Multifactorial intervention to prevent cardiovascular disease in patients with early rheumatoid arthritis: protocol for a multicentre randomised controlled trial.
BACKGROUND
Cardiovascular morbidity is a major burden in patients with rheumatoid arthritis (RA). In this study, we compare the effect of a targeted, intensified, multifactorial intervention with that of conventional treatment of modifiable risk factors for cardiovascular disease (CVD) in patients with early RA fulfilling the 2010 American College of Rheumatology European League Against Rheumatism (ACR/EULAR) criteria.


METHODS
The study is a prospective, randomised, open label trial with blinded end point assessment and balanced randomisation (1:1) conducted in 10 outpatient clinics in Denmark. The primary end point after 5 years of follow-up is a composite of death from cardiovascular causes, non-fatal myocardial infarction, non-fatal stroke and cardiac revascularisation. Secondary outcomes are: the proportion of patients achieving low-density lipoprotein cholesterol <2.5 mmol/L, glycated haemoglobin <48 mmol/mol, blood pressure <140/90 mm  Hg for patients without diabetes and <130/80 mm Hg for patients with diabetes and normoalbuminuria (urinary albumin creatinine ratio <30 mg/g) after 1 year of follow-up and the proportion of patients in each treatment group achieving low RA disease activity after 1 year, defined as a disease activity score C-reactive protein (DAS28-CRP) <3.2 and a DAS28-CRP score <2.6 after 12, 24 and 60 months. Furthermore, all hospitalisations for acute and elective reasons will be adjudicated by the event committee after 12, 24 and 60 months. Three hundred treatment-naive patients with early RA will be randomly assigned (1:1) to receive either conventional treatment administered and monitored by their general practitioner according to national guidelines (control group) or a stepwise implementation administered and monitored in a quarterly rheumatological nurse-administered set-up of behaviour modification and pharmacological therapy targeting (1) hyperlipidaemia, (2) hypertension, (3) hyperglycaemia and (4) microalbuminuria (intervention group).


BACKGROUND
This protocol is approved by the local ethics committee (DK-S-2014007) and The Danish Health and Medicines Authority. Dissemination will occur through presentations at National and International conferences and publications in international peer-reviewed journals.


BACKGROUND
NCT02246257.
Department of Rheumatology, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Denmark.
Annemarie Lyng
AL
Svensson
Musculoskeletal Statistics Unit, Department of Rheumatology, The Parker Institute, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Denmark.
Robin
http://orcid.org/0000-0002-6600-0631
R
Christensen
Steno Diabetes Center, Gentofte, Denmark.
Frederik
http://orcid.org/0000-0001-6242-6638
F
Persson
Department of Cardiology, Aarhus University Hospital, Skejby, Denmark.
Brian Bridal
BB
Løgstrup
Psychiatric Center, Sexological Clinic, Copenhagen University Hospital, Denmark.
Annamaria
A
Giraldi
Department of Clinical Medicine, Center for Sexology Research, Aalborg University, Aalborg, Denmark.
Christian
C
Graugaard
Department of Rheumatology, Diagnostic Centre, Regional Hospital Silkeborg, Denmark.
Ulrich
http://orcid.org/0000-0002-7181-1113
U
Fredberg
Department of Rheumatology, Diagnostic Centre, Regional Hospital Silkeborg, Denmark.
Jesper
J
Blegvad
Department of Rheumatology, Diagnostic Centre, Regional Hospital Silkeborg, Denmark.
Tina
T
Thygesen
Department of Rheumatology, Svendborg Hospital, Svendborg, Denmark.
Inger Marie Jensen
http://orcid.org/0000-0001-7283-9786
IM
Hansen
Department of Rheumatology Sydvestjysk Sygehus, Esbjerg/Varde, Denmark.
Ada
http://orcid.org/0000-0001-9873-4528
A
Colic
Department of Rheumatology Sydvestjysk Sygehus, Esbjerg/Varde, Denmark.
Döne
http://orcid.org/0000-0002-1347-0576
D
Bagdat
Reumaklinik Fyn, Odense, Denmark.
Palle
http://orcid.org/0000-0003-2442-5014
P
Ahlquist
Department of Rheumatology, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Denmark.
Hanne Slott
http://orcid.org/0000-0002-7550-9894
HS
Jensen
Kong Christian X's Gigthospital i Gråsten, Denmark.
Kim
http://orcid.org/0000-0002-5475-7610
K
Hørslev-Petersen
Department of Rheumatology, Odense University Hospital, Odense, Denmark.
Ekta
E
Sheetal
Reumaklinik, Roskilde, Denmark.
Torben Grube
http://orcid.org/0000-0002-6600-0631
TG
Christensen
Reumaklinik, Skanderborg, Denmark.
Lone
L
Svendsen
Reumaklinik, Aabenraa, Denmark.
Henrik
H
Emmertsen
Department of Rheumatology, Odense University Hospital, Odense, Denmark Danbio National Registry, Glostrup University Hospital, Denmark.
Torkell
http://orcid.org/0000-0003-0426-4962
T
Ellingsen
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000419:Albuminuria / Q000517:prevention & control; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000188:drug therapy; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D003718:Denmark; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control; D006949:Hyperlipidemias / Q000517:prevention & control; D006973:Hypertension / Q000517:prevention & control; D000960:Hypolipidemic Agents / Q000008:administration & dosage*; D008077:Lipoproteins, LDL; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012107:Research Design; D012307:Risk Factors; D012720:Severity of Illness Index; D019821:Simvastatin / Q000008:administration & dosage*; D055815:Young Adult
D018501:Antirheumatic Agents; D002097:C-Reactive Protein; D006442:Glycated Hemoglobin; D000960:Hypolipidemic Agents; D008077:Lipoproteins, LDL; D019821:Simvastatin
RHEUMATOLOGY