Regression discontinuity design to evaluate the effect of statins on myocardial infarction in electronic health records

Regression discontinuity design (RDD) is a quasi-experimental method intended for causal inference in observational settings. While RDD is gaining popularity in clinical studies, there are limited real-world studies examining the performance of this approach on estimating known trial-established casual effects. The goal of this paper is to estimate the effects of statins on myocardial infarction (MI) using RDD and propensity score matching. For the regression discontinuity analysis, we leveraged a 2008 guideline in the UK that recommends statins if a patient’s 10-year cardiovascular disease (CVD) risk score >20%. We used UK electronic health record data from the Health Improvement Network on 49,242 patients aged 65+ in 2008-2011 (our study baseline) without a history of CVD and no statin use in the year prior to the CVD risk score assessment. Both the regression discontinuity (n=19,432) and the propensity score matched populations (n=24,814) demonstrated good balance of confounders. Using RDD, the adjusted point estimate for statins on MI was in the protective direction and similar to the statin effect observed in clinical trials, although the confidence interval included the null (HR= 0.8, 95%CI: 0.4, 1.4). Conversely, the adjusted estimates using propensity score matching remained in the harmful direction: HR =2.4 (95%CI:2.0, 3.0). Regression discontinuity appeared superior to propensity score matching in replicating the known protective association of statins with MI, although precision was poor. Our findings suggest that, when used appropriately, regression discontinuity can expand the scope of clinical investigations aimed at causal inference by leveraging treatment rules from everyday clinical practice.