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| ID | Type | Description | Link |
|---|---|---|---|
| 2008-005551-20 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Disease activity and health measures, lipoprotein components and inflammatory biomarkers | Disease activity and Health status i. Disease activity will be measured by: 28-swollen-joint count, AIMS2, BASDAI ii. Health status will be measured by MHAQ, BASFI, Pain VAS, Fatigue VAS, life quality (HRQoL) | 18 months |
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Inclusion Criteria:
Exclusion Criteria:
Concomitant statin treatment
Arterial fibrillation or others with chronic irregular heart rhythm (because of CT).
Contraindication to statin treatment.
Secondary hyperlipidemia
Other diseases or treatment that reduces the safety, or treatment with Rosuvastatin which would interfere with the end points of the study
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| Name | Affiliation | Role |
|---|---|---|
| Anne G Semb, MD, PhD | Diakonhjemmet Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Anne Grete Semb, Department of Rheumatology, Diakonhjemmet hospital | Oslo | Oslo | NO-0319 | Norway |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32386421 | Derived | 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. | |
| 28955501 | Derived |
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| ID | Term |
|---|---|
| D016893 | Carotid Stenosis |
| D013167 | Spondylitis, Ankylosing |
| D001172 | Arthritis, Rheumatoid |
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D002340 | Carotid Artery Diseases |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| D000068718 | Rosuvastatin Calcium |
| ID | Term |
|---|---|
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D005464 | Fluorobenzenes |
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|
|
| Carotid artery cholesterol plaque regression and stabilization |
Lipoprotein components: Lipids, apolipoproteins, magnitude and functional measurements of these, for example of HDL |
| 18 months |
| Carotid artery cholesterol plaque regression and stabilization | Biomarkers/inflammation parameters | 18 months |
| 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. |
| 27093159 | 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. |
| 26445924 | 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. |
| 25778850 | 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. |
| D009422 | Nervous System Diseases |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D000089183 | Axial Spondyloarthritis |
| D025242 | Spondylarthropathies |
| D025241 | Spondylarthritis |
| D013166 | Spondylitis |
| D013122 | Spinal Diseases |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D000844 | Ankylosis |
| D007592 | Joint Diseases |
| D001168 | Arthritis |
| D012216 | Rheumatic Diseases |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006845 |
| Hydrocarbons, Fluorinated |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |