A Multicenter, Randomized, Placebo-Controlled Trial of Atorvastatin for the Primary Prevention of Cardiovascular Events in Patients With Rheumatoid Arthritis

被引：86

作者：

Kitas, George D. ^{[1
,2
,12
,13
]}

Nightingale, Peter ^{[3
,14
]}

Armitage, Jane ^{[4
]}

Sattar, Naveed ^{[5
,6
]}

Belch, Jill J. F. ^{[7
,8
,9
]}

Symmons, Deborah P. M. ^{[10
,11
,12
]}

Williams, Hawys ^{[12
]}

Vasishta, Shobna ^{[7
]}

Storey, Rebecca ^{[13
]}

Bruce, Ian ^{[12
,60
]}

Durrington, Paul ^{[12
]}

McInnes, Iain ^{[5
]}

Situnayake, Deva ^{[15
,32
]}

Struthers, Allan ^{[7
]}

Lowe, Gordon ^{[5
]}

Fox, Keith ^{[16
]}

Haskard, Dorian ^{[17
]}

Dore, Caroline ^{[18
]}

Bosworth, Ailsa ^{[18
]}

Frenneaux, Michael ^{[19
]}

Edwards, Christopher ^{[20
]}

Emberson, Jonathan ^{[21
]}

Bax, Deborah ^{[22
]}

Cobbe, Stuart ^{[5
]}

Stott, David ^{[5
]}

Sturrock, Roger ^{[5
]}

Macfarlane, Peter ^{[5
]}

Klocke, Rainer ^{[23
]}

Pullar, Tom ^{[24
]}

Tan, Su ^{[24
]}

Knight, Susan ^{[25
]}

Rowe, Iain ^{[26
]}

Kumar, Pradeep ^{[27
]}

Goodson, Nicky ^{[28
]}

Mulherin, Diarmuid ^{[29
]}

Brzeski, Micheal ^{[30
]}

Gardiner, Philip ^{[31
]}

Walker, David ^{[33
,102
]}

Callaghan, Rob ^{[34
]}

Allen, Margaret ^{[35
]}

McCarey, David ^{[36
]}

George, Emmanuel ^{[37
]}

Deighton, Chris ^{[38
]}

Kirkham, Bruce ^{[39
]}

Teh, Lee-Suan ^{[40
]}

Luqmani, Raashid ^{[41
]}

Chakravarty, Kuntal ^{[42
]}

Roussou, Euthalia ^{[42
]}

Nixon, Jenny ^{[43
]}

Richards, Selwyn ^{[44
]}

机构：

[1] Dudley Grp NHS Fdn Trust, Russells Hall Hosp, Stourbridge, England

[2] Res UK Ctr Epidemiol, Manchester, Lancs, England

[3] Univ Birmingham, Birmingham, W Midlands, England

[4] Univ Oxford, Oxford, England

[5] Univ Glasgow, Glasgow, Lanark, Scotland

[6] Oxford Ctr Diabet Endocrinol & Metab, Oxford, England

[7] Univ Dundee, Dundee, Scotland

[8] Ninewells Hosp, Dundee, Scotland

[9] Med Sch, Dundee, Scotland

[10] Univ Manchester, Arthrit Res UK Ctr Epidemiol, Manchester, Lancs, England

[11] Manchester NHS Fdn Trust, NIHR Manchester Biomed Res Ctr, Manchester, Lancs, England

[12] Univ Manchester, Manchester, Lancs, England

[13] Dudley Grp NHS Fdn Trust, Dudley, England

[14] Univ Hosp Birmingham, Birmingham, W Midlands, England

[15] City Hosp, Birmingham, W Midlands, England

[16] Univ Edinburgh, Ctr Cardiovasc Sci, Edinburgh, Midlothian, Scotland

[17] Imperial Coll London, Eric Bywaters Ctr Vasc Inflammat, London, England

[18] Natl Rheumatoid Arthrit Soc, Maidenhead, Berks, England

[19] Univ Aberdeen, Aberdeen, Scotland

[20] Univ Southampton, Southampton, Hants, England

[21] Univ Oxford, Clin Serv Unit, Oxford, England

[22] Univ Sheffield, Sheffield, S Yorkshire, England

[23] Dudley Grp Hosp NHS Trust, Dudley, England

[24] Tayside Univ, NHS Tayside, Hosp NHS Trust, Dundee, Scotland

[25] East Cheshire NHS Trust, Macclesfield, Cheshire, England

[26] Worcestershire Acute Hosp NHS Trust, Worcester, England

[27] NHS Grampian, Aberdeen, Scotland

[28] Aintree Hosp NHS Trust, Liverpool, Merseyside, England

[29] Mid Staffordshire Gen Hosp NHS Trust, Stafford, England

[30] NHS Forth Valley, Laurieston, Scotland

[31] Western Hlth & Social Care Trust, Londonderry, England

[32] Sandwell & West Birmingham NHS Trust, West Bromwich, England

[33] Newcastle Upon Tyne Hosp NHS Fdn Trust, Newcastle Upon Tyne, Tyne & Wear, England

[34] Aneurin Bevan Hlth Board, Caerleon, England

[35] Univ Hosp Coventry & Warwickshire NHS Trust, Coventry, W Midlands, England

[36] North Glasgow Univ, Hosp Div, NHS Greater Glasgow & Clyde, Glasgow, Lanark, Scotland

[37] Wirral Hosp NHS Trust, Birkenhead, Merseyside, England

[38] Derby Hosp NHS Fdn Trust, Derby, England

[39] Guys & St Thomas NHS Fdn Trust, London, England

[40] East Lancashire Hosp NHS Trust, Burnley, Lancs, England

[41] Nuffield Orthopaed Ctr NHS Trust, Oxford, England

[42] Havering & Redbridge Hosp NHS Trust, Romford, Essex, England

[43] Countess Chester Hosp NHS Fdn Trust, Chester, Cheshire, England

[44] Poole Hosp NHS Trust, Poole, Dorset, England

[45] Kings Coll Hosp NHS Trust, London, England

[46] Royal Cornwall Hosp NHS Trust, Truro, England

[47] Hampshire Private Hosp, Basingstoke, Hants, England

[48] Univ Hosp North Staffordshire NHS Trust, Stoke On Trent, Staffs, England

[49] Pontypridd & Rhondda NHS Trust, Pontypridd, M Glam, Wales

[50] East Kent Hosp NHS Fdn Trust, Kent, England

来源：

ARTHRITIS & RHEUMATOLOGY | 2019年 / 71卷 / 09期

关键词：

RISK-FACTORS; MORTALITY; DISEASE; METAANALYSIS; VALIDATION; ROSUVASTATIN; CHOLESTEROL; COMORBIDITY; PERFORMANCE; PREDICTION;

D O I：

10.1002/art.40892

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：1437 / 1449

页数：13

共 47 条

[1] EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update [J].

Agca, R. ;

Heslinga, S. C. ;

Rollefstad, S. ;

Heslinga, M. ;

McInnes, B. ;

Peters, M. J. L. ;

Kvien, T. K. ;

Dougados, M. ;

Radner, H. ;

Atzeni, F. ;

Primdahl, J. ;

Sodergren, A. ;

Jonsson, S. Wallberg ;

van Rompay, J. ;

Zabalan, C. ;

Pedersen, T. R. ;

Jacobsson, L. ;

de Vlam, K. ;

Gonzalez-Gay, M. A. ;

Semb, A. G. ;

Kitas, G. D. ;

Smulders, Y. M. ;

Szekanecz, Z. ;

Sattar, N. ;

Symmons, D. P. M. ;

Nurmohamed, M. T. .

ANNALS OF THE RHEUMATIC DISEASES, 2017, 76 (01) :17-28

[2] Comparison of cardiovascular risk algorithms in patients with vs without rheumatoid arthritis and the role of C-reactive protein in predicting cardiovascular outcomes in rheumatoid arthritis [J].

Alemao, Evo ;

Cawston, Helene ;

Bourhis, Francois ;

Al, Maiwenn ;

Rutten-van Molken, Maureen ;

Liao, Katherine P. ;

Solomon, Daniel H. .

RHEUMATOLOGY, 2017, 56 (05) :777-786

[3]

[Anonymous], CARD DIS RISK ASS RE

[4]

[Anonymous], 2017, BMJ

[5] Atherosclerosis is not accelerated in rheumatoid arthritis of low activity or remission, regardless of antirheumatic treatment modalities [J].

Arida, Aikaterini ;

Protogerou, Athanasios D. ;

Konstantonis, George ;

Fragiadaki, Kalliopi ;

Kitas, George D. ;

Sfikakis, Petros P. .

RHEUMATOLOGY, 2017, 56 (06) :934-939

[6] THE AMERICAN-RHEUMATISM-ASSOCIATION 1987 REVISED CRITERIA FOR THE CLASSIFICATION OF RHEUMATOID-ARTHRITIS [J].

ARNETT, FC ;

EDWORTHY, SM ;

BLOCH, DA ;

MCSHANE, DJ ;

FRIES, JF ;

COOPER, NS ;

HEALEY, LA ;

KAPLAN, SR ;

LIANG, MH ;

LUTHRA, HS ;

MEDSGER, TA ;

MITCHELL, DM ;

NEUSTADT, DH ;

PINALS, RS ;

SCHALLER, JG ;

SHARP, JT ;

WILDER, RL ;

HUNDER, GG .

ARTHRITIS AND RHEUMATISM, 1988, 31 (03) :315-324

[7] Prediction of cardiovascular risk in rheumatoid arthritis: performance of original and adapted SCORE algorithms [J].

Arts, E. E. A. ;

Popa, C. D. ;

Den Broeder, A. A. ;

Donders, R. ;

Sandoo, A. ;

Toms, T. ;

Rollefstad, S. ;

Ikdahl, E. ;

Semb, A. G. ;

Kitas, G. D. ;

Van Riel, P. L. C. M. ;

Fransen, J. .

ANNALS OF THE RHEUMATIC DISEASES, 2016, 75 (04) :674-680

[8] Performance of four current risk algorithms in predicting cardiovascular events in patients with early rheumatoid arthritis [J].

Arts, E. E. A. ;

Popa, C. ;

Den Broeder, A. A. ;

Semb, A. G. ;

Toms, T. ;

Kitas, G. D. ;

van Riel, P. L. ;

Fransen, J. .

ANNALS OF THE RHEUMATIC DISEASES, 2015, 74 (04) :668-674

[9] Low disease activity (DAS28≤3.2) reduces the risk of first cardiovascular event in rheumatoid arthritis: a time-dependent Cox regression analysis in a large cohort study [J].

Arts, Elke E. A. ;

Fransen, Jaap ;

Den Broeder, Alfons A. ;

van Riel, Piet L. C. M. ;

Popa, Calin D. .

ANNALS OF THE RHEUMATIC DISEASES, 2017, 76 (10) :1693-1699

[10] Risk of Cardiovascular Mortality in Patients With Rheumatoid Arthritis: A Meta-Analysis of Observational Studies [J].

Avina-Zubieta, J. Antonio ;

Choi, Hyon K. ;

Sadatsafavi, Mohsen ;

Etminan, Mahyar ;

Esdaile, John M. ;

Lacaille, Diane .

ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH, 2008, 59 (12) :1690-1697

← 1 2 3 4 5 →