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Effect of Randomized Lipid Lowering With Simvastatin and Ezetimibe on Cataract Development (from the Simvastatin and Ezetimibe in Aortic Stenosis Study)

Published:October 02, 2015DOI:https://doi.org/10.1016/j.amjcard.2015.09.026
      Recent American College of Cardiology/American Heart Association guidelines on statin initiation on the basis of total atherosclerotic cardiovascular disease risk argue that the preventive effect of statins on cardiovascular events outweigh the side effects, although this is controversial. Studies indicate a possible effect of statin therapy on reducing risk of lens opacities. However, the results are conflicting. The Simvastatin and Ezetimibe in Aortic Stenosis study (NCT00092677) enrolled 1,873 patients with asymptomatic aortic stenosis and no history of diabetes, coronary heart disease, or other serious co-morbidities were randomized (1:1) to double-blind 40 mg simvastatin plus 10 mg ezetimibe versus placebo. The primary end point in this substudy was incident cataract. Univariate and multivariate Cox models were used to analyze: (1) if the active treatment reduced the risk of the primary end point and (2) if time-varying low-density lipoproteins (LDL) cholesterol lowering (annually assessed) was associated with less incident cataract per se. During an average follow-up of 4.3 years, 65 patients (3.5%) developed cataract. Mean age at baseline was 68 years and 39% were women. In Cox multivariate analysis adjusted for age, gender, prednisolone treatment, smoking, baseline LDL cholesterol and high sensitivity C-reactive protein; simvastatin plus ezetimibe versus placebo was associated with 44% lower risk of cataract development (hazard ratio 0.56, 95% confidence interval 0.33 to 0.96, p = 0.034). In a parallel analysis substituting time-varying LDL-cholesterol with randomized treatment, lower intreatment LDL-cholesterol was in itself associated with lower risk of incident cataract (hazard ratio 0.78 per 1 mmol/ml lower total cholesterol, 95% confidence interval 0.64 to 0.93, p = 0.008). In conclusion, randomized treatment with simvastatin plus ezetimibe was associated with a 44% lower risk of incident cataract development. This effect should perhaps be considered in the risk-benefit ratio of statin treatment.
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      Linked Article

      • Prevention of Cataract by Statins
        American Journal of CardiologyVol. 117Issue 7
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          Bang et al1 report that randomized treatment with simvastatin plus ezetimibe was associated with a 44% lower incidence of cataracts in the Simvastatin and Ezetimibe in Aortic Stenosis Study (SEAS) trial. Meta-analysis including the SEAS trial and previous studies indicates that the statin use is associated with a clinically and statistically significant decrease in the occurrence of cataracts. The findings of SEAS confirm the results of our previous meta-analysis,2 where a significant protective effect of statins was observed in 8 observational studies (odds ratio [OR] 0.81, 95% CI 0.70 to 0.93, p = 0.004), whereas an effect of similar magnitude was observed in the 6 randomized trials but did not reach statistical significance (OR 0.84, 95% CI 0.67 to 1.05, p = 0.119).
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          We read the recently published study entitled “Effect of randomized lipid lowering with simvastatin and ezetimibe on Cataract Development”.1 The investigators report a 44% lower risk of incident cataract development in the treatment arm of the study. The role of statins in the development of cataracts has been debated for years with studies reporting a deleterious, neutral, or protective effect.2,3
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