Multifactorial intervention to prevent cardiovascular disease in patients with early rheumatoid arthritis: protocol for a multicentre randomised controlled trial

Annemarie Lyng Svensson, Robin Christensen, Frederik Persson, Brian Bridal Løgstrup, Annamaria Giraldi, Christian Graugaard, Ulrich Fredberg, Jesper Blegvad, Tina Thygesen, Inger Marie Jensen Hansen, Ada Colic, Döne Bagdat, Palle Ahlquist, Hanne Slott Jensen, Kim Hørslev-Petersen, Ekta Sheetal, Torben Grube Christensen, Lone Svendsen, Henrik Emmertsen, Torkell Ellingsen, Annemarie Lyng Svensson, Robin Christensen, Frederik Persson, Brian Bridal Løgstrup, Annamaria Giraldi, Christian Graugaard, Ulrich Fredberg, Jesper Blegvad, Tina Thygesen, Inger Marie Jensen Hansen, Ada Colic, Döne Bagdat, Palle Ahlquist, Hanne Slott Jensen, Kim Hørslev-Petersen, Ekta Sheetal, Torben Grube Christensen, Lone Svendsen, Henrik Emmertsen, Torkell Ellingsen

Abstract

Introduction: 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 and analysis: 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).

Ethics and dissemination: 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.

Trial registration number: NCT02246257.

Keywords: RHEUMATOLOGY.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Figures

Figure 1
Figure 1
Trial design, visits and end points. BP, blood pressure; CRP, C reactive protein; CSFQ, Changes in Sexual Functioning Questionnaires; DAS28, disease activity score 28; HAQ, Health Assessment Questionnaire; HbA1c, glycated haemoglobin; LDL, low-density lipoprotein; RA, rheumatoid arthritis; VAS, visual analogue scale.
Figure 2
Figure 2
Cardiovascular treatment algorithm—Stepwise Guideline Intervention ERACORI Study.
Figure 3
Figure 3
Early RA intervention algorithm. BP, blood pressure; CRP, C-reactive protein; CSFQ, Changes in Sexual Functioning Questionnaires; DAS28, disease activity score 28; DMARD, disease-modifying antirheumatic drug; GP, general practitioner; HAQ, Health Assessment Questionnaire; HbA1c, glycated haemoglobin; LDL, low-density lipoprotein; MTX, methotrexate; RA, rheumatoid arthritis; SF-12, short form 12-items health survey; VAS, visual analogue scale.
Figure 4
Figure 4
Classification of death in the trial.
Figure 5
Figure 5
Classification of hospitalisation for planned or acute reasons in the trial. MI, myocardial infarction.

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