title: Incidence of cancer and mortality in patients from the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial.
abstract: The Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) clinical trial, including 1,873 patients found an increased risk for cancer with lipid-lowering therapy with ezetimibe/simvastatin 10/40 mg/day, relative to placebo. In a registry-based follow-up study over 21 months from the conclusion of the SEAS trial, new incident cancer and total mortality were investigated in the SEAS study cohort from Denmark, Finland, Norway, Sweden, and the United Kingdom. Among 1,359 subjects eligible for follow-up (73% of the original total cohort), 1,194 had no history of cancer (primary follow-up cohort). New cancers and deaths were identified in the national cancer and mortality registries and classified by an Expert Review Committee. Data were analyzed using Cox proportional-hazards models of new cancers and mortality during follow-up according to treatment group assigned in the SEAS base study and with age, gender, smoking history, and previous cancers as covariates. The primary follow-up cohort had 12 patients with new cancers in the ezetimibe/simvastatin group and 22 in the placebo group (hazard ratio 0.55, 95% confidence interval 0.27 to 1.11), indicating no significant difference between the treatment groups. During follow-up, 43 patients assigned to ezetimibe/simvastatin and 33 assigned to placebo died (hazard ratio 1.29, 95% confidence interval 0.82 to 2.03). In conclusion, in this registry-based observational follow-up study of the original SEAS study patient population, treatment with ezetimibe/simvastatin was not associated with an increased risk for cancer or mortality in the 21-month period after the completion of the original SEAS study.
authors.affiliation: Institute of Applied Economics and Health Research, Copenhagen, Denmark; Odense Patient Data Explorative Network, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark. Electronic address: agreen@health.sdu.dk.
authors.forename: Anders
authors.initials: A
authors.lastname: Green
authors.affiliation: Merck & Company, Inc., Whitehouse Station, New Jersey.
authors.forename: Dena Rosen
authors.initials: DR
authors.lastname: Ramey
authors.affiliation: Institute of Applied Economics and Health Research, Copenhagen, Denmark.
authors.forename: Martha
authors.initials: M
authors.lastname: Emneus
authors.affiliation: Institute of Applied Economics and Health Research, Copenhagen, Denmark.
authors.forename: Maria
authors.initials: M
authors.lastname: Iachina
authors.affiliation: Institute of Clinical Medicine Akershus University Hospital, University of Oslo, Oslo, Norway; Department of Pulmonary Medicine, Medical Division, Akershus University Hospital, Oslo, Norway; Health Services Research Unit, Akershus University Hospital, Lørenskog, Norway.
authors.forename: Knut
authors.initials: K
authors.lastname: Stavem
authors.affiliation: Centre for Health Economics and the Department of Economics and Statistics, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Kristian
authors.initials: K
authors.lastname: Bolin
authors.affiliation: Institute of Health and Society, Newcastle University, Sir James Spence Institute, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: McNally
authors.affiliation: Merck & Company, Inc., Whitehouse Station, New Jersey.
authors.forename: Michael
authors.initials: M
authors.lastname: Busch-Sørensen
authors.affiliation: Department of Cardiology, Lund University, University Hospital, Malmö, Sweden.
authors.forename: Ronnie
authors.initials: R
authors.lastname: Willenheimer
authors.affiliation: Medical Division, Odense University Hospital Svendborg Hospital, Svendborg, Denmark.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Egstrup
authors.affiliation: Institute of Clinical Medicine, Department of Medicine, University of Oulu and Medical Research Center, Oulu University Hospital, Oulu, Finland.
authors.forename: Y Antero
authors.initials: YA
authors.lastname: Kesäniemi
authors.affiliation: Department of Cardiology, Northwest Heart Centre, University Hospitals of South Manchester, Manchester, United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: Ray
authors.affiliation: Institute of Health and Society, Newcastle University, Sir James Spence Institute, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom.
authors.forename: Nermine
authors.initials: N
authors.lastname: Basta
authors.affiliation: Merck & Company, Inc., Whitehouse Station, New Jersey.
authors.forename: Christi
authors.initials: C
authors.lastname: Kent
authors.affiliation: Center of Preventive Medicine, Oslo University Hospital Ullevål, and Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Terje R
authors.initials: TR
authors.lastname: Pedersen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001024:Aortic Valve Stenosis / Q000188:drug therapy; D001384:Azetidines / Q000009:adverse effects / Q000627:therapeutic use; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005060:Europe / Q000453:epidemiology; D000069438:Ezetimibe; D005500:Follow-Up Studies; D015994:Incidence; D009369:Neoplasms / Q000453:epidemiology / Q000209:etiology; D012042:Registries; D012189:Retrospective Studies; D018570:Risk Assessment / Q000379:methods; D019821:Simvastatin / Q000009:adverse effects / Q000627:therapeutic use; D015996:Survival Rate / Q000639:trends; D013997:Time Factors
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D000069438:Ezetimibe; D019821:Simvastatin