Good adherence to therapy with statins reduces the risk of adverse clinical outcomes even among very elderly. Evidence from an Italian real-life investigation

BACKGROUND. Statins, are to date the most effective drugs for the treatment of hypercholesterolemia, and their important protective role in the prevention of cardiovascular (CV) morbidity and mortality is well-established [1]. Since people aged between 60 and 79 years were well represented in many trials, this applies also to elderly patients [2]. However, it does not apply to patients aged 80 years or older, because (i) none or few octogenarians have been included in outcome-based trials and (ii) evidence on the protective effects of statins among them is limited to only few observational studies with inconsistent results [3,4]. This represents an important limitation because the increasing life expectancy makes octogenarians the fastest growing subgroup of the population and, furthermore, this highly advanced aged subgroup accounts for a considerable portion of the overall CV events, hospitalizations and deaths [5]. AIM. To assess whether in individuals aged 80 years or older adherence to statins is accompanied by a reduced risk of all-cause mortality and major cardiovascular events. METHODS. A nested case–control study was carried out including a cohort of patients aged 80 years or older, who were under treatment with statins between 2008 and 2009, using the administrative databases of Lombardy region (Italy). Cases were the cohort members who experienced death or hospitalization for stroke, myocardial infarction or heart failure from the initial prescription until 2012. Up to five controls were randomly selected for each case. Logistic regression was fitted to estimate the odds ratio (OR), and its 95% confidence interval (CI), for the considered outcomes in relation to the adherence to therapy with statins, measured by the proportion of days covered (PDC). Four categories of adherence were employed (i.e., <25%, 25-49%, 50-74%, >=75%), using the lowest one (<25%) as reference. Two younger patient cohorts aged 60 to 69 years and 70 to 79 years were taken for comparison. A Monte-Carlo Sensitivity Analysis was performed to address the potential bias generated by unmeasured confounders (e.g. depression). RESULTS. Among the 571’203 statin users, 273’769 met the inclusion criteria and were enrolled in the study. Compared with younger individuals, very elderly cohort members (80 years or older; mean age 83 years) more often started therapy with low potency statins, exhibited co-treatments and comorbidities, including previous CV events, and had a lower adherence to statins during follow-up. In the octogenarian group, as Figure 1 shows, the risk of all-cause death decreased progressively and steeply as adherence to statins increased, with no noticeable difference from what observed in the two younger age strata. Figure 2 shows that this was also the case for all CV and cause-specific outcomes, although in all age strata the trend was clearer for heart failure than for myocardial infarction and stroke. Indeed, among very elderly individuals, increasing adherence to statin from <25% to ≥75% showed significant risk reductions of death (56%; 95% CI, 53% to 58%), myocardial infarction (15%; 5% to 24%), stroke (13%; 0% to 24%) and heart failure (29%; 23% to 35%). Adherence-related risk reductions were only slightly better for younger cohort members. The data provided by the main analysis were confirmed by the sensitivity analysis. CONCLUSION. In patients aged 80 years or older adherence to statins markedly reduced the risk of fatal and non-fatal CV outcomes, similarly to what occurred in less old patients. Adherence to treatment was also accompanied by a reduction of all-cause death, indicating a favourable effect on residual life expectancy