Reanalysis of two studies with contrasting results on the association between statin use and fracture risk: the General Practice Research Database

被引:51
作者
de Vries, Frank
de Vries, Corinne
Cooper, Cyrus
Leufkens, Bert
van Staa, Tjeerd-Pieter
机构
[1] Univ Utrecht, Inst Pharmaceut Sci, Div Pharmacoepidemiol & Pharmacotherpy, Utrecht, Netherlands
[2] Univ Surrey, Postgrad Med Sch, Dept Pharmacoepidemiol, Guildford GU2 5XH, Surrey, England
[3] Univ Southampton, Southampton Gen Hosp, MRC, Environm Epidemiol Unit, Southampton, Hants, England
基金
英国医学研究理事会;
关键词
hydroxymethylglutaryl-CoA reductase inhibitors; bone fractures; epidemiological bias; case-control studies; selection bias; healthy worker effect;
D O I
10.1093/ije/dyl147
中图分类号
R1 [预防医学、卫生学];
学科分类号
1004 ; 120402 ;
摘要
Background Two recent case-control studies by Meier et al. and van Staa et al. used the UK General Practice Research Database (GPRD) to examine the association between the use of statins and the risk of fractures, with different results. The objective of the present study was to examine methodological explanations for the discrepant results. Methods We created two datasets, which mimicked the previous study designs: a 'selected population' (SP) case-control dataset, with fracture cases matched to controls nested within a selected cohort (Meier et al.), and an 'entire population' (EP) case-control dataset, with both cases and controls sampled from the total GPRD population (van Staa et al.). Cases and controls were matched by gender, age (year of birth or 5 year age bands), and general practice. Results The study included 131 855 fracture cases. The crude odds ratio (OR) for hip fracture in statin users was 0.37 (95% CI 0.27-0.52) in the SP and 0.54 (95% CI 0.39-0.74) in the EP dataset. This difference was reduced when matching by year of birth, rather than by 5 year age bands: crude ORs were 0.58 (95% CI 0.43-0.79) and 0.61 (95% CI 0.44-0.88), respectively. In the SP dataset, 37% of the cases could be matched by year of birth, while this was achieved for 99% in the 'EP' dataset. The exposure time-window, the selection of confounders, and exclusion of high-risk patients also influenced results. Conclusion Residual confounding by a matching variable and different definitions of the exposure time window explained differences in results. In case-control studies of drug use and fracture risk, broad matching criteria for age should be avoided and the selection of the time-window for exposure should be carefully considered.
引用
收藏
页码:1301 / 1308
页数:8
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