInnes, I., Sattar, N., Situnayake, D., Struthers, A., Lowe, G., Armitage, J., Fox, K., Haskard, D., Dore, C., Bosworth, A., Kitas, G., Belch, J., Symmons, D., Williams, H., Frenneaux, M., Edwards, C., Emberson, J., Bax, D., Cobbe, S., Stott, D., Sturrock, R., Macfarlane, P., Klocke, R., Pullar, T., Knight, S., Rowe, I., Kumar, P., Goodson, N., Mulherin, D., Brzeski, M., Gardiner, P., Situnayake, D., Walker, D., Callaghan, R., Allen, M., McCarey, D., George, E., Deighton, C., Kirkham, B., Teh, L.‐S., Luqmani, R., Chakravarty, K., Nixon, J., Richards, S., Scott, D., Woolf, T., Prouse, P., Packham, J., Davies, M., DeLord, D., O’Neill, T., Pande, I., Harvie, J., Watts, R., Rankin, E., Papasavvas, G., Emery, P., Sinha, A., Dasgupta, B., Bruce, I., Creamer, P., Zoma, A., Walsh, D., Van‐Laar, J., Capps, N., Cairns, A., Marguerie, C., Kumar, N., Abernethy, R., Lillicrap, M., Ralston, S., Makadsi, R., Hopkinson, N., Tan, S., Akil, M., Ahmad, Y., Adler, M., Bukhari, M., Sanders, P., Roussou, E., Binymin, K., Hassan, A., Hughes, R., O’Reilly, D., Sainsbury, P., Richmond, R., Malgorzata, M., Nisar, M., McEntergart, A., Roy, D., Marks, J., Batley, M., McKenna, F., Irani, M., Harris, H., Smyth, A., Tunn, E., Young, A., Thomas, J., Hall, F., Marshall, T., Rao, C., Baburaj, K., Dixey, J., Gendi, N., Birrell, F., Chelliah, G., Morgan, A., Fishman, D., Knights, S., Coady, D., Makadsi, R., Smith, B., Harrison, B., Walker, D., Siebert, S., Chan, A., Putchakayala, K., Al‐Ansari, A., Gough, A., Naz, S., Kumar, N., Pyne, D., Mahmud, T., Patel, Y., and Isdale, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Arthritis and Rheumatology
Publisher:Wiley
ISSN:2326-5191
ISSN (Online):2326-5205
Published Online:15 April 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Arthritis and Rheumatology 71(9):1437-1449
Publisher Policy:Reproduced under a Creative Commons License

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