Statin Therapy for Primary Prevention in US Veterans 75 Years and Older

Statin Therapy for Primary Prevention in US Veterans 75 Years and Older
Paige Behrend, Pharm.D., Park Nicollet

Background: Adults 75 years and older are currently the fastest-growing segment of the population, and life tables estimate that those who have reached age 80 will live on average eight to nine additional years. Additionally, incidence and prevalence of atherosclerotic cardiovascular disease (ASCVD) rises with age and remains the leading cause of death in the United States. However, patients 75 years and older are frequently excluded from clinical trials that would otherwise provide guidance on statin therapy in this population. The current stance per the 2019 ACC/AHA cholesterol guidelines is that it may be reasonable to initiate statin therapy for primary prevention in adults 75 years and older, provided that the patient does not have a life-limiting disease.

Purpose: The objective of this study was to evaluate the role of new statin use in mortality and primary prevention of ASCVD in veterans 75 years and older. 

Study Design: The study design was a retrospective cohort study, using electronic Veterans Health Association (VHA) health record data. Patients were eligible for inclusion in the study if they were at least 75 years of age, received regular care for at least two years through the VHA from 2002 to 2012, and were not already on statin therapy for primary ASCVD prevention. Notably, those with cancer, dementia, or paralysis were not excluded from this study in order to create a cohort of patients that resembles clinical practice. Exclusion criteria included any history of statin use, prior ASCVD events, missing demographic data, or death in the first 150 days from baseline. The primary outcomes were all-cause and cardiovascular mortality. Secondary outcomes included MI, ischemic stroke, revascularization with CABG or PCI, and a composite of these events. Follow-up time was measured from date of entry into the study cohort to date of death in the treatment group, or initiation of statin for primary prevention in the control group. Because time to benefit for statins begins two to five years after initiation, sensitivity analysis hazard ratios were determined at two years from the statin start date. 

Results: Statin use was associated with a significantly lower risk of all-cause mortality (HR 0.75 [95% CI 0.74 – 0.76]) and cardiovascular death (HR 0.8 [95% CI 0.78 – 0.81]) across all age groups, including those 90 years and older. Notably, there was a significant difference for the primary outcome in patients with dementia (P<0.05) but no significant differences according to race, sex, or diabetes status. The mean age of participants was 81.1 years, 97.3% of the study population were men, and 91% were white. Simvastatin was the most commonly prescribed statin (84.8%). The mean follow-up time was 6.8 years. The secondary outcome was statistically significant for three subgroups: composite ASCVD in those with prior dementia vs. those without prior dementia (P=0.02), ischemic stroke according to race (white: HR 0.99 [95% CI 0.97 – 1.02]; black: HR 0.85 [95% CI 0.77 – 0.93]), and revascularization according to age (P=0.01).  

Conclusions: New statin use among veterans 75 years and older was associated with significantly lower risk of all-cause and cardiovascular mortality, even in those with advanced age and other comorbidities.  These results suggest that age alone should not be a determinant for starting or stopping a statin. Additionally, there was no significant difference in the primary outcome according to race, sex, or diabetes status which suggests that an even broader population within this generation of patients may benefit from statin therapy. A limitation of this study is that adverse effects such as myalgias, postulated decline in cognition, drug-drug interactions, and polypharmacy were not assessed and these factors may be significant in deciding whether to start, stop, or continue statin therapy for an older adult. Ultimately, further research is needed to better define the role of new statin therapy for primary prevention in patients 75 years and older.

Key Point: Among U.S. veterans 75 years and older without atherosclerotic cardiovascular disease at baseline, new statin use was associated with a significantly lower risk of all-cause and cardiovascular mortality. 

Reference:

  1. Orkaby A, Driver J, Ho Y, et al. Association of Statin Use With All-Cause and Cardiovascular Mortality in US Veterans 75 Years and Older. JAMA. 2020;324(1):68-78.