title: Effect of Randomized Lipid Lowering With Simvastatin and Ezetimibe on Cataract Development (from the Simvastatin and Ezetimibe in Aortic Stenosis Study).
abstract: 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.
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, New York; Department of Cardiology, Roskilde University Hospital, Copenhagen University, Roskilde, Denmark. Electronic address: casperbang@hotmail.com.
authors.forename: Casper N
authors.initials: CN
authors.lastname: Bang
authors.affiliation: Department of Cardiology, Frederiksberg University Hospital, Copenhagen University, Copenagen, Denmark.
authors.forename: Anders M
authors.initials: AM
authors.lastname: Greve
authors.affiliation: Department of Ophthalmology, Glostrup University Hospital, Copenhagen University, Glostrup, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: La Cour
authors.affiliation: Research Unit, Department of Public Health and Clinical Medicine, Umeå University, Skellefteå, Sweden.
authors.forename: Kurt
authors.initials: K
authors.lastname: Boman
authors.affiliation: Department of Cardiology, Heart Center, Freiburg University, Bad Krozingen, Germany.
authors.forename: Christa
authors.initials: C
authors.lastname: Gohlke-Bärwolf
authors.affiliation: Department of Cardiology, University Hospitals of South Manchester, Manchester, United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: Ray
authors.affiliation: Center of Preventive Medicine, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, Oslo, Norway.
authors.forename: Terje
authors.initials: T
authors.lastname: Pedersen
authors.affiliation: Department of Cardiology, Oslo University Hospital, Oslo University, Oslo, Norway.
authors.forename: Anne
authors.initials: A
authors.lastname: Rossebø
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Okin
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Devereux
authors.affiliation: Department of Cardiology, Oslo University Hospital, Oslo University, Oslo, Norway.
authors.forename: Kristian
authors.initials: K
authors.lastname: Wachtell
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D001024:Aortic Valve Stenosis / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D002386:Cataract / Q000453:epidemiology / Q000209:etiology*; D008078:Cholesterol, LDL / Q000097:blood* / Q000187:drug effects; D003718:Denmark / Q000453:epidemiology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000069438:Ezetimibe / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009664:Norway / Q000453:epidemiology; D012307:Risk Factors; D019821:Simvastatin / Q000627:therapeutic use*; D013548:Sweden / Q000453:epidemiology; D006113:United Kingdom / Q000453:epidemiology; D014481:United States / Q000453:epidemiology
chemical_list: D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D019821:Simvastatin; D000069438:Ezetimibe