Systematically exploring repurposing effects of antihypertensives

Abstract

With availability of voluminous sets of observational data, an empirical paradigm to screen for drug repurposing opportunities (i.e., beneficial effects of drugs on nonindicated outcomes) is feasible. In this article, we use a linked claims and electronic health record database to comprehensively explore repurposing effects of antihypertensive drugs. We follow a target trial emulation framework for causal inference to emulate randomized controlled trials estimating confounding adjusted effects of antihypertensives on each of 262 outcomes of interest. We then fit hierarchical models to the results as a form of postprocessing to account for multiple comparisons and to sift through the results in a principled way. Our motivation is twofold. We seek both to surface genuinely intriguing drug repurposing opportunities and to elucidate through a real application some study design decisions and potential biases that arise in this context.

Keywords: antihypertensives; causal inference; drug repurposing; hierarchical models.

FIGURE 1

Comparative effectiveness results of the antihypertensive treatments for A, heart failure, B, acute myocardial infarction, C, ischemic stroke, D, hemorrhagic stroke, and E, cardiac dysrhythmias. The cumulative incidence rate is measured at 1 year after baseline. The results use the single outcome pooling method