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.