Effects of Rosuvastatin on Carotid Artery Plaques in Patients With Inflammatory Joint Disease

NCT01389388 | Completed

• 2 other identifiers: 2009/22192008-005551-20
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 1

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.

Conditions

Carotid Artery Plaque; Ankylosing Spondylitis; Rheumatoid Arthritis

Keywords

Carotid plaques; inflammatory joint disease; statins; inflammation; lipoprotein components

Outcome Measures

Primary Outcomes (1)

• Carotid artery cholesterol plaque regression and stabilization

  Reduction of plaque area and change of the plaque morphology to less vulnerable for rupture after 18 months with 40 mg Rosuvastatin daily.

  18 months

Secondary Outcomes (3)

• Disease activity and health measures, lipoprotein components and inflammatory biomarkers

  18 months

• Carotid artery cholesterol plaque regression and stabilization

  18 months

• Carotid artery cholesterol plaque regression and stabilization

  18 months

Study Arms (1)

Rosuvastatin intervention

EXPERIMENTAL

Patients \> 70 years will be given Rosuvastatin of 5 mg a day, uptitering the dose until the LDL level of 1.6-1.8 mmol/l has been reached. Patient \<70 years, strat on Rosuvastatin 20 mg a day, uptitered to 40 mg a day, with the LDL of 1.6-1.8 mmol/l. -1.8 mmol/l. The objective is that all the participants should have reached a LDL level of 1.6-1.8 mmol/l 3 months after the start of the study. The participants will remain on Rosuvastatin medication for a total of 18 months.

Drug: Rosuvastatin

Interventions

Rosuvastatin DRUG

All the patients who have signed the informed consent will after they have had performed a MCT and possibly SCC with an IVUS, will be give Rosuvastatinuntill their LDL level has reached 1.6-1.8 mmol/l. The objective is that all the participants should have reached 1.6-1.8 mmol/l 3 months after the start of the study. The participants will remain on Rosuvastatin medication for a total of 18 months.

Also known as: Brand name for Rosuvastatin is Crestor

Rosuvastatin intervention

Eligibility Criteria

• Age: 35 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Concomitant statin treatment
• Arterial fibrillation or others with chronic irregular heart rhythm (because of CT).
• 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
• Secondary hyperlipidemia
• Primary hyperthyroidism

Sponsors & Collaborators

• Diakonhjemmet Hospital: lead

Study Sites (1)

Anne Grete Semb, Department of Rheumatology, Diakonhjemmet hospital

Oslo, Oslo County, NO-0319, Norway

Location

Related Publications (5)

• 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.

  PMID: 32386421 DERIVED

• 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.

  PMID: 28955501 DERIVED

• 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.

  PMID: 27093159 DERIVED

• 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.

  PMID: 26445924 DERIVED

• 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.

  PMID: 25778850 DERIVED

MeSH Terms

Conditions

Carotid Stenosis; Spondylitis, Ankylosing; Arthritis, Rheumatoid; Inflammation

Interventions

Rosuvastatin Calcium

Condition Hierarchy (Ancestors)

Carotid Artery Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Axial Spondyloarthritis; Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Ankylosis; Joint Diseases; Arthritis; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Anne G Semb, MD, PhD

  Diakonhjemmet Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Leader of the Preventive Cardio-Rheuma clinic

Study Record Dates

• First Submitted: April 16, 2010
• First Posted: July 8, 2011
• Study Start: January 1, 2013
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: May 7, 2015

Record last verified: 2015-05

Locations

NO (1)