Statins for primary prevention of cardiovascular events and mortality in old and very old adults with and without type 2 diabetes: retrospective cohort studyBMJ 2018; 362 doi: https://doi.org/10.1136/bmj.k3359 (Published 05 September 2018) Cite this as: BMJ 2018;362:k3359
- Rafel Ramos, senior researcher1 2 3 4,
- Marc Comas-Cufí, statistician1 2,
- Ruth Martí-Lluch, senior researcher1 2 3,
- Elisabeth Balló, primary care physician1 2 3 4,
- Anna Ponjoan, senior researcher1 2 3,
- Lia Alves-Cabratosa, postdoctoral researcher1 2,
- Jordi Blanch, statistician1 2,
- Jaume Marrugat, senior researcher5 6,
- Roberto Elosua, senior researcher5 6,
- María Grau, senior researcher and associate professor5 6,
- Marc Elosua-Bayes, predoctoral researcher1 2,
- Luis García-Ortiz, senior researcher7,
- Maria Garcia-Gil, senior researcher1 2 4
- 1Institut Universitari d’Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Catalonia, Spain
- 2ISV Research Group. Research Unit in Primary Care, Primary Care Services, Girona. Catalan Institute of Health, Catalonia, Spain
- 3Institut d'Investigació Biomèdica de Girona (IdIBGi), Catalonia, Spain
- 4Department of Medical Sciences, School of Medicine, University of Girona, Spain
- 5Registre Gironí del COR Group (REGICOR); Cardiovascular, Epidemiology and Genetics Research Group (EGEC), Municipal Institute for Medical Research (IMIM), Barcelona, Spain
- 6CIBER of Cardiovascular Diseases, Barcelona, Catalonia, Spain
- 7Institute of Biomedical Research of Salamanca, Primary Care Research Unit, the Alamedilla Health Center, Castilla and León Health Service-SACYL, and Department of Biomedical and Diagnostic Sciences, University of Salamanca, Salamanca, Spain
- Correspondence to: R Ramos, Carrer Maluquer Salvador, 11. 17002 Girona, Spain
- Accepted 17 July 2018
Objective To assess whether statin treatment is associated with a reduction in atherosclerotic cardiovascular disease (CVD) and mortality in old and very old adults with and without diabetes.
Design Retrospective cohort study.
Setting Database of the Catalan primary care system (SIDIAP), Spain, 2006-15.
Participants 46 864 people aged 75 years or more without clinically recognised atherosclerotic CVD. Participants were stratified by presence of type 2 diabetes mellitus and as statin non-users or new users.
Main outcome measures Incidences of atherosclerotic CVD and all cause mortality compared using Cox proportional hazards modelling, adjusted by the propensity score of statin treatment. The relation of age with the effect of statins was assessed using both a categorical approach, stratifying the analysis by old (75-84 years) and very old (≥85 years) age groups, and a continuous analysis, using an additive Cox proportional hazard model.
Results The cohort included 46 864 participants (mean age 77 years; 63% women; median follow-up 5.6 years). In participants without diabetes, the hazard ratios for statin use in 75-84 year olds were 0.94 (95% confidence interval 0.86 to 1.04) for atherosclerotic CVD and 0.98 (0.91 to 1.05) for all cause mortality, and in those aged 85 and older were 0.93 (0.82 to 1.06) and 0.97 (0.90 to 1.05), respectively. In participants with diabetes, the hazard ratio of statin use in 75-84 year olds was 0.76 (0.65 to 0.89) for atherosclerotic CVD and 0.84 (0.75 to 0.94) for all cause mortality, and in those aged 85 and older were 0.82 (0.53 to 1.26) and 1.05 (0.86 to 1.28), respectively. Similarly, effect analysis of age in a continuous scale, using splines, corroborated the lack of beneficial statins effect for atherosclerotic CVD and all cause mortality in participants without diabetes older than 74 years. In participants with diabetes, statins showed a protective effect against atherosclerotic CVD and all cause mortality; this effect was substantially reduced beyond the age of 85 years and disappeared in nonagenarians.
Conclusions In participants older than 74 years without type 2 diabetes, statin treatment was not associated with a reduction in atherosclerotic CVD or in all cause mortality, even when the incidence of atherosclerotic CVD was statistically significantly higher than the risk thresholds proposed for statin use. In the presence of diabetes, statin use was statistically significantly associated with reductions in the incidence of atherosclerotic CVD and in all cause mortality. This effect decreased after age 85 years and disappeared in nonagenarians.
Contributors: RR, MG-G, and MC-C conceived and designed the study. MC-C and JB acquired the data. All authors analysed and interpreted the data. RR and MG-G drafted the manuscript. All authors critically revised the manuscript for important intellectual content. MC-C, JB, and MG-G carried out the statistical analysis. RR and MG-G obtained funding. RM-L, AP, LA-C, JB, and ME-B provided administrative, technical, or material support. RR, MG-G, MC-C, and EB supervised the study. RR and MG-G are guarantors. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.
Funding: This project was supported by clinical research grants from the Ministerio de Salud (EC11-267); Spain’s Ministry of Science and Innovation through the Carlos III Health Institute, co-financed with European Union ERDF funds (Network for Prevention and Health Promotion in primary Care (RedIAPP RD16/0007/0004); the Red de Investigación Cardiovascular (RD12/0042/0061, RD12/0042/0013) and Miguel Servet Contract CP12/03287); and by the Departament de Salut, Generalitat de Catalunya, Agency for Management of University and Research Grants (2014 SGR 240; 2017 SGR 1146). The sponsors had no role in the design and conduct of the study; the collection, management, analysis, or interpretation of the data; or the preparation, review, or approval of the manuscript.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: Ethics approval for observational research using SIDIAPQ data was obtained from the local ethics committee. Informed consent of individual patients was not required as anonymised information was obtained from medical records. In the SIDIAPQ database, confidentiality is rigorously assured by a standardised system of codification that involves all possible identifier variables, which are not available to investigators.
Data sharing: No additional data available.
Transparency: The lead author (RR) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.
This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.