Epidemiological studies have identified several risk factors for CVD. These include both non-modifiable factors such as age, family history, and male sex; and modifiable factors, such as smoking, blood pressure, and cholesterol levels. The identification and management of these modifiable risk factors is an important step for reducing the risk of CVD and cardiovascular events in patients at any age.
Treatment with more intensive statin doses has been shown to have significantly greater effects than moderate statin therapy on cholesterol reduction in the general population; and the use of intensive lipid-altering therapy is supported in older subjects as well[5, 6]. A recent observational study of clinical practice in Europe and Canada highlights the need for better management of dyslipidemia, with almost half of the 22,063 statin-treated patients studied (mean age of 65.7 ± 9.9 years) having LDL-C levels above guideline recommended targets.
The present post hoc analysis showed that in subjects aged 65 years and older, the odds of achieving the LDL-C, non-HDL-C and Apo B treatment targets recommended by the 2012 Canadian and 2012 European treatment guidelines were greater with the combination of atorvastatin 10 mg plus ezetimibe 10 mg compared with uptitration of atorvastatin to 20 mg for 6 weeks and 40 mg for an additional 6 weeks. Moreover, in the subgroup of subjects at very high risk, the odds of achieving the most aggressive lipid targets were greater with the combination compared with uptitration at both 6 weeks and 12 weeks, similar to the odds of target achievement in the overall population. In the subgroup of subjects at high risk; however, the odds of achieving most of the recommended targets were similar for both treatments at both 6 weeks and 12 weeks. These results were consistent with the primary analysis which evaluated the attainment of LDL-C <70 mg/dL or LDL-C <100 or <70 mg/dL for all subjects.
It has been suggested that statin therapy should be used more conservatively in older patients, especially in those with an increased susceptibility to adverse events due to concomitant illnesses and/or medications. Although the Study Assessing Goals in the Elderly (SAGE) demonstrated greater benefits of intensive versus moderate statin therapy, suggesting that the benefits may outweigh the concerns, caution is advised when prescribing statins in individuals older than 65 years due to increased risk of myopathy. The United States Food and Drug Administration has restricted the use of the 80 mg dose of simvastatin in populations at any age[15–17]. Combination therapy with drugs that have different mechanisms of action may be beneficial for lipid-lowering in older patients. A pooled analysis that included 16 studies showed that ezetimibe used in combination with a statin lowered LDL-C 17% more than statin monotherapy at equivalent doses in those aged under 65, 65-74 and 75 years and older. In addition, the proportion of subjects achieving LDL-C <100 mg/dL or <70 mg/dL was greater with the combination therapy versus statin monotherapy in all age groups. The current analyses are consistent with these previous reports, suggesting that therapy with ezetimibe added to moderate doses of atorvastatin may provide a valuable lipid-lowering option for older men and women at high and very high risk for CVD. Of note, whether LDL-C reductions attributed to combination treatment versus statin monotherapy will result in better CVD outcomes is not yet known and awaits results from an ongoing clinical trial.
Compared with the overall population and the very high risk subgroup, which had similar group sizes to each other, the high risk subgroup in this analysis was relatively small and underpowered to show statistical significance based on associated 95% confidence intervals. While odds ratios for the high risk subjects were generally consistent with the odds ratios for the overall population, limited sample size prohibits making definitive statements concerning the significance of these differences. The results of these analyses were based on a study of relatively short duration in a population that was predominantly white (96%), which limits the ability to generalize the conclusions to longer-term therapy and diverse populations. Of note, the guidelines also include a 50% LDL-C reduction; but we could not assess this as we did not have baseline naïve LDL-C levels. Finally, these were post hoc analyses; no inferential statistics were provided and no adjustments for multiplicity were made. Therefore, although the results provide information about the efficacy of ezetimibe combined with atorvastatin in older subjects, they should be interpreted with discretion.