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他汀类药物与白内障发生率增加相关

Statins linked to higher cataract incidence
来源:爱思唯尔 2013-09-25 09:25点击次数:2025发表评论

《美国医学会杂志-眼科学》9月19日在线发表的一项研究显示,他汀类药物与一个倾向评分匹配队列中白内障发生率增加有关(JAMA Ophthalmol. 2013 Sept. 19 [doi:10.1001/jamaophthalmol.2013.4575])。


Ishak Mansi医生


德克萨斯大学西南医学中心的医学教授Ishak Mansi医生及其同事对德克萨斯州军事医疗保健数据库中所有45,000例成人患者2003年10月1日~2010年3月1日的纵向随访数据进行了分析。研究者采用计算机模式选择可比性非常高的他汀类使用者和非使用者。研究者使用药房记录根据他汀类使用情况对受试者进行分组:13,626例他汀类使用者曾接受至少90天他汀类治疗;32,623例非使用者在研究期间从未接受他汀类治疗。


研究者使用44种预期增加受试者接受他汀类处方可能性和增加白内障风险的变量,进行倾向评分匹配队列分析。这些变量包括年龄、性别、17种合并症、肥胖、酒精依赖/滥用、14组药物的使用,以及其他因素。


在他汀类处方方面,辛伐他汀占处方的73%,阿托伐他汀占17.4%,普伐他汀占7%,瑞舒伐他汀占1.7%,氟伐他汀或洛伐他汀占0.24%。近34%的他汀类使用者接受最大剂量的他汀类治疗。


在初次分析中,研究者匹配了6,972对基线特征无显著差异的他汀类使用者和非使用者。他汀类使用者和非使用者中发生白内障的例数分别为2,477例(35.5%)和2,337例(33.5%),比值比(OR 1.09)具有统计学显著性。


在二次分析中,研究者纳入无预设合并症的6,113例他汀类使用者和27,400例非使用者。他汀类使用者和非使用者的白内障发生率分别为33.7%和9.4%,风险显著增加20%。


进一步分析显示,他汀类的使用是白内障的独立预测因素(校正后OR 1.43),并且使用反向逐步删除法重复分析仍发现他汀类的使用是白内障的独立预测因素(校正后OR 1.42)。


研究者还评估了白内障与LDL胆固醇和HDL胆固醇之间的关联,发现平均LDL胆固醇水平与白内障风险呈负相关(校正后OR 0.997;P=0.009),但平均HDL胆固醇不与白内障风险呈负相关(校正后OR 1.002;P=0.16)。


研究者还根据他汀类使用年数(2、4和6年)对数据进行了分析。不管使用何种方法,结果均一致。研究者表示,该研究存在一些局限性,包括其回顾性观察设计。他们表示,该研究可能还存在其他未被识别的基线混杂因素,并且成功的个体基线特征的倾向评分匹配并不能确保个体差异的综合效应不会影响所研究的终点。此外,虽然大部分他汀类使用者接受他汀类处方的平均累积时间为4.5年,表明具有依从性,但通过药房数据并不能了解他汀类的摄入情况。


Mansi医生表示,这项研究带给医生的最重要信息是,我们目前并未真正了解他汀类药物的所有副作用。医生应根据现行指南来处方他汀类药物,而不应根据推测或轻易开具处方,应考虑具体患者的获益风险比。未来研究应包括常规眼科检查和客观评估工具,而不依赖于患者调查或管理数据。每年与白内障相关的费用支出为50亿美元,随着老年人口日益增加,这一费用可能还会增加。需将认识和优化晶状体混浊的可调控危险因素作为首要的公共卫生议题。


与Mansi 医生的研究不同,新泽西Rutgers Robert Wood Johnson医学院的John B. Kostis 医生日前在欧洲心脏病学会(ESC)年会上公布的对13项研究的荟萃分析显示,他汀类药物对白内障有保护作用,特别是在对年轻人长期处方的情况下。Kostis医生称,已就Mansi医生的研究向JAMA编辑递交了一封信,对研究方法和结果提出了一些问题。


Kim Allan Williams Sr.医生


底特律韦恩州立大学心脏病科主任Kim Allan Williams Sr.医生表示,Mansi 医生的研究完成得非常好,这主要反映在倾向匹配方面。该研究并未对他汀类药物使用与白内障之间的关联给出明确且最终的答案,并且其未否定其他研究观察到的他汀类对白内障的保护作用或得出的两者无关联的结论。Mansi 医生的研究使我们再度陷于需要前瞻性随机对照研究的境地,而要进行前瞻性随机对照研究非常难,因为不能单纯地出于随机化目的而让受试者接受他汀类药物治疗。如果只能进行观察性研究的话,不管观察性研究的规模多大或开展得多好,始终都存在问题。


Mansi医生和Kostis医生声明无经济利益冲突。Williams医生从Astellas Healthcare公司获得顾问费/酬金。


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By: NASEEM S. MILLER, Clinical Endocrinology News Digital Network


Taking statins was associated with a higher incidence of cataract diagnosis in a propensity score–matched cohort and in other analyses of a military health care database in Texas. The report was published online Sept. 19 in JAMA Ophthalmology.


This is yet another observational study to show a possible association between statin use and cataracts – this time a negative one – continuing the ongoing controversy in this area of research.


Investigators said that their propensity score–matched analysis was the first study of its kind, and also one of the largest, including 45,000 patients who were followed up longitudinally within the same health care system, with similar health care coverage and access to care and medication.


The study was extremely well done, Dr. Kim Allan Williams Sr., chair of cardiology at Wayne State University, Detroit, said in an interview. "This is one of the larger studies, and the thing that distinguishes this one is how well the propensity matching was done. Dr. Williams, who was not involved in the study, added that the study wasn’t a definite and final answer to the question, and didn’t negate other studies that showed a protective or no association between statins and cataracts.


Researchers conducted the analysis on all adult patients who were enrolled in the San Antonio Military Multi-Market Area as Tricare Prime or Plus, analyzing the data from October 1, 2003, to March 1, 2010. All patients were enrolled in the system throughout the study.
 
With a computer model, they selected a group of statin users and nonusers who looked very comparable to each other.


"One of the biggest caveats in observational studies is that, patients’ baseline characteristics may be different," Dr. Ishak Mansi, the study’s principal investigator, said in an interview." And when you look after 6 or 7 years, you may have higher incidence of cataract in some, not because of the statins, but because some of the patients who were given statins were sicker from the very beginning. So we have to make sure we’re comparing apples to apples."


They divided the participants according to statin use, using their pharmacy records: There were 13,626 statin users, who had received at least one 90-day supply of a statin; and 32,623 nonusers, who had never received a statin throughout the study.


To conduct a propensity score–matched cohort analysis, researchers used 44 variables that were expected to increase the likelihood of receiving a statin prescription, as well as increasing the risk for cataract. Those variables included age, sex, 17 comorbid conditions, obesity, alcohol dependence/abuse, use of 14 medication groups, and more.


As for statins, simvastatin made up 73% of the prescriptions, atorvastatin 17.4%, pravastatin 7%, rosuvastatin 1.7%, and fluvastatin or lovastatin 0.24% of the prescription. Nearly 34% of the statin users received maximal doses of statins.


For the primary analysis, researchers matched 6,972 pairs of statin users and nonusers, with no significant differences in their baseline characteristics. Among the statin users, cataracts occurred in 2,477 (35.5%), compared with 2,337 (33.5%) of the nonusers, yielding a statistically significant odds ratio of 1.09 (JAMA Ophthalmol. 2013 Sept. 19 [doi:10.1001/jamaophthalmol.2013.4575]).


"Then we said, let us assume that the computer model may not have been good in selecting patients, and let’s see if we can get the same result by slicing the data differently," said Dr. Mansi, professor of medicine at UT Southwestern, Dallas.


The secondary analysis included 6,113 statin users and 27,400 nonusers with no prespecified comorbidities. Among them, 33.7% of statin users and 9.4% of nonusers developed cataracts, a significant 20% increased risk, the researchers reported.


Further analysis showed that statin use was an independent predictor of cataract (adjusted OR, 1.43), and statin use continued to be an independent predictor of cataract, when researchers repeated the analysis using backward stepwise elimination (adjusted OR, 1.42).


They also examined the relationship between cataract and LDL cholesterol and HDL cholesterol, and found that the mean LDL cholesterol level was inversely related to risk for cataract (adjusted OR, 0.997; P = .009), but mean HDL cholesterol was not (adjusted OR, 1.002; P = .16).


They also analyzed the data according to years of statin use (2, 4, and 6 years). "Whatever approach we used, the result was consistent," said Dr. Mansi, a staff internist at VA North Texas, Dallas.


Dr. Williams, vice president of the American College of Cardiology, said that the study puts the issue "into real question again, and we find ourselves wanting a randomized controlled prospective trial, which would be very difficult to do. These are drugs that you just don’t randomize people to. If we’re stuck with observational trials, no matter how large or how well done they are, there will always be questions."


In September, at the annual congress of the European Society of Cardiology, Dr. John B. Kostis of Rutgers Robert Wood Johnson Medical School, New Brunswick, N.J., presented an unpublished meta-analysis of 13 studies, showing that statins had a protective effect on cataracts, especially when they were prescribed to younger people for a longer period of time.


"The bottom line is that statins prevent cataracts," Dr. Kostis said during his presentation at ESC. "But the bottom bottom line is, don’t be scared of cataracts when prescribing statins." (Dr. Kostis said he was submitting a letter to the JAMA editors regarding Dr. Mansi’s study, raising a few questions about the methods and findings.)


Dr. Mansi and colleagues listed several limitations for the study, including its retrospective observational design. They added that there may be other unidentified baseline confounders, and that successful propensity score matching of individual baseline characteristics doesn’t guarantee that the combined effect of individual difference would have no impact on the outcome of interest. Also, using pharmacy data to identify statin use does not capture statin intake, although most users received the prescription for a mean cumulative duration of 4.5 years, which suggests compliance, they noted.


"The most important message for doctors is that we don’t really know yet the full spectrum of side effects of this very effective group of medications," Dr. Mansi said. "They should prescribe this medication in accordance with the current guidelines, not extrapolate, and not prescribe it lightly. Rather, they should consider the benefit-risk ratio for each individual."


Based on the findings, Dr. Williams said, "Look for statin use in diabetes patients, because it can be associated with faster development of cataract. The other thing is, try and make sure within the patients’ care group, whether it’s in a patient-centered home, in primary care, or even in cardiology, that attention is paid to vision and cataract screening, which can become a routine part of physical exam. Unfortunately, that sounds like that we’re convinced by this study. But I think it’s convincing enough to bring our threshold for screening people with cataracts down a little bit."


The authors suggested that future studies should include regular ophthalmologic examinations and objective assessment tools rather than relying on patient surveys or administrative data.


With the growing elderly population, incidence of cataracts, which comes with a whopping cost of $5 billion annually, is likely to increase, and "understanding and optimizing the modifiable risk factors for developing lens opacities must be a public health priority," Dr. Mansi and colleagues wrote.


Dr. Mansi and Dr. Kostis had no disclosures. Dr. Williams has received consultant fees/honoraria from Astellas Healthcare.
 


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学科代码:心血管病学 眼科学   关键词:他汀类药物 白内障
来源: 爱思唯尔
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