《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])。
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)。
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。
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.