Primary prevention with statins only in elderly T2DM patients aged <85 years
Statins for primary prevention of cardiovascular events and mortality in old and very old adults with and without type 2 diabetes: retrospective cohort studyLiterature - Ramos R, Comas-Cufí M,Martí-Lluch R et al. - BMJ 2018;362:k3359
Introduction and methods
CVD incidence and mortality rates are almost three times higher in individuals ≥75 years, compared to younger people . Current guidelines on CV prevention recommend statin treatment in almost all patients aged ≥75 years, based on 10-years risk estimation, as CVD incidence is highly dependent on age [2-5]. However, recent reports showed no benefit of pravastatin in primary prevention in adults aged ≥75 years . Moreover, the benefit of statins in primary prevention of CVD in older people with type 2 diabetes (T2DM) has not been sufficiently evaluated . Therefore, this study aimed to assess whether use of statins was associated with reduced incidence of atherosclerotic CVD (ASCVD) and mortality in older individuals without CVD, by T2DM and age.
This retrospective cohort study (2006-2015) using data from Spanish Information System for the Development of Research in Primary Care (SIDIAP) included all individuals aged ≥75 years without a history of CVD, who had at least one visit recorded in the electronic medical records during the 1.5 years before the index date (n=46,864). Eligible subjects were followed for a median of 7.7 years. Exposure of patients to statins was stratified according to cholesterol reduction capacity of these drugs: low (≤30%), moderate (31-40%), high (41-50%), and very high (>50%). Liver toxicity and myopathy that occurred within 12 months of treatment initiation and new diagnosis of T2DM, cancer and hemorrhagic stroke after one year were considered as adverse effects of statin use.
Primary outcomes were total mortality and ASCVD, a composite of CHD (fatal and on-fatal angina, fatal and non-fatal myocardial infarction or cardiac revascularization), and stroke (fatal and non-fatal ischemic stroke). Secondary outcomes were CHD and ischemic stroke.
- In patients without T2DM aged 75-84 years, the hazard ratios for statin use were 0.94 (95%CI: 0.86-1.04) for ASCVD and 0.98 (95%CI: 0.91-1.05) for all-cause mortality.
- Similar results were observed in patients without T2DM aged ≥85 years: HR: 0.93 (95%CI: 0.82-1.06) and HR:0.97 (95%CI: 0.90-1.05), respectively.
- In T2DM patients aged 75-84 years, the hazard ratios for statin use were 0.76 (95%CI: 0.65-0.89) for ASCVD and 0.84 (95%CI: 0.75-0.94) for all-cause mortality; one-year NNT was 164 for ASCVD and 306 for all-cause mortality.
- In T2DM patients aged ≥85 years, the hazard ratios for ASCVD and all-cause mortality were HR: 0.82 (95%CI: 0.53-1.26) and HR: 1.05 (95%CI: 0.86-1.28), respectively.
- In the estimation for hazard ratios for each year of age, the hazard ratios showed a statistically significant and clinically relevant reduction in ASCVD in T2DM patients treated with statins. This reduction lost statistical significance at age 85 years. Reduction in all-cause mortality lost statistical significance at age 82 years or more. The reduction in incidence of ASCVD and in all-cause mortality disappeared in nonagenarians.
- No significant increase in adverse events due to statins was observed.
The effect of statin therapy in primary prevention in older subjects varied depending on the presence of T2DM. There was no association between statins and reduction in ASCVD or all-cause mortality in participants aged ≥75 years without CVD and T2DM. In contrast, statins were significantly related to a reduction in the incidence of ASCVD and in all-cause mortality in T2DM participants. This effect was substantially reduced after the age of 85 years and disappeared in nonagenarians. Altogether, these results suggest statin treatment in patients with T2DM aged <85 years.
In their editorial comment , Ryan et al. discuss limitations of the study by Ramos et al., including a small number of patients taking high intensity statins, which may underestimate the risk of myopathy, and the lack of information about adverse effects on cognition. They emphasize that the limited protective effects of statins found in this study should be further studied in randomized trials and the effect of statins on CVD death, which was not recorded in this study, should be further investigated as well. The authors conclude: ‘A patient preference for reduction in myocardial infarction or stroke, however, might help to tilt the balance in favor of statin prescription, but the absolute risk reduction and number needed to treat to prevent a CVD event in older patients remains uncertain.’