Statins for Primary Prevention of Cardiovascular Events and Mortality in Older Adults

Kristen Schroeder, Pharm.D., St. Cloud VA

Background: The efficacy of statins for secondary prevention of cardiovascular events in older patients is well established. However, less is known regarding the benefits of statins in older adults with no history of atherosclerotic cardiovascular disease (ASCVD). This uncertainty also holds true for those with type 2 diabetes, a notable risk factor for ASCVD. Age itself is a risk factor for ASCVD, and it is estimated that ASCVD incidence and mortality rates are almost three times higher in those over age 74 years than in younger adults. As both the population’s longevity and statin prescriptions in older adults are increasing, it is imperative to determine whether statins benefit older adult patients with or without type 2 diabetes.

Objective: To determine whether statin use is linked to incidence of ASCVD and all-cause mortality in older adults (defined as 75 years and older) with or without type 2 diabetes.

Study Design: Authors utilized the Spanish Information System for Development of Research in Primary Care (SIDIAP) database to conduct this retrospective cohort study. Subjects included all registered persons age 75 years and older between July 2006 and December 2007. Notable exclusion criteria included ASCVD history, medications for cardiac diseases, type 1 diabetes, and prior lipid lowering treatment. “Statin non-users” were compared to “statin new users” (defined as having initiated a statin in the previous 18 months), and data was stratified according to the presence of type 2 diabetes.  Information collected included age, sex, blood pressure, body mass index, vascular risk factors, comorbidities, lipid panel, cholesterol reduction capacity of statin (if applicable), and other medications. Of note, statin adherence rate was not assessed. Multiple imputations were performed for any missing data. Primary outcomes were all-cause mortality and ASCVD, defined as a composite of coronary heart disease and stroke. A simulated intention-to-treat method was used, which prevented a subject from switching study groups despite any changes in statin treatment. A parallel statistical analysis was performed by stratifying subjects by the following age groups: old (75-84 years) and very old (≥85 years).

Results: The study population included 46,864 persons, including 7,502 (16%) “statin new users.” Among all subjects, 7,880 (17%) had type 2 diabetes. The majority (>70%) of statin new users took statins considered to have “moderate” cholesterol lowering capacity (defined as a 31-40% reduction). Of note, numerical baseline rates of hypertension, hypercholesterolemia, obesity, tobacco use, and concurrent medication use (including aspirin and beta blockers) were greater in the diabetes group; however, this did not translate to any statistically significant baseline differences between groups. Median follow-up was 5.6 years. In the non-diabetes group, there was no significant difference in ASCVD or all-cause mortality between statin non-users and statin new users in either age group. In the diabetes group, there was a 24% reduction in ASCVD (HR 0.76 [95% CI 0.65 - 0.89]) and a 16% reduction in all-cause mortality (HR 0.84 [95% CI 0.75 - 0.94]) in statin new users age 75-84 years. No significant difference in ASCVD risk or all-cause mortality was seen in subjects with diabetes and age ≥85 years.    

Conclusions: In participants age 75 years and older, statin use did not confer a reduction in ASCVD or all-cause mortality. In those with type 2 diabetes and age 75-84 years, statin use significantly decreased the incidence of ASCVD and mortality; however, this benefit was not seen in patients age 85 years and older. Of note, the trial involved older patients initiated on statins, thus data may not apply to patients continuing statin therapy that was initiated at a younger age. Further, the authors note that LDL cholesterol was low at baseline in patients with diabetes (ranging from 54 to 66 mg/dL among subgroups). Thus, study results bring to question potential for harm in treating to very low LDL levels. In addition, the trial population primarily consisted of those living in Spain, thus potential differences in other ethnic groups should be considered.

Key Points: Regarding primary prevention in older patients, initiating a statin may provide ASCVD and mortality benefit for those age 75-84 years with type 2 diabetes. Initiating a statin in patients without diabetes age 75 years and older or in patients with diabetes age 85 years and older is unlikely to provide cardiovascular or mortality benefit. Overall, shared decision making between patient and care team is essential any time statin therapy is considered in an older patient.  

Reference:

1. Ramos R, Comas-Cufi M, Marti-Lluch, et al. Statin for primary prevention of cardiovascular events and mortality in old and very old adults with and without type 2 diabetes: retrospective cohort study[published online September 5, 2018]. Br Med J. doi.10.1136/bmj.k3359.