Clinical trial NCT01389388: Effects of Rosuvastatin on Carotid Artery Plaques in Patients With Inflammatory Joint Disease
Official title: Cholesterol Plaques in Carotid and Coronary Arteries and the Effect of Rosuvastatin in Rheumatoid Arthritis, Ankylosing Spondylitis and Other Inflammatory Joint Diseases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Carotid Artery Plaque
Ankylosing Spondylitis
Rheumatoid Arthritis
Keywords: Carotid plaques
inflammatory joint disease
statins
inflammation
lipoprotein components
Lead sponsor: Diakonhjemmet Hospital
Sponsor class: OTHER
First posted: 2011-07-08
Enrollment: 114
Sex: ALL
Minimum age (years): 35
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP

Brief summary: Patients with rheumatoid Arthritis (RA) and Ankylosing Spondylitis (AS) are at greater risk of developing cardiovascular disease. The reason(s) for this have not been well investigated, but there is a general understanding that systemic inflammation plays a part in the increased cardiovascular morbidity and mortality. In spite of the increased risk in these patients, they have not been included as a high risk patient group in cardiovascular prevention guidelines.

The investigators have carried out a cardiovascular study of RA and AS patients, as well as patients with arthritis for the first time. The investigators have demonstrated cholesterol plaques in the carotid artery in some of these patients. Plaques in the carotid artery represent a risk for development of cerebral stroke and are significantly associated with myocardial infarction. These plaques, which are asymptomatic and do not cause haemodynamically significant narrowing, diameter reduction (i.e. operation is not indicated), are vascular atheromatous disease. Therefore, according to prevailing cardiovascular guidelines (SCORE 2007), these patients shall have secondary prevention with a lipid lowering agent with the LDL-cholesterol goal of 1.8 mmol/L and HDL-cholesterol \> 1.0 mmol/L for men and \> 1.1 mmol/L for women.

Statins are cholesterol-lowering drugs, and have been shown to reduce the risk of cardiovascular disease significantly. In addition, reduction in the size of coronary plaques has been induced by statins, when the LDL has been reduced to 1.6-1.8 mmol/l. Plaques in the carotid or coronary arteries have not previously been treated and characterized in patients with RA, AS and other inflammatory forms of arthritis.

The aim of this study is to treat patients with cholesterol plaques in the carotid artery with cholesterol-lowering medication, in the form of Rosuvastatin for 18 months, and characterize the effects on the plaques in the carotid and coronary arteries. In addition, the investigators want to clarify the connection between plaques in the carotid and coronary arteries in patients with RA, AS and other inflammatory forms of arthritis.


Eligibility criteria: Inclusion Criteria:

1. Women and men with RA, AS and other inflammatory forms of arthritis, aged 35-80 years.
2. Cholesterol plaques demonstrated in carotid artery by ultrasound.
3. Informed consent.

Exclusion Criteria:

1. Concomitant statin treatment
2. Arterial fibrillation or others with chronic irregular heart rhythm (because of CT).
3. Contraindication to statin treatment.

   * Hypersensitivity to statins
   * Liver disease with ASAT/ALAT ≥ twice the upper normal limit
   * Previous statin-induced myopathy or severe hypersensitivity reactions to other statins
   * Raised creatinine (because of contrast medium)
   * Pregnancy or breast feeding
   * Fertile women who do not use contraceptives
   * Cyclosporine treatment
   * Treatment with medicinal products that have a known interaction with Rosuvastatin
   * Uncontrolled hypothyroidism defined as TSH \> 1.5 times ULN at the first visit (because of the connection between myopathy and hypothyroidism with statin treatment)
   * Creatinine clearance \< 30 ml/min and \<60 ml/min with a Rosuvastatin dose of 40 mg per day
4. Secondary hyperlipidemia

   * Primary hyperthyroidism
   * Nephrotic syndrome, creatinine \> 2 mg/dl
   * Uncontrolled diabetes mellitus (HbA1C \> 10 %)
   * Plasma Triglycerides \> 6.8 mmol/l
5. Other diseases or treatment that reduces the safety, or treatment with Rosuvastatin which would interfere with the end points of the study

   * Heart failure: NYHA class III B/IV
   * Haemodynamically significant valve defects
   * Established statin treatment
   * Gastrointestinal disease/treatment that can give malabsorption of Rosuvastatin
   * Cancer
   * Severe psychiatric disease
   * Life-threatening ventricular arrhythmias
   * Other medication that increases the risk of rhabdomyolysis
   * Known abuse of alcohol
   * Participation in other studies

Primary outcomes:
measure: Carotid artery cholesterol plaque regression and stabilization
timeFrame: 18 months
Secondary outcomes:
measure: Disease activity and health measures, lipoprotein components and inflammatory biomarkers
timeFrame: 18 months
measure: Carotid artery cholesterol plaque regression and stabilization
timeFrame: 18 months
measure: Carotid artery cholesterol plaque regression and stabilization
timeFrame: 18 months
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Anne Grete Semb, Department of Rheumatology, Diakonhjemmet hospital
Study officials:
affiliation: Diakonhjemmet Hospital
name: Anne G Semb, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Os HA, Rollefstad S, Gerdts E, Kringeland E, Ikdahl E, Semb AG, Midtbo H. Preclinical cardiac organ damage during statin treatment in patients with inflammatory joint diseases: the RORA-AS statin intervention study. Rheumatology (Oxford). 2020 Dec 1;59(12):3700-3708. doi: 10.1093/rheumatology/keaa190.
citation: Svanteson M, Rollefstad S, Klow NE, Hisdal J, Ikdahl E, Semb AG, Haig Y. Associations between coronary and carotid artery atherosclerosis in patients with inflammatory joint diseases. RMD Open. 2017 Sep 17;3(2):e000544. doi: 10.1136/rmdopen-2017-000544. eCollection 2017.
citation: Ikdahl E, Rollefstad S, Hisdal J, Olsen IC, Pedersen TR, Kvien TK, Semb AG. Sustained Improvement of Arterial Stiffness and Blood Pressure after Long-Term Rosuvastatin Treatment in Patients with Inflammatory Joint Diseases: Results from the RORA-AS Study. PLoS One. 2016 Apr 19;11(4):e0153440. doi: 10.1371/journal.pone.0153440. eCollection 2016.
citation: Ikdahl E, Hisdal J, Rollefstad S, Olsen IC, Kvien TK, Pedersen TR, Semb AG. Rosuvastatin improves endothelial function in patients with inflammatory joint diseases, longitudinal associations with atherosclerosis and arteriosclerosis: results from the RORA-AS statin intervention study. Arthritis Res Ther. 2015 Oct 8;17:279. doi: 10.1186/s13075-015-0795-y.
citation: Rollefstad S, Ikdahl E, Hisdal J, Olsen IC, Holme I, Hammer HB, Smerud KT, Kitas GD, Pedersen TR, Kvien TK, Semb AG. Rosuvastatin-Induced Carotid Plaque Regression in Patients With Inflammatory Joint Diseases: The Rosuvastatin in Rheumatoid Arthritis, Ankylosing Spondylitis and Other Inflammatory Joint Diseases Study. Arthritis Rheumatol. 2015 Jul;67(7):1718-28. doi: 10.1002/art.39114.