Statin use and outcome risks according to predicted CVD risk in Korea: A retrospective cohort study

Abstract

Background: The validity of cardiovascular disease (CVD) risk calculators in decision for statin therapy has not been fully evaluated at a population level. This study aimed to examine the net benefits of statins according to predicted CVD risk.

Methods and findings: A cohort of 40 to 79-year-old Korean adults without CVD was generated from the National Health Information Database 2006-2017. Major CVD event rates and all-cause mortality in 58,265 users who initiated statins during 2007-2010 were compared with those in 58,265 nonusers matched on propensity scores, from January 1, 2012 through December 31, 2017. Additionally, simulation was performed for the population-based cohort of 659,759 adults. CVD risk was predicted using the 2018 revised Pooled Cohort Equations. In propensity score-matched cohort, the CVD hazard ratios (95% CIs) in occasional, intermittent, and regular statin users were 1.06 (0.93-1.20), 0.82 (0.70-0.97), and 0.57 (0.50-0.64), respectively. The corresponding mortality hazard ratios were 1.01 (0.92-1.10), 0.87 (0.78-0.98), and 0.71 (0.66-0.77), respectively. In stratified analyses, the relative risk reductions were similar, irrespective of age, sex, or predicted CVD risk. Accordingly, absolute risk reductions were greater in higher risk categories. In 6-year follow-up simulation cohorts, regular statin use could reduce 17 CVDs and 28 deaths in 1000 adults with a 10-year risk of ≥10.0% vs 10 CVDs and 14 deaths in 1000 with ≥2 major risk factors. However, in actual adults with a risk of ≥10%, statin use was insufficient and estimated to reduce 3 CVDs and 4 deaths in 1000. Limitations of this study include assessment of medication use based on the prescription data, lack of information on the intensity of statins, and limited generalizability to individuals with very old age or other ethnicity.

Conclusions: CVD risk calculators were valid in decision-making for primary prevention statin therapy. Proper risk assessment and regular statin use in patients at high predicted risk would reduce outcome risks much more than present in Asian populations.

Fig 1. Flow chart of participant selection.

Fig 2. Hazard ratios for outcomes according to statin use status in the propensity score-matched cohort.

Among 58,265 pairs matched on propensity scores, multivariable-adjusted hazard ratios were estimated using Cox models with a time-varying covariate for statin use status. Baseline nonusers served as the reference. The participants who were diagnosed with cataract (or dementia, or diabetes) before the baseline were excluded from the analysis of cataract (or dementia, or diabetes). CVD, cardiovascular disease; ESKD, end-stage kidney disease.

Fig 3. Hazard ratios for outcomes according to statin use status within baseline statin users.

Within 61,665 statin users, multivariable-adjusted hazard ratios were estimated using Cox models with a time-varying covariate for statin use status. Occasional users served as the reference. The participants who were diagnosed with cataract (or dementia, or diabetes) before the baseline were excluded from the analysis of cataract (or dementia, or diabetes). CVD, cardiovascular disease; ESKD, end-stage kidney disease.

Fig 4. Hazard ratios for primary outcomes in stratified analyses.

Multivariable-adjusted hazard ratios were estimated using Cox models with a time-varying covariate for statin use status, in subgroups stratified by age, sex, or 10-year CVD risk. CVD, cardiovascular disease.

Fig 5. Simulation for the Korean population with no prior CVD.

The numbers of events in simulated regular statin users were estimated on the assumption that the relative risk reductions of 43.3% for CVD and 28.8% for mortality were not different between the simulated and propensity score-matched cohorts, nor were they different among the CVD risk categories. CVD, cardiovascular disease.

Fig 6. Hazard ratios for CVD according to predicted risk scores.

Among propensity score-matched statin users (A) and nonusers (B), unadjusted hazard ratios (solid line) and 95% CIs (dotted line) were estimated using a restricted cubic spline function with five knots placed at the 5th, 25th, 50th, 75th, and 95th percentile CVD risk scores. CVD, cardiovascular disease.