A Multicenter, Randomized, Placebo‐Controlled Trial of Atorvastatin for the Primary Prevention of Cardiovascular Events in Patients With Rheumatoid Arthritis. Issue 9 (22nd July 2019)

• Record Type: Journal Article
• Authors: Kitas, George D.; Nightingale, Peter; Armitage, Jane; Sattar, Naveed; Belch, Jill J. F.; Symmons, Deborah P. M.
• Other Names: Kitas George investigator.; Belch Jill investigator.; Symmons Deborah investigator.; Williams Hawys investigator.; Vasishta Shobna investigator.; Storey Rebecca investigator.; Nightingale Peter investigator.; Bruce Ian investigator.; Durrington Paul investigator.; McInnes Iain investigator.; Sattar Naveed investigator.; Situnayake Deva investigator.; Struthers Allan investigator.; Lowe Gordon investigator.; Armitage Jane investigator.; Fox Keith investigator.; Haskard Dorian investigator.; Dore Caroline investigator.; Bosworth Ailsa investigator.; Kitas George investigator.; Belch Jill investigator.; Symmons Deborah investigator.; Williams Hawys investigator.; Frenneaux Michael investigator.; Edwards Christopher investigator.; Emberson Jonathan investigator.; Bax Deborah investigator.; Cobbe Stuart investigator.; Stott David investigator.; Sturrock Roger investigator.; Macfarlane Peter investigator.; Klocke Rainer investigator.; Pullar Tom investigator.; Knight Susan investigator.; Rowe Iain investigator.; Kumar Pradeep investigator.; Goodson Nicky investigator.; Mulherin Diarmuid investigator.; Brzeski Micheal investigator.; Gardiner Philip investigator.; Situnayake Deva investigator.; Walker David investigator.; Callaghan Rob investigator.; Allen Margaret investigator.; McCarey David investigator.; George Emmanuel investigator.; Deighton Chris investigator.; Kirkham Bruce investigator.; Teh Lee‐Suan investigator.; Luqmani Raashid investigator.; Chakravarty Kuntal investigator.; Nixon Jenny investigator.; Richards Selwyn investigator.; Scott David investigator.; Woolf Tony investigator.; Prouse Peter investigator.; Packham Jonathan investigator.; Davies Martin investigator.; DeLord Denise investigator.; O'Neill Terence investigator.; Pande Ira investigator.; Harvie John investigator.; Watts Richard investigator.; Rankin Elizabeth investigator.; Papasavvas George investigator.; Emery Paul investigator.; Sinha Arvind investigator.; Dasgupta Bhaskar investigator.; Bruce Ian investigator.; Creamer Paul investigator.; Zoma Asad investigator.; Walsh David investigator.; Van‐Laar Jaap investigator.; Capps Nigel investigator.; Cairns Andrew investigator.; Marguerie Christopher investigator.; Kumar Namita investigator.; Abernethy Rikki investigator.; Lillicrap Mark investigator.; Ralston Stuart investigator.; Makadsi Raad investigator.; Hopkinson Neil investigator.; Tan Su investigator.; Akil Mohammed investigator.; Ahmad Yasmeen investigator.; Adler Matthew investigator.; Bukhari Marwan investigator.; Sanders Paul investigator.; Roussou Euthalia investigator.; Binymin Khalid investigator.; Hassan Alaa investigator.; Hughes Rod investigator.; O'Reilly David investigator.; Sainsbury Paul investigator.; Richmond Ruth investigator.; Malgorzata Magliano investigator.; Nisar Mohammed investigator.; McEntergart Ann investigator.; Roy Dipak investigator.; Marks Jeffrey investigator.; Batley Michael investigator.; McKenna Frank investigator.; Irani Mike investigator.; Harris Helen investigator.; Smyth Anita investigator.; Tunn Eddie investigator.; Young Adam investigator.; Thomas Joegi investigator.; Hall Frances investigator.; Marshall Tarnya investigator.; Rao Chandini investigator.; Baburaj Krishnan investigator.; Dixey Josh investigator.; Gendi Nagui investigator.; Birrell Fraser investigator.; Chelliah Gladstone investigator.; Morgan Ann investigator.; Fishman Daniel investigator.; Knights Sally investigator.; Coady David investigator.; Makadsi Raad investigator.; Smith Bill investigator.; Harrison Beverley investigator.; Walker David investigator.; Siebert Stefan investigator.; Chan Anthony investigator.; Putchakayala Kiran investigator.; Al‐Ansari Atheer investigator.; Gough Andrew investigator.; Naz Sophia investigator.; Kumar Namita investigator.; Pyne Dev investigator.; Mahmud Taher investigator.; Patel Yusaf investigator.; Isdale Amanda investigator.;
• Is Part Of: Arthritis & rheumatology. Volume 71:Issue 9(2019)
• Page Start: 1437
• Page End: 1449
• Publication Date: 2019-07-22
• Subjects: Arthritis -- Periodicals; Rheumatism -- Periodicals; 616.72
• DOI: 10.1002/art.40892
• Languages: English
• ISSNs: 2326-5191

Abstract

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.