Statins for primary prevention in the old and very old: Effective and safe

Statins are effective for primary prevention of cardiovascular disease (CVD) and all-cause mortality in individuals aged 75–84 and ≥85 years, and are not associated with significantly increased risks of myopathies and liver dysfunction, according to a target trial emulation conducted using real-world territory-wide electronic health records in Hong Kong.

Consensus is lacking in international guidelines on the use of statins for primary prevention in adults ≥75 years of age due to under-representation of this population in randomized controlled trials (RCTs). Researchers from the University of Hong Kong (HKU) and Harvard T. H. Chan School of Public Health therefore used real-world electronic health records from the Hospital Authority for sequential target trial emulation to evaluate the benefits and risks associated with using statins for primary prevention in this elderly population. [Ann Intern Med 2024;177:701-710]

The study included 42,680 matched person-trials aged 75–84 years and 5,390 matched person-trials aged ≥85 years who met indications for statin initiation (ie, LDL-cholesterol [LDL-C] level ≥4.1 mmol/L [160 mg/dL], or LDL-C level ≥3.4 mmol/L [130 mg/dL] with ≥2 CVD risk factors, or LDL-C level ≥2.6 mmol/L [100 mg/dL] with coronary heart disease risk equivalents) between January 2008 and December 2015. Adults 60–75 years of age (146,854 person-trials) served as benchmark to test the validity of the emulated trial due to the well-established effect of statin therapy in this population. Propensity score matching was used to emulate randomization of eligible person-trials at baseline, with statin initiators and noninitiators matched in a 1:1 ratio within each age group.

In those 60–75 years of age, estimated risk reduction in overall incidence of CVD (ie, a composite of myocardial infarction, heart failure and stroke) associated with statin initiation vs noninitiation was consistent with previous RCT results (hazard ratio [HR] in per-protocol [PP] analysis, 0.77; 95 percent confidence interval [CI], 0.72–0.83), demonstrating validity of the analytic approach and quality of the database.

Over an average follow-up of 5.3 years, PP analysis showed an estimated relative risk reduction (RRR) of 21 percent (HR, 0.79; 95 percent CI, 0.68–0.93) in overall CVD incidence among statin initiators vs noninitiators 75–84 years of age, while the estimated 5-year standardized absolute risk reduction (ARR) was 5 percent. For all-cause mortality, estimated RRR and 5-year standardized ARR were 14 percent (HR, 0.86; 95 percent CI, 0.78–0.95) and 1.38 percent, respectively.

In those ≥85 years of age, statin initiation was associated with an estimated 35 percent RRR in overall CVD incidence vs noninitiation (HR, 0.65; 95 percent CI, 0.55–0.76), while the estimated 5-year standardized ARR was 12.5 percent. Respective estimated RRR and 5-year standardized ARR for all-cause mortality were 25 percent (HR, 0.75; 95 percent CI, 0.63–0.89) and 6.85 percent.

No significantly increased risks of major adverse events, namely, myopathies or liver dysfunction, were found in either age group.

“[Of note,] the observed benefits of statin therapy remained substantial among the population aged ≥85 years. No evidence of severe adverse effects was identified with statin use in this population,” the researchers pointed out.

“Considering the increasing burden related to CVD in the ageing population, our study results support prescription of statin therapy for primary prevention of CVD in old and very old adults,” they concluded.