Statins for Primary Prevention of Cardiovascular Events and Mortality in the Elderly
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This retrospective cohort study used data from 46,864 individuals to examine the effects of statin treatment on atherosclerotic cardiovascular disease (CVD) and mortality in an elderly population. All participants were at least 75 years of age and did not have clinically recognized CVD at baseline. There was a significant association between the use of statins and lower all-cause mortality and atherosclerotic CVD in patients with type 2 diabetes, but this decreased with age and was not present in nonagenarians. In patients without type 2 diabetes, there was no association between statin treatment and reductions in either all-cause mortality or atherosclerotic CVD.
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The authors note that these findings may not be sufficient to make clinical recommendations but that they suggest a need for randomized clinical trials and that statins may not be useful for primary prevention in older patients without type 2 diabetes.
abstract
This abstract is available on the publisher's site.
Access this abstract nowOBJECTIVE
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.
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Additional Info
Statins for Primary Prevention of Cardiovascular Events and Mortality in Old and Very Old Adults With and Without Type 2 Diabetes: Retrospective Cohort Study
BMJ 2018 Sep 05;362(xx)k3359, R Ramos, M Comas-Cufí, R Martí-Lluch, E Balló, A Ponjoan, L Alves-Cabratosa, J Blanch, J Marrugat, R Elosua, M Grau, M Elosua-Bayes, L García-Ortiz, M Garcia-GilFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Ramos et al now present a retrospective primary prevention cohort analysis of the elderly (age 75–90+ years old; mean age, 77 years; median follow-up, 5.6 years) from a large database (N=46,864, of which 17% had diabetes). The key finding was that, after multi-logistic analyses, those without diabetes had no significant benefits for CV events or all-cause mortality, whereas those with diabetes aged 75 to 84 years had a significant 20% to 25% reduction in CV outcomes, including stroke, and a 12% reduction in all-cause mortality; these benefits attenuated after age 84 years.
No appreciable safety concerns were observed, although most of the participants used low- to medium-potency statins. Also, the number of individuals with diabetes initiating statins was small (n=132). Despite the limitations of retrospective analyses, these findings support the use of statin therapy in primary prevention of patients with diabetes, a high-risk category with increasing longevity.
According to NHANES data, all individuals aged ≥75 years are candidates for statin therapy by the current ACC/AHA cholesterol guidelines. We can anticipate a greater clarity in the risk/benefit relationship for statin therapy from an ongoing, primary prevention RCT, STAtin therapy for Reducing Events in the Elderly (STAREE; NCT02099123), with atorvastatin 40 mg vs placebo in 18,000 “healthy” people aged ≥70 years. This trial is scheduled for completion in 2022.
The AHA/ACC ASCVD risk model is heavily weighted on age. For example, if you include a 75-year-old female with a total cholesterol of 200, HDL of 50, and a normal BP (120/80), her 10-year risk is 14.3%. The calculator suggests that she should be on a moderate- to high-intensity statin. Likewise, a 70-year-old male with the same numbers would have a 10-year risk of 16.3% and treatment options are the same. A very timely paper by Ramos et al demonstrates that statin treatment in the nondiabetic elderly is without benefit. It appears that the AHA/ACC ASCVD risk calculator may not be accurate in the elderly.
Most primary care providers would agree that having diabetes for 5 years increases CV risk fivefold. Diabetes is now considered by most physicians as equivalent to a patient having CVD (MI, CVA, PAD). As a primary care provider, I routinely treat elderly patients with diabetes and start both metformin and high-dose statin therapy. Likewise, in the elderly nondiabetic patient, I had been offering a moderate-dose statin based on the ASCVD calculator. Based on these new data, treating the nondiabetic elderly without CVD should not include statin therapy. Many patients are on medications that may, or may not, be indicated. If you care for elderly nondiabetic patients without evidence of CVD, then statin therapy should be stopped.
In the elderly, primary care providers economize on the number of medications to reduce side effects including metabolic complications, ER visits, and even death. Some 15 years ago, a patient was admitted for rule-out CAD, which was ruled out, but she went home on high-dose atorvastatin only to return to the hospital with rhabdomyolysis. Unfortunately, in my 30 years at this medical center, she was the only mortality associated with statin-induced rhabdomyolysis. Clinical indications should be used for statin therapy, and when statin therapy is not indicated, it should be stopped. The risk calculator has age as a highly weighted factor and may need to be adjusted based on this new data. It may be time to withdraw statin therapy for those healthy nondiabetic elderly who have been lucky to make it to their seventh, eighth, and ninth decade of life.