Centre for Health Protection, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
Department of Toxicogenomics, Maastricht University Medical Center, Maastricht, The Netherlands.
PLoS One. 2018 Feb 23;13(2):e0193297. doi: 10.1371/journal.pone.0193297. eCollection 2018.
We examined the association between statin use and the risk of rheumatoid arthritis (RA), with special focus on describing the patterns of risks of RA during statin exposure in a large population-based cohort in the United Kingdom. In the Clinical Practice Research Datalink, patients aged ≥40 years with at least one prescription of statins (1995-2009) were selected, and matched by age (+/-5 years), sex, practice and date of first prescription of statins to non-users. The follow-up period of statin use was divided into periods of current, recent and past exposure, with patients moving between these three exposure categories over time. Time-dependent Cox models were used to derive hazard ratios (HRs) of RA, adjusted for disease history and previous drug use. The study population included 1,023,240 patients, of whom 511,620 were statin users. No associations were found between RA and current (HRadj,1.06;99%CI:0.88-1.27) or past statin users (HRadj,1.18;99%CI:0.88-1.57). However, in patients who currently used statins, hazard rates were increased shortly after the first prescription of statins and then gradually decreased to baseline level. The risk of developing RA was increased in recent statin users, as compared to non-users (HRadj,1.39;99%CI:1.01-1.90). The risk of RA is substantially increased in the first year after the start of statins and then diminishes to baseline level. These findings may suggest that statins might accelerate disease onset in patients susceptible to develop RA, but in other patients, statins are probably safe and well tolerated, even after prolonged use. Alternatively, we cannot rule out that confounding by cardiovascular risk factors and ascertainment bias may have influenced the findings.
我们研究了他汀类药物的使用与类风湿关节炎(RA)风险之间的关系,特别关注在英国一个大型基于人群的队列中描述他汀类药物暴露期间 RA 风险的模式。在临床实践研究数据链接中,选择了年龄≥40 岁且至少有一次他汀类药物处方(1995-2009 年)的患者,并通过年龄(+/-5 岁)、性别、实践和他汀类药物首次处方日期与非使用者匹配。他汀类药物使用的随访期分为当前、近期和过去暴露期,患者随着时间的推移在这三个暴露类别之间移动。使用时间依赖性 Cox 模型得出 RA 的风险比(HR),调整了疾病史和先前的药物使用情况。研究人群包括 1,023,240 名患者,其中 511,620 名患者为他汀类药物使用者。RA 与当前(HRadj,1.06;99%CI:0.88-1.27)或过去使用他汀类药物(HRadj,1.18;99%CI:0.88-1.57)的患者之间无关联。然而,在当前使用他汀类药物的患者中,在首次开处方后不久,危险率增加,然后逐渐降至基线水平。与非使用者相比,近期使用他汀类药物的患者发生 RA 的风险增加(HRadj,1.39;99%CI:1.01-1.90)。RA 的风险在开始使用他汀类药物后的第一年显著增加,然后降至基线水平。这些发现可能表明他汀类药物可能会加速易患 RA 的患者的疾病发作,但在其他患者中,即使长期使用,他汀类药物也是安全且耐受良好的。或者,我们不能排除心血管危险因素和确定偏倚可能会影响研究结果。