A Multicenter, Randomized, Placebo-Controlled Trial of Atorvastatin for the Primary Prevention of Cardiovascular Events in Patients With Rheumatoid Arthritis复制标题

阿托伐他汀用于类风湿关节炎患者心血管事件一级预防的多中心、随机、安慰剂对照试验

Despite major advances in therapy over the last two decades, rheumatoid arthritis (RA) continues to be associate d with reduced life expectancy compared to the general population. Almost half of all deaths in RA (about 35-40% of the excess deaths) are attributed to cardiovascular disease (CVD). There are many mechanisms that may underlie Accepted Article This article is protected by copyright. All rights reserved. the increased CVD morbidity and mortality in RA but their crosstalk and relative contribution s are not yet fully elucidated. CVD risk factors including smoking, hypertension, dyslipidemia, increased adiposity, and reduced physical activity are highly prevalent in RA but do not account fully for the excess CVD. A significant part is attributed to “novel” CVD risk factors, such as ‘high -grade’ inflammation promoting atherothrombotic cardiovascular events (CVE). Risk algorithms developed for the general population may underestimate CV E risk in patients with RA, even when multipliers are applied, as in recently updated European recommendations. This makes identification of RA patients who would benefit from primary prevention therapy less precise, leads to significant underuse of statins even in patients who fulfil general population thresholds for statin treatment and has led some to suggest universal prescription of statins in RA, as practiced in diabetes mellitus (DM). The efficacy of statins in the primary and secondary prevention of CVE has been demonstrated in large -scale trials and meta -analyses. CVE reduction is related to the degree of low density lipoprotein cholesterol (LDLc) reduction. Each mmol/L reduction in LDLc is associated with a 20-22% lowering of the risk of myocardial infarction (MI), revasculari zation and stroke. In RA, high -grade inflammation is associate d with a suppression of total cholesterol (TC), LDL c and high density lipoprotein cholesterol (HDLc) levels, as well as changes in lipid structure and function promoting atherosclerosis. The potential pleiotropic anti-inflammatory/immunomodulatory effect s of statins may therefore be more relevant in RA than in the general population. In the TARA trial, atorvastatin 40mg daily, as an adjunct to disease modifying anti-rheumatic drug (DMARD) therapy, provided a modest additional benefit for inflammatory control of RA, at least in a subgroup of patients, while the Tayside controlled study of rosuvastatin in RA suggested a potentially Accepted Article This article is protected by copyright. All rights reserved. beneficial effect on C-reactive protein (CRP) levels. The extent to which statins affect lipid levels and reduce CVE in RA remain s uncertain, due to the small number of RA patients included in general population trials.

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