Background: Regression discontinuity is gaining popularity in epidemiologic studies aimed at causal inference from observational data, but there are limited real-world studies comparing this approach to potential outcomes methods.
Methods: In this methodologic investigation, we estimate the causal effect of statins on myocardial infarction (MI), a positive control outcome, using regression discontinuity and propensity score matching. For the regression discontinuity analysis, we leveraged a 2008 UK guideline that recommends statins if a patient's 10-year cardiovascular disease (CVD) risk score >20%. We used electronic health record data (2008-2018) from the Health Improvement Network (THIN) on 49,242 patients aged 65 and older in the UK without a history of CVD and no statin use in the year prior to the CVD risk score assessment. Outcomes were defined using Read codes and censored at 10 years; 10-year CVD risk was assessed primarily (81.8%) using the 1991 Framingham risk score.
Results: In sex and age adjusted analyses, the estimate for statin use on MI was HR = 2.69 (95% CI: 2.28, 3.17). Both the regression discontinuity (n=19,432) and the propensity score matched populations (n=24,814) demonstrated good balance of confounders. Using regression discontinuity, the adjusted point estimate for statins on MI was in the protective direction, although the confidence interval included the null (HR: 0.79, 95% CI: 0.44, 1.44). Conversely, the adjusted estimates using propensity score matching remained in the harmful direction: HR = 2.41 (95% CI: 1.96, 2.99).
Conclusion: Regression discontinuity appeared superior to propensity score matching in estimation of the known protective association of statins with MI, although precision was poor. A strength of regression discontinuity is that it can better account for bias due to unmeasured confounders than matching, which is of key importance in observational studies aimed at causal inference.